Insights into Antimicrobial Potential of Styrylquinoline Derivatives

A total of 64 ring-substituted 2-styrylquinolines were designed and tested against a battery of microbial pathogens: Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, clinical isolates of methicillin-resistant S. aureus (MRSA), Mycobacteium tuberculosis H37Ra/ATCC 25177, Mycobacterium smegmatis ATCC 700084, Mycobacterium kansasii DSM 44162, Candida albicans CCM 8361, Candida krusei CCM 8271 and Candida parapsilosis CCM 8260. In addition, all compounds were investigated for their anticancer potential on colon cancer cell lines HCT 116 p53+/+ and HCT 116 p53-/- as well as the effect against normal human dermal fibroblasts (NHDF). Twenty derivatives showed remarkable antimicrobial activity comparable to or better than clinically used drugs (ampicillin, ciprofloxacin, rifampicin, amphotericin B). The most effective compounds were substituted on styryl with 2,6-Cl, 2-NO ₂ , 2,4-NO ₂ , 4-CN, 2-OAc-5-Cl and 2-OH-5-NO ₂ . Chlorination of the quinoline at the 5- and 7-position and the free hydroxylic group at the 8-position of the quinoline resulted in increased and broadened efficacy. All the antimicrobial active derivatives did not show significant effect on normal human dermal fibroblasts, except for 2,6-Cl-styryl derivatives. The antimycobacterial active compounds were able to inhibit cellular respiration in all tested mycobacterial species. ( E )-5,7-dichloro-2-[2-(2-nitrophenyl)vinyl]-quinolin-8-ol ( D4 ) and ( E )-5,7-dichloro-2-[2-(2,4-dinitrophenyl)vinyl]-quinolin-8-ol ( D10 ) were the most antimicrobial effective agents simultaneously with high anticancer activity and negligible cytotoxicity against normal human cells. Thus, promising active agents with dual, anti-infectious, and anticancer effects, were identified.