International Journal of Molecular Sciences, Dec 25, 2023
Thiazolidin-4-ones have a broad range of medical and clinical implementation, which is important ... more Thiazolidin-4-ones have a broad range of medical and clinical implementation, which is important for pharmaceutical and medicinal chemistry. This heterocyclic core has been reported to possess a diversity of bioactivities, including antimicrobial and antibiofilm-forming potential. The resistance of biofilms to antibiotics or disinfectants is a serious medical problem. Therefore, there is a natural need to discover new effective structures with properties that inhibit biofilm formation. This review aims to analyze the antibiofilm features of thiazolidin-4-ones described in the literature over the last two decades. The information gathered in this review could benefit the rational design of new effective antibiofilm small molecules with thiazolidin-4-one cores.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ABSTRACT The compounds (III) and (IV) are screened for their antimicrobial activity against Gram-... more ABSTRACT The compounds (III) and (IV) are screened for their antimicrobial activity against Gram-positive and Gram-negative bacteria.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gond... more Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gondii (Tg), cause major public health problems worldwide. In addition, serious and challenging health problems of co-infections of Tg with Mtb have been recorded, especially in developing countries. Due to this fact, as well as the frequent cases of resistance to the current drugs, novel anti-infectious therapeutics, especially those with dual (anti-Tg and anti-Mtb) modes of action, are needed. To address this issue, we explored the anti-Tg potential of thiazolidinedione-based (TZD-based) hybrid molecules with proven anti-Mtb potency. Several TZD hybrids with pyridine-4-carbohydrazone (PCH) or thiosemicarbazone (TSC) structural scaffolds were more effective and more selective than sulfadiazine (SDZ) and trimethoprim (TRI). Furthermore, all of these molecules were more selective than pyrimethamine (PYR). Further studies for the most potent TZD-TSC hybrids 7, 8 and 10 and TZD-PCH hybrid molec...
The rhodanine core is a well-known privileged heterocycle in medicinal chemistry. The rhodanines,... more The rhodanine core is a well-known privileged heterocycle in medicinal chemistry. The rhodanines, as subtypes of thiazolidin-4-ones, show a broad spectrum of biological activity, including anticancer properties. This review aims to analyze the anticancer features of the rhodanines described over the last decade in the scientific literature. The structure–activity relationship of rhodanine derivatives, as well as some of the molecular targets, were discussed. The information contained in this review could be of benefit to the design of new, effective small molecules with anticancer potential among rhodanine derivatives or their related heterocycles.
In our present research, we synthesised new thiazolidine-2,4-diones (<b>12–28</b>). A... more In our present research, we synthesised new thiazolidine-2,4-diones (<b>12–28</b>). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC<sub>50</sub> values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound <b>18</b> revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative <b>18</b> showed meaningfully lower IC<sub>50</sub> values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition <i>in vitro.</i> According to our screening resul...
Journal of Labelled Compounds and Radiopharmaceuticals, 2011
Since none of the available methods was suitable for the synthesis of isotopically labelled oxama... more Since none of the available methods was suitable for the synthesis of isotopically labelled oxamate, a new procedure has been developed in our laboratory, based on the known procedures, but with substantial modifications. The method is convenient and gives reproducibly 17% yield based on KCN used. The strategy is considered suitable for labelling oxamate with 15 N and 13 C or 14 C when starting with labelled KCN and can be easily modified for the synthesis of 18 O-carbonyllabelled oxamate.
The new methyl [3-(4-chlorophenyl)-2-{[(2,4-dichloro-1,3-thiazol-5-yl)methylidene]hydrazinylidene... more The new methyl [3-(4-chlorophenyl)-2-{[(2,4-dichloro-1,3-thiazol-5-yl)methylidene]hydrazinylidene}-4-oxo-1,3-thiazolidin-5-ylidene]acetate was synthesized from 4-(4-chlorophenyl)-1-(2,4-dichloro-1,3-thiazol-5-yl)methylidene-3-thiosemicarbazide using dimethyl acetylenedicarboxylate as thia-Michael reaction acceptor. New compounds (3 and 4) were characterized by IR, 1H and 13C NMR spectroscopy methods.
The two series of thiosemicarbazone derivatives with thiazolidine-2,4-dione (TZD) core were desig... more The two series of thiosemicarbazone derivatives with thiazolidine-2,4-dione (TZD) core were designed and synthesized. The antimycobacterial activity of the target compounds was tested against Mycobacterium tuberculosis H37Ra by broth microdilution method with resazurin as an indicator of the metabolic activity of mycobacteria. Conducted studies revealed antimycobacterial activity in the concentration range of 0.031-64 µg/ml for 31 synthesized derivatives with TZD core. The highest antimycobacterial activity (MIC = 0.031-0.125 µg/ml) was demonstrated for the new group of compounds: TZD-based hybrids with 4-unsubstituted thiosemicarbazone substituent. Furthermore, all the tested compounds within this group were characterized by low cytotoxicity. Among tested compounds, two compounds are the most promising potential antimycobacterial agents since they not only show very low MIC values, but also non-toxicity against Vero cells at tested concentration range. High effectiveness and safety...
