Potential COVID-19 Drug Candidates Based on Diazinyl-Thiazol-Imine Moieties: Synthesis and Greener Pastures Biological Study.

Sraa Abu-Melha,Nadia S Al-Kaff,Sobhi M Gomha,Musa A Said,Sayed M Riyadh,Mastoura Mohamed Edrees

doi:10.3390/molecules27020488

Abstract

A novel series of 1-aryl-N-[4-phenyl-5-(arylazo)thiazol-2-yl)methanimines has been synthesized via the condensation of 2-amino-4-phenyl-5-arylazothiazole with various aromatic aldehydes. The synthesized imines were characterized by spectroscopic techniques, namely 1H and 13C-NMR, FTIR, MS, and Elemental Analysis. A molecular comparative docking study for 3a–f was calculated, with reference to two approved drugs, Molnupiravir and Remdesivir, using 7BQY (Mpro; PDB code 7BQY; resolution: 1.7 A°) under identical conditions. The binding scores against 7BQY were in the range of −7.7 to −8.7 kcal/mol for 3a–f. The high scores of the compounds indicated an enhanced binding affinity of the molecules to the receptor. This is due to the hydrophobic interactions and multi-hydrogen bonds between 3a–f ligands and the receptor’s active amino acid residues. The main aim of using in silco molecular docking was to rank 3a–f with respect to the approved drugs, Molnupiravir and Remdesivir, using free energy methods as greener pastures. A further interesting comparison presented the laydown of the ligands before and after molecular docking. These results and other supporting statistical analyses suggested that ligands 3a–f deserve further investigation in the context of potential therapeutic agents for COVID-19. Free-cost, PASS, SwissADME, and Way2drug were used in this research paper to determine the possible biological activities and cytotoxicity of 3a–f.

Highlights

Since the appearance of COVID-19, followed by the Delta variant and recently the potentially more infectious Omicron strain pandemic caused by severe acute respiratory syndrome, the world has taken action for protection, such as emphasizing the importance of social distancing/masking [1,2]
The condensation of 2-amino-4-phenyl-5-arylazothiazole (1) with various aromatic aldehydes 2 in boiling ethanol and catalytic drops of piperidine resulted in the formation of the respective imine derivatives 3a–f, with electron-donating and electron-withdrawing groups on arylazo moiety (Scheme 1)
The results showed that the LD50 in parallel with the toxicity class for 3a–f and the approved medicine as a comparison

Summary

Introduction

Since the appearance of COVID-19, followed by the Delta variant and recently the potentially more infectious Omicron strain pandemic caused by severe acute respiratory syndrome, the world has taken action for protection, such as emphasizing the importance of social distancing/masking [1,2]. The good news is that various COVID-19 vaccines have been developed and evaluated at an extraordinary speed [3,4,5,6,7,8]. Having this in view, in this paper, we will test and evaluate our compounds by comparing their performances to the two well-established drugs (Molnupiravir and Remdesivir). An in silco method will be employed as a preliminary study to filter and rank our compounds as greener pastures at this stage [9,10,11]

Objectives

Methods

Results

Conclusion