New benzothiazole and benzoxazole picolinamide conjugates as potential anti-cancer agents: Design, synthesis, molecular docking and anticancer studies
•An efficient synthesis was developed for the synthesis of N-(benzo[d]thiazol/oxazole-2-yl)−6-methyl-5-phenylpicolinamide derivatives.•Their anticancer potential was evaluated against DU-145(prostrate) and SKOV-3 (ovarian) cell lines.•The presence of electron rich OCH3 group on phenyl ring and thiaz...
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Published in | Journal of molecular structure Vol. 1309; p. 138153 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Elsevier B.V
05.08.2024
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Subjects | |
Online Access | Get full text |
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Summary: | •An efficient synthesis was developed for the synthesis of N-(benzo[d]thiazol/oxazole-2-yl)−6-methyl-5-phenylpicolinamide derivatives.•Their anticancer potential was evaluated against DU-145(prostrate) and SKOV-3 (ovarian) cell lines.•The presence of electron rich OCH3 group on phenyl ring and thiazole ring in the structure of compound 5f makes it to show to strong cytotoxicity.•The molecular binding studies showed that compounds 5f and 5e had strong binding to human EGFR with binding energies of −8.5 and −8.2 Kcal/mol.
An efficient synthesis was developed for the synthesis of N-(benzo[d]thiazol/oxazole-2-yl)-6-methyl-5-phenylpicolinamide derivatives(5a-5 h;8 compounds) with good yields by condensation reactions using benzo[d]thiazol/oxazole-2-amines with 5‑bromo-6‑methoxy picolinic acids in the presence of Hexafluorophosphate Azabenzotriazole Tetramethyl Uronium (HATU)/ 4-Dimethylaminopyridine (DMAP) in Dimethylformamide (DMF) followed by coupling with phenylboronic acid in the presence of 1,1 -Bis(diphenylphosphino)ferrocene dichloropalladium(II):(Pd(dppf)Cl2·CH2Cl2), Cs2CO3 in Dioxane/H2O medium. Further, the anticancer potential of these derivatives was evaluated against DU-145(prostrate) and SKOV-3 (ovarian) cell lines. Results indicated moderate to good activity, with compound 5f exhibiting the best cytotoxicity with IC50 values of 8.3 and 8.9 µM for SKOV-3 and DU145 cells respectively as compared to standard Doxorubicin values 0.53 ± 0.08 and 0.68 ± 0.05 for same cell lines.. Additionally, molecular binding studies showed that compounds 5f and 5e had strong binding to human epidermal growth factor receptor, with binding energies of -8.5 and -8.2 Kcal/mol indicates conformational change in the structure of the receptor, leading to activation of signaling pathways promoting proliferation. So, the presence of electron rich OCH3 group on phenyl ring as well as thiazole ring in the designed molecule 5f makes it more potent to show strong cytotoxicity which was also revealed by its binding studies towards the human epidermal growth factor receptor. However, fluorine makes the compounds 5 g and 5 h to show moderate activity against these cancer cell lines.
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ISSN: | 0022-2860 1872-8014 |
DOI: | 10.1016/j.molstruc.2024.138153 |