Synthesis, Characterization and in Silico Pharmacological Predictions Studies of Some Oxadiazole, Triazole, Pyrrole Based Fused Indole Derivatives as Potential Antimicrobial Agents

Author(s): Ramesh S. Gani*, Avinash Kundadka Kudva, Vinothkannan Ravichandiran, Dhananjaya B. L, Ravindra B. Chougale and Karabasana Gouda T

Abstract: Indole moiety is one of the key heterocyclic rings presents in a large number of biological active molecules. Synthesis of 5-hydroxy derivatives has attracted considerable attention in view of therapeutic applications. In the present study, a series of 1-phenylethyl-2-methyl-3-ethoxycarbonyl-5-hydroxyindole derivatives have been synthesized. All the synthesized compounds have been characterized by using FT-IR, 1H NMR, 13CNMR spectroscopy and further supported by mass spectroscopy. All the synthesized compounds were screened for their antibacterial and antifungal activity by using well diffusion assays. Molecular docking investigations with Glucosamine 6-phosphate synthase (G6P), revealed lower binding energy values for lead compound (1-phenylethyl-2-methyl-3-ethoxycarbonyl-5-hydroxyindole) amongst all derivatives and Ciprofloxacin, indicating most favourable hydrogen-bond interactions with active site residues of G6P. The lead was able to interact with most active site residues Cys1, Trp74, Gly99 of G6P suggesting their strong inhibitory potential similar to Ciprofloxacin. Along with hydrogen bonds, the lead was able to make a π-π stacking with Arg26 of G6P that makes this interaction different than Ciprofloxacin. The lead molecule and its derivatives showed promising antimicrobial activities comparable to standard drugs. Also, in silico analysis revealed that these compounds followed Lipinski’s rule of five and showed no signs of carcinogenicity and lower risk of toxicity. Hence it may be developed as a potential pharmacological agent.

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