Most Cited by Mini-Reviews in Medicinal Chemistry MRMC
Mini-Reviews in Medicinal Chemistry MRMC
Modern research in drug discovery from medicinal plants involves a multidimensional approach comb... more Modern research in drug discovery from medicinal plants involves a multidimensional approach combining botanical, phytochemical, biochemical combinatorial chemistry and bioassay-guided fractionation approaches. Natural sources continue to provide an alternative as pharmacological leads against various devastating diseases such as diabetes, CVD, cancer etc. Nowadays, there is enormous requirement of safe and effective drugs in the world. This has prompted scientists to revert back towards natural resources as a potential source of therapeutics for treatment and management of such chronic and fatal diseases. However, there are certain serious challenges and limitations in this field including scale up and commercialization of active compounds which allow only one in thousand lead molecules to be developed as drug. A systematic and scientific approach is an essential requirement for drug development from natural resource. This mini review provides an overview of the methods involved in natural product research starting from crude plant extract to bioactive pharmacological lead. Moreover, it also discusses the limitations of working concerning the bioactivity of medicinal plants.
Mini-Reviews in Medicinal Chemistry
Chalcones (1, 3-Diphenyl-2-propen-1-one) are constituted by a three carbon α, β-unsaturated carbo... more Chalcones (1, 3-Diphenyl-2-propen-1-one) are constituted by a three carbon α, β-unsaturated carbonyl system. The biosynthesis of flavonoids and isoflavonoids is initiated by chalcones. Notable pharmacological activities of chalcones and its derivatives include anti-inflammatory, antifungal, antibacterial, antimalarial, antituberculosis, antitumor, antimicrobial and antiviral effects respectively. Owing to simplicity of the chemical structures and a huge variety of pharmacological actions exhibited, the entities derived from chalcones are subjected to extensive consideration. This review article is an effort to sum up the anti-inflammatory activities of chalcone derived chemical entities. Effect of chalcones on lipid peroxidation, heme oxygenase 1(HO-1), cyclooxygenase (COX), interleukin 5 (IL-5), nitric oxide (NO) and expression of cell adhesion molecules (CAM) is summarized stepwise.
Mini-Reviews in Medicinal Chemistry
Candida albicans can invade humans and may lead to mucosal and skin infections or to deep-seated ... more Candida albicans can invade humans and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients. In this context, both the host immune status and the ability of C. albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance; in this last case, culminating in the establishment of successful infection known as candidiasis. C. albicans possesses a potent armamentarium consisting of several virulence molecules that help the fungal cells to escape from the host immune responses. There is no doubt that the secretion of aspartic proteases, designated as Saps, is one of the major virulence attributes produced by C. albicans cells, since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions. For these reasons, Saps clearly hold promise as new potential drug targets. Corroborating this hypothesis, the introduction of anti-human immunodeficiency virus drugs of the aspartic protease inhibitor-type (HIV PIs) have emerged as new agents for the inhibition of Saps. The introduction of HIV PIs has revolutionized the treatment of HIV disease, reducing the opportunistic infections, especially candidiasis. The attenuation of candidal infections in HIV-infected individuals might not solely has not only resulted from improved immunological status, but also as a result of direct inhibition of C. albicans Saps as well as the blockage of several biological processes controlled by these proteolytic enzymes. The present article will discuss the updates on the functional implications of HIV PIs on the development of candidiasis.
Removal of toxic metals and toxins using microbial biomass has been introduced as an inexpensive,... more Removal of toxic metals and toxins using microbial biomass has been introduced as an inexpensive, new
promising method on top of conventional methods for decontamination of food, raw material and concentrated. In this
article the potential application of lactic acid bacteria and yeasts as the most familiar probiotics to eliminate, inactivate or
reduce bioavailability of contamination in foods and feed has been reviewed. After fast glance to beneficial health effects
and preservative properties of lactic acid bacteria, the mechanisms which explain antibacterial and antifungal efficiency as
well as their antifungal metabolites are mentioned. Then the article has been focused on potential application of single
strain or combination of lactic acid bacteria for removal of heavy metals (copper, lead, cadmium, chromium, arsenic),
cyanotoxins (microcystin-LR, -RR, -LF) and mycotoxins (aflatoxin B1, B2, B2a, M1, M2, G1, G2, patulin, ochratoxin A,
deoxynivalenol, fumonisin B1 and B2, 3-acetyldeoxynivalenol, deoxynivalenol, fusarenon, nivalenol, diacetoxyscirpenol,
HT-2 and T-2 toxin, zearalenone and its derivative, etc) from aqueous solutions in vitro. Wherever possible the
mechanism of decontamination and the factors influencing yield of removal are discussed. Some factors which can
facilitate metal removal capacity of lactic acid bacteria including the strains, surface charge, pH, temperature, presence of
other cations are introduced. The cell wall structure of lactic acid bacteria and yeasts are also introduced for further
explanation of mechanism of action in complex binding of probiotic to contaminants and strength of mycotoxin–
bacterium interaction.
