Synthesis and Molecular Modelling Studies of Coumarin and 1‐Aza‐Coumarin Linked Miconazole Analogues and Their Antimicrobial Properties

• Published in: ChemistrySelect (Weinheim) 2020-01, Vol.5 (4), p.1322-1330
• Main Authors: Sutar, Suraj M., Savanur, Hemantkumar M., Malunavar, Shruti S., Pawashe, Geeta M., Aridoss, Gopalakrishnan, Kim, Kang Min, Lee, Jin Young, Kalkhambkar, Rajesh G.
• Format: Article
• Language: English
• Subjects: 1-Aza-Coumarin; Antimicrobial Activity; Coumarin; Miconazole; Molecular Modelling Studies
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201903572

A series of coumarin and 1‐Aza coumarin analogues of miconazole(5 a‐6 e) were synthesized from 2‐bromo‐1‐(2,4‐dichlorophenyl)ethanone and diversification was achieved by synthesizing coumarin‐benzimidazole(7 a‐7 e) and 1‐aza coumarin‐benzimidazole(8 a‐8 e) hybrids of miconazole and evaluated for in‐vitro anti‐microbial activities. Among the tested compounds, 8 b‐8 e were found to be effective as anti‐fungal against C. albicans, C. utilis and C. krusei, with activity compared to that of the standard. Comparative docking studies with mevalonate‐5‐diphosphatedecarboxylase shows better binding affinity than imidazole counterparts which is primarily attributed to extended π‐alkyl interactions facilitated by benzimidazole. A series of coumarin, 1‐Azacoumarin, Imidazole and benzimidazole linked miconazole analogue of compounds were synthesized by modification in the readily available miconazole moiety to screen it towards its antimicrobial properties. Molecular modelling studies found to be effective with excellent binding affinity results. Further, some of the synthesized compounds exhibited excellent antibacterial and antifungal activity compared to that of standard. Further.