In the reaction of (2,4-dioxothiazolidin-5-yl)acetyl chloride with 1,2,4-triazole, 4-phenyl-1,2,4... more In the reaction of (2,4-dioxothiazolidin-5-yl)acetyl chloride with 1,2,4-triazole, 4-phenyl-1,2,4-triazolin-5-one and 4-phenyl-1,2,4-triazolin-5-thione, the new corresponding amides (2-4) were obtained. For compounds 2 and 4 effects on central nervous system (CNS) of mice were studied.
By the reaction of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetyl chlorides with 4-phenylthiosemic... more By the reaction of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetyl chlorides with 4-phenylthiosemicarbazide, acylthiosemicarbazide derivatives 4-6 were obtained. The cyclization of 4-6 in acid medium led to 1,3,4-thiadiazole derivatives 7-9. The structure of the compounds was confirmed by elemental analysis and IR, H NMR, 13C NMR and MS spectra. The effects of compounds 7 and 9 on the central nervous system (CNS) of mice were studied.
In the reaction of 5-arylidene-2,4-dioxothiazolidine-3-acetic acid chloride with 1,2,4-triazole, ... more In the reaction of 5-arylidene-2,4-dioxothiazolidine-3-acetic acid chloride with 1,2,4-triazole, 1,2,4-triazoline-5-one and 1,2,4-triazoline-5-thione, the new corresponding 5-arylidene-2,4-dioxothiazolidine-3-acetic acid amides (5-16) were obtained. Compounds 6, 14 i 15 were investigated in vitro for their antioxidant activity.
Thiazolidin-4-ones is an important heterocyclic ring system of a pharmacophore and a privileged s... more Thiazolidin-4-ones is an important heterocyclic ring system of a pharmacophore and a privileged scaffold in medicinal chemistry. This review is focused on the latest scientific reports regarding biological activities of thiazolidin-4-ones published in 2020 and 2021. The review covers recent information about antioxidant, anticancer, anti-inflammatory, analgesic, anticonvulsant, antidiabetic, antiparasitic, antimicrobial, antitubercular and antiviral properties of thiazolidin-4-ones. Additionally, the influence of different substituents in molecules on their biological activity was discussed in this paper. Thus, this study may help to optimize the structure of thiazolidin-4-one derivatives as more efficient drug agents. Presented information may be used as a practical hint for rational design of new small molecules with biological activity, especially among thiazolidin-4-ones.
The development of drug-resistant bacteria is currently one of the major challenges in medicine. ... more The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31...
International Journal of Molecular Sciences, Dec 25, 2023
Thiazolidin-4-ones have a broad range of medical and clinical implementation, which is important ... more Thiazolidin-4-ones have a broad range of medical and clinical implementation, which is important for pharmaceutical and medicinal chemistry. This heterocyclic core has been reported to possess a diversity of bioactivities, including antimicrobial and antibiofilm-forming potential. The resistance of biofilms to antibiotics or disinfectants is a serious medical problem. Therefore, there is a natural need to discover new effective structures with properties that inhibit biofilm formation. This review aims to analyze the antibiofilm features of thiazolidin-4-ones described in the literature over the last two decades. The information gathered in this review could benefit the rational design of new effective antibiofilm small molecules with thiazolidin-4-one cores.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ABSTRACT The compounds (III) and (IV) are screened for their antimicrobial activity against Gram-... more ABSTRACT The compounds (III) and (IV) are screened for their antimicrobial activity against Gram-positive and Gram-negative bacteria.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gond... more Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gondii (Tg), cause major public health problems worldwide. In addition, serious and challenging health problems of co-infections of Tg with Mtb have been recorded, especially in developing countries. Due to this fact, as well as the frequent cases of resistance to the current drugs, novel anti-infectious therapeutics, especially those with dual (anti-Tg and anti-Mtb) modes of action, are needed. To address this issue, we explored the anti-Tg potential of thiazolidinedione-based (TZD-based) hybrid molecules with proven anti-Mtb potency. Several TZD hybrids with pyridine-4-carbohydrazone (PCH) or thiosemicarbazone (TSC) structural scaffolds were more effective and more selective than sulfadiazine (SDZ) and trimethoprim (TRI). Furthermore, all of these molecules were more selective than pyrimethamine (PYR). Further studies for the most potent TZD-TSC hybrids 7, 8 and 10 and TZD-PCH hybrid molec...
The rhodanine core is a well-known privileged heterocycle in medicinal chemistry. The rhodanines,... more The rhodanine core is a well-known privileged heterocycle in medicinal chemistry. The rhodanines, as subtypes of thiazolidin-4-ones, show a broad spectrum of biological activity, including anticancer properties. This review aims to analyze the anticancer features of the rhodanines described over the last decade in the scientific literature. The structure–activity relationship of rhodanine derivatives, as well as some of the molecular targets, were discussed. The information contained in this review could be of benefit to the design of new, effective small molecules with anticancer potential among rhodanine derivatives or their related heterocycles.