1,2,3-Triazine is an interesting class of heterocyclic compounds. Various synthetic analogs of 1,... more 1,2,3-Triazine is an interesting class of heterocyclic compounds. Various synthetic analogs of 1,2,3-triazine
have been prepared and evaluated for many pharmacological activities in different models with desired findings. Some
analogs have shown potent pharmacological activity and may be considered as lead molecule for the development of
future drugs. This review is an attempt to organize the chemical and pharmacological aspects of 1,2,3-triazine analogs
reported till date systematically since 1970.
Phencyclidine (PCP, I) and many of its derivatives have demonstrated many pharmacological effects... more Phencyclidine (PCP, I) and many of its derivatives have demonstrated many pharmacological effects. They
interact with a number of neurotransmitter systems within the central nervous system. For example, Phencyclidine is a
noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, and it causes the
release and inhibits the reuptake of monoaminergic neurotransmitters, including dopamine, serotonin and norepinephrine.
In this study, new thienyl (TCP, II), as well as benzothiophen (BTCP, III) derivatives (IV-VII) were synthesized. The
acute and chronic pain activities of these drugs were studied using the tail immersion and formalin tests on mice and the
results were compared with PCP, TCP and control groups at dosage of 10 mg/kg. The results indicated that the drug VII
produced more analgesic effects on acute chemical pain in formalin test compared with other drugs. In addition, this
analgesic effect was remarkably seen for drugs II, VI and VII in chronic pain in the mentioned test in comparison with
other drugs. Also, the results showed that acute thermal pain could be diminished by drugs VI, II and I compared with
other drugs in tail immersion test. It can be concluded that more analgesic effects of new BTCP analogues (VI and VII)
may be concerned with antinociception activities of benzothiophene group and also with binding to cocaine site on the
dopamine transporter receptor which seems to be more potent than PCP receptor in decreasing pain.
As an important part of non steroids anti-inflammation drug (NSAIDs), salicylate has developed fr... more As an important part of non steroids anti-inflammation drug (NSAIDs), salicylate has developed from natural
substance salicylic acid to natrium salicylicum, to aspirin. Now, methyl salicylate glycoside, a new derivative of salicylic
acid, is modified with a -COOH group integrated one methyl radical into formic ether, and a -OH linked with a
monosaccharide, a disaccharide or a trisaccharide unit by glycosidic linkage. It has the similar pharmacological activities,
anti-inflammatory, analgesic, antipyretic and antithrombotic as the previous salicylates’ without resulting in serious side
effects, particularly the gastrointestinal toxicity. Owing to the superiority of those significant bioactivities, methyl
salicylate glycosides have became a hot research area in NSAIDs for several years. This paper compiles all 9 naturally
occurring methyl salicylate glycosides, their distribution of the resource and pharmacological mechanism, which could
contribute to the new drug discovery
The quantitative structure activity relationship (QSAR) study is the most cited and reliable comp... more The quantitative structure activity relationship (QSAR) study is the most cited and reliable computational
technique used for decades to obtain information about a substituent’s physicochemical property and biological activity.
There is step-by-step development in the concept of QSAR from 0D to 2D. These models suffer various limitations that
led to the development of 3D-QSAR. There are large numbers of literatures available on the utility of 3D-QSAR for drug
design. Three-dimensional properties of molecules with non-covalent interactions are served as important tool in the selection
of bioactive confirmation of compounds. With this view, 3D-QSAR has been explored with different advancements like
COMFA, COMSA, COMMA, etc. Some reports are also available highlighting the limitations of 3D-QSAR. In a way, to
overcome the limitations of 3D-QSAR, more advanced QSAR approaches like 4D, 5D and 6D-QSAR have been evolved.
Here, in this present review we have focused more on the present and future of more predictive models of QSAR studies.
The review highlights the basics of 3D to 6D-QSAR and mainly emphasizes the advantages of one dimension over the
other. It covers almost all recent reports of all these multidimensional QSAR approaches which are new paradigms in drug
discovery.
Resistance towards chemotherapy and radiotherapy as well as relapse of cancer is the major obstac... more Resistance towards chemotherapy and radiotherapy as well as relapse of cancer is the major obstacle in the
treatment of cancer. The main factor behind is cancer stem cells (CSCs) which are more resistant to conventional
chemotherapy, radiotherapy and are quite able to regenerate whole new tumor again if remain alive during treatment.
