Indole‐2‐carboxamides as New Anti‐Mycobacterial Agents: Design, Synthesis, Biological Evaluation and Molecular Modeling against mmpL3

Abstract

Tuberculosis (TB), an airborne disease caused by Mycobacterium tuberculosis, has infected millions of people and been responsible for their deaths. Toward the anti‐TB endeavor, the synthesis of total twenty‐four indole‐2‐carboxamide derivatives as potent anti‐TB agents have been carried out using CDI‐mediated amidation. The biological evaluation against H37Rv revealed compounds 5d, 5e and 5u with MICs in the range of 3.125‐12.5 μg/mL using MABA assay. Further, compound 5u was tested against RAW 264.7 cell by MTT assay and showed 32 % growth inhibitions. The structure activity relationship of the indole‐2‐carboxamides has been established for antimycobacterial activity. The physicochemical properties and ADMET parameters of the 5d, 5e and 5u using pKCSM and SwissADME revealed their suitability as promising drug candidates. Molecular docking studies using AutoDock Vina revealed binding of 5u with the catalytic site of mmpL3 (PDB ID: 6AJG). The MD simulations of the most active compound 5u using GROMACS 2020.1 revealed its stability at the protein active site. Further optimization of indole‐2‐carboxamies may reveal the potentiation of identified anti‐mycobacterial drug candidates.

Synthesis of Nitrogen- and Oxygen-Containing Heterocycles Catalysed by Metal Nanoparticles Reported in 2022

“…42 Several three-to seven-membered heterocyclic ring systems have been synthesised using MNPs as catalysts, as evident from the published literature from the scientific community. 43 As part of the on-going research endeavour from this laboratory for the synthesis of such heterocyclic scaffolds [44][45][46][47][48][49][50][51] with biological importance, [52][53][54][55] we provided a decennary report on MNP-catalysed synthesis of heterocycles published during 2010-2019, 49 and kept updating the same for 2020 50 and 2021. 45 Herein, we have provided further updates of the review on the metal nanoparticle-catalysed synthesis of aza-and oxa-heterocycles, with a primary focus on the mechanistic insights into MNPs and synthetic approaches to heterocyclic scaffolds, together with their elaborated understandings, reported during the calendar year 2022 (Table 1).…”

The Synthesis of Nitrogen- and Oxygen-Containing Heterocyclic Scaffolds Assisted by Ionic Liquids: A 2022 Literature Survey

“…In addition, various organic reactions such as 1,3-dipolar cycloaddition, 30 selective oxidation such as oxidative desulfurization, epoxidation of alkenes, Baeyer-Villiger oxidation, etc., 31 asymmetric syn-thesis, 32 alkylation of isoalkanes and alkenes, 33 Heck coupling, 34 Heck-Mizoroki coupling, 35 and Pd-catalyzed crosscoupling reactions have employed ILs. 36 As part of our ongoing synthetic endeavors for the synthesis of heterocycles, [37][38][39][40][41][42][43][44] we have reported the applications of ILs 45 for the synthesis of heterocycles accomplished between 2013 and 2020, 46 and later provided an update. 47 The present account provides an update of synthetic endeavors using ILs towards the preparation of heteroaromatic motifs reported across the globe, with the anticipation that it will provide wider benefits for the readership.…”

“…As part of our ongoing synthetic endeavors for the synthesis of heterocycles, 37 38 39 40 41 42 43 44 we have reported the applications of ILs 45 for the synthesis of heterocycles accomplished between 2013 and 2020, 46 and later provided an update. 47 The present account provides an update of synthetic endeavors using ILs towards the preparation of heteroaromatic motifs reported across the globe, with the anticipation that it will provide wider benefits for the readership.…”

“…Towards the on-going synthetic endeavor for the synthesis of heterocycles from this laboratory, [36][37][38][39][40][41][42][43] we have reported the applications of ILs 44 in the synthesis of heterocycles accomplished in 2013-2020 45 and updated it too. 46 Herein, the present work reports the update for the synthetic endeavor using ILs towards the synthesis of such heteroaromatic motifs reported across the globe with the anticipations to the next for the wider benefits of the reader of this work.…”

“…Pinate and Makone reported used the DABCO-based di-cationic acidic and recyclable (five times) ILs [C 4 H 10 -DABCO][HSO 4 ] 2 for the cycloaddition of 2-aminobenzenthiol (42) with α,β-enone (43) or substituted benzaldehyde (45) to yield 1,5-benzothiazepines (44) in 78-88% or 2-phenylbenzo[d]thiazoles (46) in 82-91% (Scheme 12). 68 These ILs were obtained by treating DABCO with 2-bromoethane afterward salt formation using conc.…”