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, 1H NMR, 13C NMR, and mass spectra. The synthesized compounds were screened for both antimicrobial and anticoagulant activities. Compound 2e (MIC: 0.25 μg/mL) was highly active against Escherichia coli and compound 2c (MIC: 0.5 μg/mL) was also highly active against Pseudomonas aeruginosa compared with ciprofloxacin. (MIC: 1 μg/mL) The antifungal activity of 2c (MIC: 0.5 μg/mL) against Candida albicans was high relative to that of clotrimazole (MIC: 1 μg/mL). Anticoagulant activity was determined by activated partial thromboplastin time (APTT) and prothrombin time (PT) coagulation assays. Compound 4-(4-hydroxyphenyl)-2,6-dimethyl-N3,N5-bis(5-phenyl-1,3,4-thiadiazol-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 (GI50 = 0.02 μm) against HeLa cell line and 2e (GI50 = 0.03 μm) 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.
Keywords: 1,4-Dihydropyridine derivatives; Anticoagulant activity; Antimicrobial activity; Structure activity relationship; Ultrasound irradiation.