Synthesis and biological evaluation of compounds which contain pyrazole,thiazole and naphthalene ring as antitumor agents |
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| Affiliation: | 1. Department of Chemistry, Al.I. Cuza University of Iasi, 11 Carol I, 700506 Iasi, Romania;2. Department of Biology, Al.I. Cuza University of Iasi, 11 Carol I, 700506 Iasi, Romania;1. Pharmaceutical Sciences Research Center, Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;2. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;3. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran;4. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;1. Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt, 12311 Cairo, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt;3. Department of Pharmacology and Biochemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt, 12311 Cairo, Egypt;4. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt |
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| Abstract: | A series of compounds which contain pyrazole, thiazole and naphthalene ring (1a–7a, 1b–7b, 1c–7c, 1d–7d) were firstly synthesized and their anti-proliferative activity, EGFR inhibitory activity, cytotoxicity and inhibition to Hela cell migration were evaluated. Compound 2-(3-(3,4-dimethylphenyl)-5-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (7d) displayed the most potent inhibitory activity (IC50 = 0.86 μM for Hela and IC50 = 0.12 μM for EGFR). Structure–activity relationship (SAR) analysis showed that the anti-proliferative activity was affected by A-ring-substituent (–OCH3 > –CH3 > –H > –Br > –Cl > –F). Docking simulation of compound 7d into EGFR active site showed that naphthalene ring of 7d with LYS721 formed two p–π bonds, which enhanced antitumor activity. Therefore, compound 7d may be developed as a potential antitumor agent. |
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| Keywords: | EGFR inhibitors Anti-tumor activity Cell migration Structure–activity relationship |
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