Targeting CSCs along with actively dividing cancer cells may significantly contribute to the solution of the problem of
resistance and relapse. Various approaches are implemented to eradicate CSCs which include CSC markers specific
compounds, Drugs which disturb niche and various inhibitors/modulators of signaling pathways. Hedgehog (Hh), Wnt
and Notch pathways are modulated/inhibited using various agents and shown beneficial results in multiple forms of
cancer. Many inhibitors/modulators of these pathways have been entered in the clinical trials. MicroRNAs have also been
developed as anti CSCs agents. In this review, we have covered current status of CSC targeting therapy based on CSC
markers, CSC niche, Hedgehog, Wnt, Notch pathway along with MicroRNA based targeting strategies and possibility of
implementation multi-targeted anti-CSC therapy for the better outcome of the results.
Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder, with a dramat... more Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder, with a dramatic socioeconomic
impact. The progress of AD is characterized by a severe loss in memory and cognition, leading to behavioral
changing, depression and death. During the last decades, only a few anticholinergic drugs were launched in the market,
mainly acetylcholinesterase inhibitors (AChEIs), with indications for the treatment of initial and moderate stages of AD.
The search for new AChEIs, capable to overcome the limitations observed for rivastigmine and tacrine, led Sugimoto and
co-workers to the discovery of donepezil. Besides its high potency, donepezil also exhibited high selectivity for AChE and
a very low toxicity. In this review, we discuss the main structural and pharmacological attributes that have made
donepezil the first choice medicine for AD, and a versatile structural model for the design of novel AChEIs, in spite of
multipotent and multitarget-directed ligands. Many recent data from literature transdue great efforts worldwide to produce
modifications in the donepezil structure that could result in new bioactive chemical entities with innovative structural
pattern. Furthermore, multi-potent ligands have also been designed by molecular hybridization, affording rivastigmine-,
tacrine- and huperzine-donepezil potent and selective AChEIs. In a more recent strategy, structural features of donepezil
have been used as a model to design multitarget-directed ligands, aiming at the discovery of new effective drug candidates
that could exhibit concomitant pharmacological activities as dual or multi- enzymatic inhibitors as genuine innovative
therapeutic alternatives for the treatment of AD.
Chinese Herbal Medicines (CHM) have been used in disease prevention and treatment for centuries i... more Chinese Herbal Medicines (CHM) have been used in disease prevention and treatment for centuries in China. A
number of anti-breast cancer agents isolated from CHM recently, showed very interesting structures, although some of the
mechanism of action is not quite clear. These unique chemical structures could be an important information resource for
new anti-breast cancer drugs’ design and discovery. This review summarizes these findings on anti-breast cancer agents
from CHM.
Inflammatory diseases including, different types of rheumatic diseases are the major problems ass... more Inflammatory diseases including, different types of rheumatic diseases are the major problems associated with
the presently available non-steroidal anti-inflammatory agents. The numbers of plant derived drugs have been screened for
their anti-inflammatory and anti-arthritic activity. Drug development in the recent times often relies on use of natural and
synthetic drugs, which are promising candidates as therapeutic agents for prevention of diseases and disorders. These
drugs possess different chemical structures, with wide range of therapeutic activities. The mechanism of Inflammation
mainly involve in development of serious diseases, such as cancer, rheumatoid arthritis, sprains, bronchitis, muscle pains,
chronic inflammatory bowel disease, persistent asthma, and liver fibrosis. Development of inflammatory events basically
related to various chemicals, such as glucocorticoids (GCs) and mometasone furoate (MF); endogenous factors such as
tumor necrosis factor alpha (TNF- ); enzymes and proteins such as copper and zinc-superoxide dismutase (SOD), proinflammatory
peptide substance (PPS), RGD peptides, interleukin-4 (IL-4), IL-10, interferon- (IFN- ), COX, LOX,
cytokines such as interleukin-1 (IL-1); reactive oxygen species (ROS), nitric oxide (NO) and prostaglandin E2; as well as
pro-inflammatory cells such as T and NK cells are well known to have an important role. Based on these correlations,
numerous assays were used for inflammatory mechanism research, which was described in this paper.
Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacol... more Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacology
treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been
described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last
decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial
and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and
advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.
This article presents the potential of PLGA nanoparticles for the oral administration of drugs. D... more This article presents the potential of PLGA nanoparticles for the oral administration of drugs. Different
strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of
nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing
hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic
moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are
employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral
bioavailability, the mechanism of each additive.
Histamine H3 receptors are found mostly in central nervous system involved in the regulation of r... more Histamine H3 receptors are found mostly in central nervous system involved in the regulation of release of
various neurotransmitters in brain. They have been implicated in diverse potential therapeutic applications such as sleepwake
disorders, attention-deficient hyperactivity disorder, epilepsy, cognitive impairment and obesity. This review is an
attempt to elucidate the function of H3 receptors and their role in various CNS disorders. Also, it is aimed at collating the
information on efforts of various medicinal chemists to synthesize the H3 receptor agonists and antagonists in single
article.
