Synthesis of New Binary Thiazole-Based Heterocycles and Their Molecular Docking Study as COVID-19 Main Protease (Mpro) Inhibitors

Abstract

Isolated polynuclear binary heterocyclic compounds containing thiazole building block combined with benzofuran, pyrrole, thiazole, or thiophene via carboxamide and/or secondary amine as a junction are presented. The synthetic strategy of those is based on utilization of 2-chloroacetamido-4-phenylthiazole in the synthesis of binary heterocyclic compounds by cyclocondensation with salicylic aldehyde, acetonitrile derivatives, ammonium thiocyanate, 3-mercaptoacrylonitrile derivatives, and/or 3-mercaptoacrylate derivatives. The prepared binary thiazole-based heterocycles have been studied as protease (M pro ) inhibitors by molecular docking for visualization of their orientation and interactions with COVID-19 units using hydroxychloroquine as a reference molecule.

Isolation of Thioinosine and Butenolides from a Terrestrial Actinomycetes sp. GSCW‐51 and Their in Silico Studies for Potential against SARS‐CoV‐2

“…For instance, thiazole-based heterocyclic compounds as synthesized and docked against Mpor enzyme showed binding energies ranging from À 4.1 (compound 1) to À 8.5 kcal/mol (compound 15). [39] The binding energy of our best docked complex in terms of E-score is also comparable to azo imidazole derivative (L3 = À 6.7 kcal/mol), [40] Chloroquine (À 5.3 kcal/mol), 6-Gingerol (À 5.8 kcal/mol) and Myristicin (À 5.3 kcal/mol) etc. [41] It is important to pen down that this semi-quantitative comparison based only on binding energies as calculated through similar protocols using grid based docking techniques.…”

“…Furthermore, it will be also interesting to compare the calculated binding energies of above entitled compounds with those of other similar studies. For instance, thiazole‐based heterocyclic compounds as synthesized and docked against Mpor enzyme showed binding energies ranging from −4.1 (compound 1 ) to −8.5 kcal/mol (compound 15 ) [39] . The binding energy of our best docked complex in terms of E‐score is also comparable to azo imidazole derivative (L3=−6.7 kcal/mol), [40] Chloroquine (−5.3 kcal/mol), 6‐Gingerol (−5.8 kcal/mol) and Myristicin (−5.3 kcal/mol) etc [41] .…”

Computational molecular docking and in silico ADMET prediction studies of pyrazole derivatives as Covid-19 main protease (MPRO) and papain-like protease (PLPRO) inhibitors

“…Hydroxychloroquine during the last few months was considered a promised candidate drug for Covid-19 [32]. The inhibition of M pro presents a unique challenge in which the active site pocket is characteristically and in continuation of our work [33] to discover new drug enzyme interaction we presented this study.…”

Zeolite A/ZnCl2 nanoparticles as a catalyst for eco-friendly synthesis of pyrazole-1- carbothioamides with docking validation as Covid-19 main protease (MPRO) inhibitor

“…Utilizing catalysis in organic reactions is an endlessly fascinating and ever-changing phenomenon. My research team is continuously looking for new catalysts to characterise and use in the advancement of organic synthesis [32][33][34][35]. In this paper, we present a new type of catalyst that can be used to synthesis pyrazole-1-carbothioamides, an important class of organic compounds.…”