Synthesis, Characterization and ADME Prediction Study of Heterocyclic Moieties-linked Indole Derivatives as Potential Antimicrobial Agents

Abstract

Background: Heterocyclic compounds are vital for research due to their diverse pharmacological profiles. They are key structural components of many of the potent antimicrobial drugs available on the market today but still facing the problem of drug resistance by microbes. Indole and its derivatives display versatile pharmacological activities, such as analgesic, antimicrobial, antidepressant, antidiabetic, anti-convulsant, antihelmintic, and anti-inflammatory. Objective: Indole ring was linked to other key heterocyclic moieties, such as morpholine, imidazole, piperidine, and piperazine at the active 3rd position by Schotten-Baumann reaction, and further evaluated against Gram-positive and Gram-negative bacteria with the hope to develop potent antimicrobial agents. Method: Synthesis of derivatives was performed under appropriate conditions and characterized by IR, NMR (1H and 13C), and CHN elemental analysis. Further, in vitro assays were used to evaluate their antimicrobial activity by agar diffusion and agar streak dilution method against Bacillus subtilis (ATCC 6633) and Escherichia coli (ATCC 25922). ADME properties were also calculated using the Swiss ADME online program. Results: Compounds 4b, 4f, 4i, 4k showed maximum potency in both in vitro assays calculated as the zone of inhibition (17±0.5 mm-22±0.25 mm) and minimum inhibitory concentration (MIC= 6.25-25 μg/ml)) comparable to standard drugs ciprofloxacin and ampicillin. ADME results showed zero violation of the Lipinski’s rule. Conclusion: A great deal of work has been done on the synthesis and evaluation of indole derivatives to explore their antimicrobial effect. These findings may lead to the design and development of more effective antimicrobial drug candidates.