During the past 40 years, somatostatin (SST) has been a subject of intensive research. Apart from... more During the past 40 years, somatostatin (SST) has been a subject of intensive research. Apart from its substantial
role in the neuroendocrine system, due to its dense localization in various areas in the brain, its functions as a
neuromodulator have also been thoroughly investigated. Increasing evidence suggests that SST plays a crucial role in
memory and cognition. Synthetic forms, biologically active peptide sequences, SST receptor agonists and SST depleting
agents have been applied in animal models and in human studies of a number of neuropsychiatric disorders. The
translation of experimental data into clinical use could provide novel therapies in neurodegenerative disorders involving
cognitive dysfunctions. However in view of the controversial data reported concerning the different roles of the SST
receptor subtypes, and the lack of SST analogs that are able to cross diffusion barriers and act selectively at these receptor
subtypes, broader clinical use of SST analogs as cognitive enhancers is limited. This review covers the whole range of
available experimental results relating to the behavioral effects of SST, and highlights the potential for further
investigations
Open Access by Mini-Reviews in Medicinal Chemistry MRMC
Amaryllidaceae alkaloids are extensively studied for their biological activities in several pharm... more Amaryllidaceae alkaloids are extensively studied for their biological activities in several pharmaceutical areas, including, for example, Alzheimers disease for which galanthamine has already reached the market. Among this chemical family, lycorine displays very promising anti-tumor properties. This review first focuses on the chemical diversity of natural and synthetic analogues of lycorine and their metabolites, and then on mechanisms of action and biological targets through which lycorine and its derivatives display their anti-tumor activity. Our analysis of the structure-activity relationships of this family of compounds highlights the existence of various potential leads for the development of novel anticancer agents.
Many therapeutic reagents for hepatitis B virus infection have established efficacy in goals such... more Many therapeutic reagents for hepatitis B virus infection have established efficacy in goals such as alanine aminotransferase normalization, hepatitis B virus DNA suppression, HBeAg seroconversion, histological improvement, and reduce disease progression. However, it is not established that the efficacy of these reagents for the long-term survival and prevention of hepatocellular carcinoma although recent meta-analyses have also shown antiviral therapy to be efficacious. This article reviews the current status and innovative new options for antiviral therapy for hepatitis B and also discusses the various mechanisms of action for each drug, the results of clinical studies for each therapy, and the problems yet to be solved with respect to hepatitis B treatment.
Different data show that circulating lymphocytes possess functional serotonin and dopamine transp... more Different data show that circulating lymphocytes possess functional serotonin and dopamine transporters (SERT and DAT, respectively). This papers aims to review most of the available literature on this topic, while highlighting the possible role of SERT and DAT, as well as that of their substrates including antidepressants on the immune system.
Vascular endothelial growth factor receptor (VEGFR) is an important receptor tyrosine kinase (RTK... more Vascular endothelial growth factor receptor (VEGFR) is an important receptor tyrosine kinase (RTK) in the induction of angiogenesis. Abnormal activation of VEGFR leads to several disorders including cancer. Nowadays, inhibition of VEGFR kinase has been one of the most powerful clinical strategies in cancer treatment and great efforts to design and synthesize small molecular VEGFR inhibitors for cancer research have been made in recent years. This review highlights the major progress and development of them, including their structure and pharmacophore features, biological activities and structure-activity relationships (SAR). Special attentions are paid to the compounds available in market or in advanced clinical stages.
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Most Cited by Mini-Reviews in Medicinal Chemistry MRMC
promising method on top of conventional methods for decontamination of food, raw material and concentrated. In this
article the potential application of lactic acid bacteria and yeasts as the most familiar probiotics to eliminate, inactivate or
reduce bioavailability of contamination in foods and feed has been reviewed. After fast glance to beneficial health effects
and preservative properties of lactic acid bacteria, the mechanisms which explain antibacterial and antifungal efficiency as
well as their antifungal metabolites are mentioned. Then the article has been focused on potential application of single
strain or combination of lactic acid bacteria for removal of heavy metals (copper, lead, cadmium, chromium, arsenic),
cyanotoxins (microcystin-LR, -RR, -LF) and mycotoxins (aflatoxin B1, B2, B2a, M1, M2, G1, G2, patulin, ochratoxin A,
deoxynivalenol, fumonisin B1 and B2, 3-acetyldeoxynivalenol, deoxynivalenol, fusarenon, nivalenol, diacetoxyscirpenol,
HT-2 and T-2 toxin, zearalenone and its derivative, etc) from aqueous solutions in vitro. Wherever possible the
mechanism of decontamination and the factors influencing yield of removal are discussed. Some factors which can
facilitate metal removal capacity of lactic acid bacteria including the strains, surface charge, pH, temperature, presence of
other cations are introduced. The cell wall structure of lactic acid bacteria and yeasts are also introduced for further
explanation of mechanism of action in complex binding of probiotic to contaminants and strength of mycotoxin–
bacterium interaction.
