Protic Ionic Liquid Promoted One Pot Synthesis of 2‐amino‐4‐(phenyl)‐7‐methyl‐5‐oxo‐4H,5H‐pyrano[4,3‐b]pyran‐3‐carbonitrile Derivatives in Water and Their Antimycobacterial Activity

Abstract

in Wiley Online Library (wileyonlinelibrary.com).One pot three component reaction of 4-hydroxy-6-methylpyran-2-one, 3-methoxy benzaldehyde, and malononitrile in water using protic ionic liquid as a catalyst at room temperature afforded pyrano[4,3-b]pyran derivatives. Protic ionic liquid has been proved to be an efficient and mild catalyst for the synthesis of pyrano[4,3-b]pyran scaffolds due to their highly polar nature. The notable aspects of protic ionic liquid are easy availability, improved reaction rates, high product yields, simple workup procedure, recyclability, and reusability. Molecules docking studies have been performed on enzyme enoyl-ACP-reductase from Mycobacterium tuberculosis. The molecular docking simulation indicated plausible π-alkyl and alkyl-alkyl interactions between the amino acids and scaffolds. The synthesized derivatives have been evaluated for their in vitro antituberculotic activity against M. tuberculosis H 37 RV strain using Microplate Alamar Blue Assay method. Together, biological activity data and docking data showed that the tested scaffolds exhibited excellent antituberculotic activity.

Predictive Power of In Silico Approach to Evaluate Chemicals against M. tuberculosis: A Systematic Review

“…However, mutations in KatG/EthA have been reported and correlated with the development of Mtb resistance to INH and ETH [31,32], thus leading to the need for new molecules that can either directly inhibit the InhA enzyme or find novel molecular paths that can ultimately promote bacterium eradication. Within the 46 manuscripts, the Enoyl-[acyl-carrier-protein] reductase (NADH) (EC 1.3.1.9) was evaluated nine times [10,15,33,34,35,36,37,38,39]. All analyzed articles were able to correctly dock their postulated inhibitors on different sites of the enzyme and studied the obtained results with in vitro assays.…”

“…Through our screening process, we retrieved 46 documents, ranging from 2005 to 2018, which are described in Figure 4. Two manuscripts were from 2005 [9,53]; one each was from 2007 [60], 2008 [64], and 2009 [65]; two each were from 2011 [34,55] and 2012 [36,63]; five were from 2013 [10,26,35,38,70]; 10 were from 2014 [14,16,23,44,45,46,49,58,66]; nine were from 2015 [6,11,12,15,47,48,50,56,67]; six were from 2016 [13,33,54,57,61,69]; five were from 2017 [21,22,39,59,68]; and finally, only two were from 2018 [37,62].…”

“…Virtual screening (VS) methods used on the analyzed manuscripts. References for ligand-based VS: [6,11,12,13,22,23,35,36,37,39,45,47,54,55,58,59,60,62,68,69]; structure-based VS: [9,10,14,16,26,33,34,44,46,48,49,50,53,56,57,61,63,64,65] and both ligand and structure-based VS [15,21,38,66,67,70]. …”

“…The ligand databases used most for screening. References: No database [15,22,23,33,35,36,37,39,47,54,58,62,68,69]; ZINC [11,21,26,38,55,63,66,67]; in-house [9,45,53,57,64]; Chembridge [6,10,13,34]; Maybridge [12,65,67,70]; BITS Pilani [44,48,56]; Asinex[14,46,48]; Collaborative Drug Discovery Database [49,50]; Other (CDRI [60], FDA approved drugs [67], ChemDiv [6], ChemSpider [59], TAACF [16], GSK [16], Enamine REAL [61], NCI [21] and Specs [70]).…”

“…The most used docking software. References: Glide [6,11,13,14,15,16,36,39,44,46,47,48,56,62,68,69,70]; Autodock (v.3 or 4) [9,12,21,22,37,38,53,54,59,64,67]; GOLD [9,10,14,26,34,38,56]; FlexX [12,60,62,65]; Surflex Dock [12,23,33,62]; Autodock VINA [31,47]; DOCK [34,57]; LibDock [49,50]; FRIGATE [55,63] and Other (Biopredicta [58]; Surflex-geomx [12]; CDOCKER [61]; SABRE [66]; Argus Dock [35]).…”