Formazan analogous: Synthesis, antimicrobial activity, dihydrofolate reductase inhibitors and docking study

Abstract

In this article, we synthesized new formazan derivatives and they were evaluated for their antimicrobial activity and their minimum inhibitory concentration values against three gram-negative and three gram-positive bacterial strains and three fungal species. The structure of all formed formazan derivatives was established based on their spectral data. All formazan analogous revealed promising antimicrobial activity with MIC value range of 1.95 – 62.5 μg/mL. Compounds 3c and 5a showed good results against the MRSA strain (MIC 3.91 μg/mL). Furthermore, compounds 3c, 5a,b, 7a,b and 9 exhibited potent dihydrofolate reductase inhibition IC50 rang value 0.142 – 4.033 µM, especially compound 3c that showed higher DHFR inhibitory activity (IC50= 0.142µM) than trimethoprim (IC50= 0.188 µM). Compounds 3c, 5a, 7a and 9 displayed comparable 14α-demethylase inhibition (IC50= 4.79 – 19.50 µM) to that of fluconazole (IC50= 2.81µM). Molecular docking studies revealed that all formazan analogous have good binding mode and an affinity to DHFR and 14α-demethylase binding site. Finally, metabolic pathways and anticipated metabolites of compounds 3c and 5a were predicted.