have been prepared and evaluated for many pharmacological activities in different models with desired findings. Some
analogs have shown potent pharmacological activity and may be considered as lead molecule for the development of
future drugs. This review is an attempt to organize the chemical and pharmacological aspects of 1,2,3-triazine analogs
reported till date systematically since 1970.
interact with a number of neurotransmitter systems within the central nervous system. For example, Phencyclidine is a
noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, and it causes the
release and inhibits the reuptake of monoaminergic neurotransmitters, including dopamine, serotonin and norepinephrine.
In this study, new thienyl (TCP, II), as well as benzothiophen (BTCP, III) derivatives (IV-VII) were synthesized. The
acute and chronic pain activities of these drugs were studied using the tail immersion and formalin tests on mice and the
results were compared with PCP, TCP and control groups at dosage of 10 mg/kg. The results indicated that the drug VII
produced more analgesic effects on acute chemical pain in formalin test compared with other drugs. In addition, this
analgesic effect was remarkably seen for drugs II, VI and VII in chronic pain in the mentioned test in comparison with
other drugs. Also, the results showed that acute thermal pain could be diminished by drugs VI, II and I compared with
other drugs in tail immersion test. It can be concluded that more analgesic effects of new BTCP analogues (VI and VII)
may be concerned with antinociception activities of benzothiophene group and also with binding to cocaine site on the
dopamine transporter receptor which seems to be more potent than PCP receptor in decreasing pain.
substance salicylic acid to natrium salicylicum, to aspirin. Now, methyl salicylate glycoside, a new derivative of salicylic
acid, is modified with a -COOH group integrated one methyl radical into formic ether, and a -OH linked with a
monosaccharide, a disaccharide or a trisaccharide unit by glycosidic linkage. It has the similar pharmacological activities,
anti-inflammatory, analgesic, antipyretic and antithrombotic as the previous salicylates’ without resulting in serious side
effects, particularly the gastrointestinal toxicity. Owing to the superiority of those significant bioactivities, methyl
salicylate glycosides have became a hot research area in NSAIDs for several years. This paper compiles all 9 naturally
occurring methyl salicylate glycosides, their distribution of the resource and pharmacological mechanism, which could
contribute to the new drug discovery
technique used for decades to obtain information about a substituent’s physicochemical property and biological activity.
There is step-by-step development in the concept of QSAR from 0D to 2D. These models suffer various limitations that
led to the development of 3D-QSAR. There are large numbers of literatures available on the utility of 3D-QSAR for drug
design. Three-dimensional properties of molecules with non-covalent interactions are served as important tool in the selection
of bioactive confirmation of compounds. With this view, 3D-QSAR has been explored with different advancements like
COMFA, COMSA, COMMA, etc. Some reports are also available highlighting the limitations of 3D-QSAR. In a way, to
overcome the limitations of 3D-QSAR, more advanced QSAR approaches like 4D, 5D and 6D-QSAR have been evolved.
Here, in this present review we have focused more on the present and future of more predictive models of QSAR studies.
The review highlights the basics of 3D to 6D-QSAR and mainly emphasizes the advantages of one dimension over the
other. It covers almost all recent reports of all these multidimensional QSAR approaches which are new paradigms in drug
discovery.
treatment of cancer. The main factor behind is cancer stem cells (CSCs) which are more resistant to conventional
chemotherapy, radiotherapy and are quite able to regenerate whole new tumor again if remain alive during treatment.
Targeting CSCs along with actively dividing cancer cells may significantly contribute to the solution of the problem of
resistance and relapse. Various approaches are implemented to eradicate CSCs which include CSC markers specific
compounds, Drugs which disturb niche and various inhibitors/modulators of signaling pathways. Hedgehog (Hh), Wnt
and Notch pathways are modulated/inhibited using various agents and shown beneficial results in multiple forms of
cancer. Many inhibitors/modulators of these pathways have been entered in the clinical trials. MicroRNAs have also been
developed as anti CSCs agents. In this review, we have covered current status of CSC targeting therapy based on CSC
markers, CSC niche, Hedgehog, Wnt, Notch pathway along with MicroRNA based targeting strategies and possibility of
implementation multi-targeted anti-CSC therapy for the better outcome of the results.
impact. The progress of AD is characterized by a severe loss in memory and cognition, leading to behavioral
changing, depression and death. During the last decades, only a few anticholinergic drugs were launched in the market,
mainly acetylcholinesterase inhibitors (AChEIs), with indications for the treatment of initial and moderate stages of AD.
