Antimicrobial, anticoagulant, and cytotoxic evaluation of multidrug resistance of new 1, 4-dihydropyridine derivatives

Abstract EN

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, 1 H NMR, 13C NMR, and mass spectra.

The synthesized compounds were screened for both antimicrobial and anticoagulant activities.

Compound 2e (MIC: 0.25 lg/mL) was highly active against Escherichia coli and compound 2c (MIC: 0.5 lg/mL) was also highly active against Pseudomonas aeruginosa compared with ciprofloxacin.

(MIC: 1 lg/mL) The antifungal activity of 2c (MIC: 0.5 lg/mL) against Candida albicans was high relative to that of clotrimazole (MIC: 1 lg/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-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 (GI50 = 0.02 lm) against HeLa cell line and 2e (GI50 = 0.03 lm) 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