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An efficient methodf or the oxidative cross-coupling of methylhetarenes with imidazoheterocycles by employing an eco-friendly iodine/DMSO reagent system has been developed.T his C(sp 2 )ÀHc arbonylation reactionp roceeds througha ni ns itu oxidation of am ethylhetarene into af ormylhetarene followed by an oxidative cross-coupling reaction with an imidazoheterocycle. This method has aw ide substrates cope and good functional group tolerance and enablest he constructiono falarge number of carbonylated imidazoheterocycles in very good yields.Scheme2.Oxidative couplings of 4-methylpyridine,b enzo[d]imidazo[2,1b]thiazole 9,a nd imidazopyridine 11. Scheme4.Putative reaction mechanism.Scheme3.Controle xperiments.

A series of 5-nitrofuran-triazole congeners were designed and synthesized by carrying out suitable structural modifications of the previously reported counterparts and were evaluated for their antimicrobial potential against both Gram-positive and Gram-negative bacterial strains. The compounds exhibited promising inhibition towards different Gram-positive pathogenic strains, while mild inhibitory effects were observed towards Gram-negative bacterial strains. Some of the compounds 9f, 9g, 9l and 9m were most active among the series, exhibiting a MIC value of 1.9 μg mL(-1) against different bacterial strains. The bactericidal activity was found to be in coherence with the bacterial growth inhibition data. The compounds were tested against fourteen different fungal strains and were found to possess excellent antifungal activities. Interestingly, all the compounds were equipotent to miconazole against one or more of the tested fungal strains and showed good activity against the other counterparts. A similar trend was observed in the case of their minimum fungicidal concentration values. Moreover, compound 9f exhibited two fold superior antifungal activity (MIC = 3.9 μg mL(-1)) than the standard miconazole (MIC = 7.8 μg mL(-1)) against C. albicans and C. parapsilosis. These compounds also effectively inhibited biofilm formation and compound 9f exhibited excellent anti-biofilm activity demonstrating a biofilm inhibitory concentration (BIC) as low as 0.8 μg mL(-1). A brief mechanistic study carried out on the most effective conjugate 9f indicated that it inhibits the ergosterol biosynthesis, thereby exhibiting antifungal effects. Molecular modelling studies carried out to study the binding modes of 9f correlates well with the antifungal activity and supported by ergosterol biosynthesis inhibition assay data. Most of these compounds exhibited ten times lower cytotoxicity toward the normal cells compared to the antimicrobial activity.

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