The search for new AChEIs, capable to overcome the limitations observed for rivastigmine and tacrine, led Sugimoto and
co-workers to the discovery of donepezil. Besides its high potency, donepezil also exhibited high selectivity for AChE and
a very low toxicity. In this review, we discuss the main structural and pharmacological attributes that have made
donepezil the first choice medicine for AD, and a versatile structural model for the design of novel AChEIs, in spite of
multipotent and multitarget-directed ligands. Many recent data from literature transdue great efforts worldwide to produce
modifications in the donepezil structure that could result in new bioactive chemical entities with innovative structural
pattern. Furthermore, multi-potent ligands have also been designed by molecular hybridization, affording rivastigmine-,
tacrine- and huperzine-donepezil potent and selective AChEIs. In a more recent strategy, structural features of donepezil
have been used as a model to design multitarget-directed ligands, aiming at the discovery of new effective drug candidates
that could exhibit concomitant pharmacological activities as dual or multi- enzymatic inhibitors as genuine innovative
therapeutic alternatives for the treatment of AD.
number of anti-breast cancer agents isolated from CHM recently, showed very interesting structures, although some of the
mechanism of action is not quite clear. These unique chemical structures could be an important information resource for
new anti-breast cancer drugs’ design and discovery. This review summarizes these findings on anti-breast cancer agents
from CHM.
the presently available non-steroidal anti-inflammatory agents. The numbers of plant derived drugs have been screened for
their anti-inflammatory and anti-arthritic activity. Drug development in the recent times often relies on use of natural and
synthetic drugs, which are promising candidates as therapeutic agents for prevention of diseases and disorders. These
drugs possess different chemical structures, with wide range of therapeutic activities. The mechanism of Inflammation
mainly involve in development of serious diseases, such as cancer, rheumatoid arthritis, sprains, bronchitis, muscle pains,
chronic inflammatory bowel disease, persistent asthma, and liver fibrosis. Development of inflammatory events basically
related to various chemicals, such as glucocorticoids (GCs) and mometasone furoate (MF); endogenous factors such as
tumor necrosis factor alpha (TNF- ); enzymes and proteins such as copper and zinc-superoxide dismutase (SOD), proinflammatory
peptide substance (PPS), RGD peptides, interleukin-4 (IL-4), IL-10, interferon- (IFN- ), COX, LOX,
cytokines such as interleukin-1 (IL-1); reactive oxygen species (ROS), nitric oxide (NO) and prostaglandin E2; as well as
pro-inflammatory cells such as T and NK cells are well known to have an important role. Based on these correlations,
numerous assays were used for inflammatory mechanism research, which was described in this paper.
treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been
described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last
decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial
and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and
advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.
strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of
nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing
hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic
moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are
employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral
bioavailability, the mechanism of each additive.
various neurotransmitters in brain. They have been implicated in diverse potential therapeutic applications such as sleepwake
disorders, attention-deficient hyperactivity disorder, epilepsy, cognitive impairment and obesity. This review is an
attempt to elucidate the function of H3 receptors and their role in various CNS disorders. Also, it is aimed at collating the
information on efforts of various medicinal chemists to synthesize the H3 receptor agonists and antagonists in single
article.
role in the neuroendocrine system, due to its dense localization in various areas in the brain, its functions as a
neuromodulator have also been thoroughly investigated. Increasing evidence suggests that SST plays a crucial role in
memory and cognition. Synthetic forms, biologically active peptide sequences, SST receptor agonists and SST depleting
agents have been applied in animal models and in human studies of a number of neuropsychiatric disorders. The
translation of experimental data into clinical use could provide novel therapies in neurodegenerative disorders involving
cognitive dysfunctions. However in view of the controversial data reported concerning the different roles of the SST
receptor subtypes, and the lack of SST analogs that are able to cross diffusion barriers and act selectively at these receptor
subtypes, broader clinical use of SST analogs as cognitive enhancers is limited. This review covers the whole range of
available experimental results relating to the behavioral effects of SST, and highlights the potential for further
investigations
Open Access by Mini-Reviews in Medicinal Chemistry MRMC
promising method on top of conventional methods for decontamination of food, raw material and concentrated. In this
article the potential application of lactic acid bacteria and yeasts as the most familiar probiotics to eliminate, inactivate or
reduce bioavailability of contamination in foods and feed has been reviewed. After fast glance to beneficial health effects
and preservative properties of lactic acid bacteria, the mechanisms which explain antibacterial and antifungal efficiency as
well as their antifungal metabolites are mentioned. Then the article has been focused on potential application of single
strain or combination of lactic acid bacteria for removal of heavy metals (copper, lead, cadmium, chromium, arsenic),
cyanotoxins (microcystin-LR, -RR, -LF) and mycotoxins (aflatoxin B1, B2, B2a, M1, M2, G1, G2, patulin, ochratoxin A,
deoxynivalenol, fumonisin B1 and B2, 3-acetyldeoxynivalenol, deoxynivalenol, fusarenon, nivalenol, diacetoxyscirpenol,
HT-2 and T-2 toxin, zearalenone and its derivative, etc) from aqueous solutions in vitro. Wherever possible the
mechanism of decontamination and the factors influencing yield of removal are discussed. Some factors which can
facilitate metal removal capacity of lactic acid bacteria including the strains, surface charge, pH, temperature, presence of
other cations are introduced. The cell wall structure of lactic acid bacteria and yeasts are also introduced for further
explanation of mechanism of action in complex binding of probiotic to contaminants and strength of mycotoxin–
bacterium interaction.
