Synthesis of Some 1,4,6-Trisubstituted-2-oxo-1,2-dihydropyridine-3-carbonitriles and Their Biological Evaluation as Cytotoxic and Antimicrobial Agents

A series of novel 1,4,6‐trisubstituted‐2‐oxo‐1,2‐dihydropyridine‐3‐carbonitriles supported with some functionalities reported to contribute to significant chemotherapeutic potential were synthesized and evaluated for their antimicrobial and/or cytotoxic activities. Thirteen compounds exhibited cytotoxic potential against a panel of three human tumor cell lines. Compounds 15, 23, and 24 proved to be the most active agents with a broad spectrum of cytotoxic activity. Analog 24 was considered as the most active cytotoxic agent, being 2.5 times more active than doxorubicin against the colon HT29 carcinoma cell line. Seventeen compounds were able to exert a variable antimicrobial profile, among which analogs 15, 20, 21, 23, and 24 were prominently active. The highest antimicrobial potential was displayed by analog 24, being equipotent to ampicillin against Staphylococcus aureus and Escherichia coli, together with a considerable antifungal activity comparable with clotrimazole. Collectively, compounds 15, 23, and 24 could be considered as possible dual antimicrobial‐anticancer candidates. Novel substituted 2‐oxo‐1,2‐dihydropyridine‐3‐carbonitriles (A, B) and some derived 1,2,4‐triazolo[4,3‐a]‐pyridinones (C) were synthesized and evaluated for their antimicrobial and cytotoxic activities. Three analogs are possible dual antimicrobial‐anticancer candidates. 4‐(Benzo[1,3]dioxol‐5‐yl)‐3‐cyano‐6‐(4‐methoxyphenyl)‐2‐oxo‐N‐phenylpyridine‐1(2H)‐carbothioamide 24 is more effective than doxorubicin against HT29 cells.