An Expeditious Approach to the Synthesis of Novel Quinolino and Diazacino Condensed Analogues of Azepino [3, 2-b] Carbazole-2-one of Medicinal Interest

Abstract:

Background: Quinolino and diazacino are important heterocyclics moiety, which have been reported to possess various activities such as antiallergenic, antifungal, hypocholesterolemic, antibacterial and antiviral activities. The activities of these compounds were related to inhibition of bacterial dehydrogenase enzyme which is one of the important targets studied for designing of antimicrobial drugs. Further, molecular docking approached is used in the present study for confirming potent molecules. Objectives: Aim of the study is to synthesize a series of quinolino and diazacino condensed analogues and evaluation of their anti-microbial activity. Methods: Quinolino and diazacino condensed analogues of azepino [3, 2-b] carbazole-2-one were synthesized by Friedel-Craft acylation and Pfitzinger reaction. Structures of synthesized compounds were characterized by FTIR and HNMR and were evaluated for antimicrobial activity by in-vitro bacterial dehydrogenase activity agar well diffusion assay. Further, in order to determine the binding affinity, molecular docking of synthesized compounds was also performed using bacterial (3NUH of E. coli) and fungal proteins (1FI4). In addition, bacterial dehydrogenase inhibitory activity of most active compound was performed using MTT assay. Results: Synthesized compounds (3, 4 and 6) caused impressive antibacterial and antifungal activities in-vitro assay when compared to the ciprofloxacin and fluconazole. And molecular docking studies also revealed that the synthesized compounds 3, 4 and 6 exhibits good to excellent affinity towards target microbial proteins. Conclusion: Synthesized compounds (3, 4 and 6) hold substantial antibacterial potential and require further exploration to establish them as therapeutic candidates in clinical management.

Key words: Antimicrobial, Azepino [3, 2-b] carbazole-2-one, Pfitzinger reaction, Beckmann rearrangement, Organocatalyst.