Abstract
A new series of 1,4-dihydropyridine derivatives (2a-h, 3a-e, and 4a-e) were systematically designed and synthesized via ultrasound irradiation methods with easy work-up and good yields. Compounds structures were confirmed by IR, H-1 NMR, C-13 NMR, and mass spectra. The synthesized compounds were screened for both antimicrobial and anticoagulant activities. Compound 2e (MIC: 0.25 mu g/mL) was highly active against Escherichia coli and compound 2c (MIC: 0.5 mu g/mL) was also highly active against Pseudomonas aeruginosa compared with ciprofloxacin. (MIC: 1 mu g/mL) The antifungal activity of 2c (MIC: 0.5 mu g/mL) against Candida albicans was high relative to that of clotrimazole (MIC: 1 mu g/mL). Anticoagulant activity was determined by activated partial thromboplastin time (APTT) and prothrombin time (PT) coagulation assays. Compound 4-(4-hydroxyphenyl)-2,6-dimethyl-N-3,N-5-bis(5-phenyl-1,3,4-t hiadiazol-2-yl)-1,4-dihydropyridine-3,5-dicarboxamide 3d (> 1000 s in APTT assays) was highly active in anticoagulant screening compared with the reference of heparin.
Cytotoxicity was evaluated using HepG2 (liver), HeLa (cervical), and MCF-7 (breast) cancer cell lines, with high toxicities observed for 2c (GI(50) = 0.02 mu m) against HeLa cell line and 2e (GI(50) = 0.03 mu m) equipotant against MCF-7 cell line. Therefore, the compounds 2e, 2c and 3d can serve as lead molecules for the development of new classes of antimicrobial and anticoagulant agent. (C) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.