have been prepared and evaluated for many pharmacological activities in different models with desired findings. Some
analogs have shown potent pharmacological activity and may be considered as lead molecule for the development of
future drugs. This review is an attempt to organize the chemical and pharmacological aspects of 1,2,3-triazine analogs
reported till date systematically since 1970.
interact with a number of neurotransmitter systems within the central nervous system. For example, Phencyclidine is a
noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, and it causes the
release and inhibits the reuptake of monoaminergic neurotransmitters, including dopamine, serotonin and norepinephrine.
In this study, new thienyl (TCP, II), as well as benzothiophen (BTCP, III) derivatives (IV-VII) were synthesized. The
acute and chronic pain activities of these drugs were studied using the tail immersion and formalin tests on mice and the
results were compared with PCP, TCP and control groups at dosage of 10 mg/kg. The results indicated that the drug VII
produced more analgesic effects on acute chemical pain in formalin test compared with other drugs. In addition, this
analgesic effect was remarkably seen for drugs II, VI and VII in chronic pain in the mentioned test in comparison with
other drugs. Also, the results showed that acute thermal pain could be diminished by drugs VI, II and I compared with
other drugs in tail immersion test. It can be concluded that more analgesic effects of new BTCP analogues (VI and VII)
may be concerned with antinociception activities of benzothiophene group and also with binding to cocaine site on the
dopamine transporter receptor which seems to be more potent than PCP receptor in decreasing pain.
substance salicylic acid to natrium salicylicum, to aspirin. Now, methyl salicylate glycoside, a new derivative of salicylic
acid, is modified with a -COOH group integrated one methyl radical into formic ether, and a -OH linked with a
monosaccharide, a disaccharide or a trisaccharide unit by glycosidic linkage. It has the similar pharmacological activities,
anti-inflammatory, analgesic, antipyretic and antithrombotic as the previous salicylates’ without resulting in serious side
effects, particularly the gastrointestinal toxicity. Owing to the superiority of those significant bioactivities, methyl
salicylate glycosides have became a hot research area in NSAIDs for several years. This paper compiles all 9 naturally
occurring methyl salicylate glycosides, their distribution of the resource and pharmacological mechanism, which could
contribute to the new drug discovery
technique used for decades to obtain information about a substituent’s physicochemical property and biological activity.
There is step-by-step development in the concept of QSAR from 0D to 2D. These models suffer various limitations that
led to the development of 3D-QSAR. There are large numbers of literatures available on the utility of 3D-QSAR for drug
design. Three-dimensional properties of molecules with non-covalent interactions are served as important tool in the selection
of bioactive confirmation of compounds. With this view, 3D-QSAR has been explored with different advancements like
COMFA, COMSA, COMMA, etc. Some reports are also available highlighting the limitations of 3D-QSAR. In a way, to
overcome the limitations of 3D-QSAR, more advanced QSAR approaches like 4D, 5D and 6D-QSAR have been evolved.
Here, in this present review we have focused more on the present and future of more predictive models of QSAR studies.
The review highlights the basics of 3D to 6D-QSAR and mainly emphasizes the advantages of one dimension over the
other. It covers almost all recent reports of all these multidimensional QSAR approaches which are new paradigms in drug
discovery.
treatment of cancer. The main factor behind is cancer stem cells (CSCs) which are more resistant to conventional
chemotherapy, radiotherapy and are quite able to regenerate whole new tumor again if remain alive during treatment.
