In our endeavor towards the development of effective anticancer agents, a novel series of pyridin... more In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a-n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds 8e and 8n were found to be the most active congeners against MCF-7 cells (IC 50 = 0.22 and 1.88 µM after 48 h treatment; 0.11 and 0.80 µM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC 50 = 1.93 µM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l-n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for 8b; 12-78%, GI for 8e; 15-91%). Pyridines 8b and 8e were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC 50 values 5.0 ± 1.91 and 3.93 ± 0.73 µM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study.
A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-h was prepared conveniently from diacetyl pyrazol... more A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-h was prepared conveniently from diacetyl pyrazoles 2a,b. All reactions were carried out under conventional thermal heating and/or microwave irradiation. The structure of the latter functionally pyrazoles was confirmed under the bases of their IR, mass, 1 H NMR and 13 C NMR. The X-ray diffraction of compound 3e not only confirmed the chemical structure of 3a-h, but also showed the E configuration of their chalcone moieties. Treatment of compound 3e with phenyl hydrazine in presence of acetic acid afforded the tri-pyrazle 4. The anti-inflammatory activity of the newly synthesized compounds was investigated. Some of these compounds showed a moderate activity when compared with indomethacin as a reference drug. The combination between chalcone and pyrazole moieties revealed a variable effect in anti-inflammatory activity.
In our endeavor towards the development of effective anticancer agents, a novel series of pyridin... more In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a-n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds 8e and 8n were found to be the most active congeners against MCF-7 cells (IC 50 = 0.22 and 1.88 µM after 48 h treatment; 0.11 and 0.80 µM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC 50 = 1.93 µM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l-n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for 8b; 12-78%, GI for 8e; 15-91%). Pyridines 8b and 8e were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC 50 values 5.0 ± 1.91 and 3.93 ± 0.73 µM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study.
A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-h was prepared conveniently from diacetyl pyrazol... more A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-h was prepared conveniently from diacetyl pyrazoles 2a,b. All reactions were carried out under conventional thermal heating and/or microwave irradiation. The structure of the latter functionally pyrazoles was confirmed under the bases of their IR, mass, 1 H NMR and 13 C NMR. The X-ray diffraction of compound 3e not only confirmed the chemical structure of 3a-h, but also showed the E configuration of their chalcone moieties. Treatment of compound 3e with phenyl hydrazine in presence of acetic acid afforded the tri-pyrazle 4. The anti-inflammatory activity of the newly synthesized compounds was investigated. Some of these compounds showed a moderate activity when compared with indomethacin as a reference drug. The combination between chalcone and pyrazole moieties revealed a variable effect in anti-inflammatory activity.
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