Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (Mpro).

Sraa Abu-Melha,Mohamad R Abdelaziz,Mastoura M Edrees,Sayed M Riyadh,Sobhi M Gomha,Abdo A Elfiky

doi:10.3390/molecules25194565

Abstract

A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (−8.1 ± 0.33 kcal/mol, −8.0 ± 0.35 kcal/mol, and −8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (−6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.

Highlights

Clean chemistry is a multidisciplinary concept for the judicious use of chemical reactions and prevents its pollution
[2,18,19,20,21,22,23], we propose an easy, efficient, solid-state continuation of our interest in green synthesis of heterocycles [2,18,19,20,21,22,23], we propose an easy, grinding for the preparation of hydrazones
The structures are tested for their anti-viral activity against SARS-CoV-2 main protease (Mpro ) using molecular docking combined with molecular dynamics simulation (MDS) for up to 100 nanoseconds

Summary

Introduction

Clean chemistry is a multidisciplinary concept for the judicious use of chemical reactions and prevents its pollution. It involves the designing of chemical products by using environmentally safe procedures that reduce the generation of hazardous substances, as well as the cost [1]. Hydrazone is an effective nucleus because hydrazine-containing compounds (R1 R2 C=NNH-R3 ) offer a wide range of biological activities, Molecules 2020, 25, 4565; doi:10.3390/molecules25194565 www.mdpi.com/journal/molecules. Hydrazone is an effective nucleus because hydrazine-containing compounds (R1R2C=NNH-R3) offer a wide range of biological activities, including anticholinesterase [6], antimycobacterial [7], anti-cancer [8], antibacterial, including anticholinesterase [6], antimycobacterial [7], anti-canceranalgesic,.

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Conclusion