Targeting CSCs along with actively dividing cancer cells may significantly contribute to the solution of the problem of
resistance and relapse. Various approaches are implemented to eradicate CSCs which include CSC markers specific
compounds, Drugs which disturb niche and various inhibitors/modulators of signaling pathways. Hedgehog (Hh), Wnt
and Notch pathways are modulated/inhibited using various agents and shown beneficial results in multiple forms of
cancer. Many inhibitors/modulators of these pathways have been entered in the clinical trials. MicroRNAs have also been
developed as anti CSCs agents. In this review, we have covered current status of CSC targeting therapy based on CSC
markers, CSC niche, Hedgehog, Wnt, Notch pathway along with MicroRNA based targeting strategies and possibility of
implementation multi-targeted anti-CSC therapy for the better outcome of the results.
impact. The progress of AD is characterized by a severe loss in memory and cognition, leading to behavioral
changing, depression and death. During the last decades, only a few anticholinergic drugs were launched in the market,
mainly acetylcholinesterase inhibitors (AChEIs), with indications for the treatment of initial and moderate stages of AD.
The search for new AChEIs, capable to overcome the limitations observed for rivastigmine and tacrine, led Sugimoto and
co-workers to the discovery of donepezil. Besides its high potency, donepezil also exhibited high selectivity for AChE and
a very low toxicity. In this review, we discuss the main structural and pharmacological attributes that have made
donepezil the first choice medicine for AD, and a versatile structural model for the design of novel AChEIs, in spite of
multipotent and multitarget-directed ligands. Many recent data from literature transdue great efforts worldwide to produce
modifications in the donepezil structure that could result in new bioactive chemical entities with innovative structural
pattern. Furthermore, multi-potent ligands have also been designed by molecular hybridization, affording rivastigmine-,
tacrine- and huperzine-donepezil potent and selective AChEIs. In a more recent strategy, structural features of donepezil
have been used as a model to design multitarget-directed ligands, aiming at the discovery of new effective drug candidates
that could exhibit concomitant pharmacological activities as dual or multi- enzymatic inhibitors as genuine innovative
therapeutic alternatives for the treatment of AD.
number of anti-breast cancer agents isolated from CHM recently, showed very interesting structures, although some of the
mechanism of action is not quite clear. These unique chemical structures could be an important information resource for
new anti-breast cancer drugs’ design and discovery. This review summarizes these findings on anti-breast cancer agents
from CHM.
the presently available non-steroidal anti-inflammatory agents. The numbers of plant derived drugs have been screened for
their anti-inflammatory and anti-arthritic activity. Drug development in the recent times often relies on use of natural and
synthetic drugs, which are promising candidates as therapeutic agents for prevention of diseases and disorders. These
drugs possess different chemical structures, with wide range of therapeutic activities. The mechanism of Inflammation
mainly involve in development of serious diseases, such as cancer, rheumatoid arthritis, sprains, bronchitis, muscle pains,
chronic inflammatory bowel disease, persistent asthma, and liver fibrosis. Development of inflammatory events basically
related to various chemicals, such as glucocorticoids (GCs) and mometasone furoate (MF); endogenous factors such as
tumor necrosis factor alpha (TNF- ); enzymes and proteins such as copper and zinc-superoxide dismutase (SOD), proinflammatory
peptide substance (PPS), RGD peptides, interleukin-4 (IL-4), IL-10, interferon- (IFN- ), COX, LOX,
cytokines such as interleukin-1 (IL-1); reactive oxygen species (ROS), nitric oxide (NO) and prostaglandin E2; as well as
pro-inflammatory cells such as T and NK cells are well known to have an important role. Based on these correlations,
numerous assays were used for inflammatory mechanism research, which was described in this paper.
treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been
described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last
decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial
and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and
advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.
strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of
nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing
hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic
moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are
employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral
bioavailability, the mechanism of each additive.
various neurotransmitters in brain. They have been implicated in diverse potential therapeutic applications such as sleepwake
disorders, attention-deficient hyperactivity disorder, epilepsy, cognitive impairment and obesity. This review is an
attempt to elucidate the function of H3 receptors and their role in various CNS disorders. Also, it is aimed at collating the
information on efforts of various medicinal chemists to synthesize the H3 receptor agonists and antagonists in single
article.
role in the neuroendocrine system, due to its dense localization in various areas in the brain, its functions as a
neuromodulator have also been thoroughly investigated. Increasing evidence suggests that SST plays a crucial role in
memory and cognition. Synthetic forms, biologically active peptide sequences, SST receptor agonists and SST depleting
agents have been applied in animal models and in human studies of a number of neuropsychiatric disorders. The
translation of experimental data into clinical use could provide novel therapies in neurodegenerative disorders involving
cognitive dysfunctions. However in view of the controversial data reported concerning the different roles of the SST
receptor subtypes, and the lack of SST analogs that are able to cross diffusion barriers and act selectively at these receptor
subtypes, broader clinical use of SST analogs as cognitive enhancers is limited. This review covers the whole range of
available experimental results relating to the behavioral effects of SST, and highlights the potential for further
investigations