Carbazole Tethered Triazoles as Potential NS5A/NS5B Inhibitors: Synthesis, Molecular Docking, MD Simulation, ADMET and DFT Studies

ABSTRACT Owing to the strong antiviral potential of carbazole derivatives, in this study a novel synthesis of aryl‐substituted triazole derivatives 11 ( a – g ) and improved synthesis, in terms of increased yields and reduced reaction times, of carbazole‐based benzofuran‐substituted triazole derivatives 9 ( a – j ) have been carried out via a conventional and cetyl trimethyl ammonium bromide (CTAB)‐catalyzed modified protocol. This protocol provided 78%–90% yields of novel aryl‐substituted triazole derivatives 11 ( a – g ) and 78%–95% yields of carbazole‐based benzofuran‐substituted triazole derivatives 9 ( a – j ). The synthesized derivatives were characterized and subjected to in silico biological evaluation against the NS5A and NS5B HCV proteins. The molecular dynamics simulation was also carried out to elucidate the stability of selected proteins via RMSD, RMSF, and protein–ligand interactions. Furthermore, the density functional theory studies of carbazole derivatives were employed to demonstrate the frontier molecular orbitals (HOMO and LUMO), Mulliken charge distribution, and molecular electrostatic potential (MEP) map surface to provide insights into the electronic structure and properties of the target compounds. The pharmacokinetic profile of potent compounds has also been provided to elucidate their drug‐like parameters.