In our present research, we synthesised new thiazolidine-2,4-diones (<b>12–28</b>). A... more In our present research, we synthesised new thiazolidine-2,4-diones (<b>12–28</b>). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC<sub>50</sub> values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound <b>18</b> revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative <b>18</b> showed meaningfully lower IC<sub>50</sub> values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition <i>in vitro.</i> According to our screening resul...
Journal of Labelled Compounds and Radiopharmaceuticals, 2011
Since none of the available methods was suitable for the synthesis of isotopically labelled oxama... more Since none of the available methods was suitable for the synthesis of isotopically labelled oxamate, a new procedure has been developed in our laboratory, based on the known procedures, but with substantial modifications. The method is convenient and gives reproducibly 17% yield based on KCN used. The strategy is considered suitable for labelling oxamate with 15 N and 13 C or 14 C when starting with labelled KCN and can be easily modified for the synthesis of 18 O-carbonyllabelled oxamate.
The new methyl [3-(4-chlorophenyl)-2-{[(2,4-dichloro-1,3-thiazol-5-yl)methylidene]hydrazinylidene... more The new methyl [3-(4-chlorophenyl)-2-{[(2,4-dichloro-1,3-thiazol-5-yl)methylidene]hydrazinylidene}-4-oxo-1,3-thiazolidin-5-ylidene]acetate was synthesized from 4-(4-chlorophenyl)-1-(2,4-dichloro-1,3-thiazol-5-yl)methylidene-3-thiosemicarbazide using dimethyl acetylenedicarboxylate as thia-Michael reaction acceptor. New compounds (3 and 4) were characterized by IR, 1H and 13C NMR spectroscopy methods.
The two series of thiosemicarbazone derivatives with thiazolidine-2,4-dione (TZD) core were desig... more The two series of thiosemicarbazone derivatives with thiazolidine-2,4-dione (TZD) core were designed and synthesized. The antimycobacterial activity of the target compounds was tested against Mycobacterium tuberculosis H37Ra by broth microdilution method with resazurin as an indicator of the metabolic activity of mycobacteria. Conducted studies revealed antimycobacterial activity in the concentration range of 0.031-64 µg/ml for 31 synthesized derivatives with TZD core. The highest antimycobacterial activity (MIC = 0.031-0.125 µg/ml) was demonstrated for the new group of compounds: TZD-based hybrids with 4-unsubstituted thiosemicarbazone substituent. Furthermore, all the tested compounds within this group were characterized by low cytotoxicity. Among tested compounds, two compounds are the most promising potential antimycobacterial agents since they not only show very low MIC values, but also non-toxicity against Vero cells at tested concentration range. High effectiveness and safety...
In the reaction of (2,4-dioxothiazolidin-5-yl)acetyl chloride with 1,2,4-triazole, 4-phenyl-1,2,4... more In the reaction of (2,4-dioxothiazolidin-5-yl)acetyl chloride with 1,2,4-triazole, 4-phenyl-1,2,4-triazolin-5-one and 4-phenyl-1,2,4-triazolin-5-thione, the new corresponding amides (2-4) were obtained. For compounds 2 and 4 effects on central nervous system (CNS) of mice were studied.
By the reaction of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetyl chlorides with 4-phenylthiosemic... more By the reaction of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetyl chlorides with 4-phenylthiosemicarbazide, acylthiosemicarbazide derivatives 4-6 were obtained. The cyclization of 4-6 in acid medium led to 1,3,4-thiadiazole derivatives 7-9. The structure of the compounds was confirmed by elemental analysis and IR, H NMR, 13C NMR and MS spectra. The effects of compounds 7 and 9 on the central nervous system (CNS) of mice were studied.
In the reaction of 5-arylidene-2,4-dioxothiazolidine-3-acetic acid chloride with 1,2,4-triazole, ... more In the reaction of 5-arylidene-2,4-dioxothiazolidine-3-acetic acid chloride with 1,2,4-triazole, 1,2,4-triazoline-5-one and 1,2,4-triazoline-5-thione, the new corresponding 5-arylidene-2,4-dioxothiazolidine-3-acetic acid amides (5-16) were obtained. Compounds 6, 14 i 15 were investigated in vitro for their antioxidant activity.
Thiazolidin-4-ones is an important heterocyclic ring system of a pharmacophore and a privileged s... more Thiazolidin-4-ones is an important heterocyclic ring system of a pharmacophore and a privileged scaffold in medicinal chemistry. This review is focused on the latest scientific reports regarding biological activities of thiazolidin-4-ones published in 2020 and 2021. The review covers recent information about antioxidant, anticancer, anti-inflammatory, analgesic, anticonvulsant, antidiabetic, antiparasitic, antimicrobial, antitubercular and antiviral properties of thiazolidin-4-ones. Additionally, the influence of different substituents in molecules on their biological activity was discussed in this paper. Thus, this study may help to optimize the structure of thiazolidin-4-one derivatives as more efficient drug agents. Presented information may be used as a practical hint for rational design of new small molecules with biological activity, especially among thiazolidin-4-ones.
The development of drug-resistant bacteria is currently one of the major challenges in medicine. ... more The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31...
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