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

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.

Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling

“…Hydrazones, which are employed in diverse domains of organic chemistry, are renowned for their versatility and are recognized as a significant category of compounds for new drug development . Hydrazones, which are regarded as a significant group of organic compounds, encompass CN bonds that are conjugated with the lone pair of electrons of a functional nitrogen atom, and possess the structure R 1 R 2 CNNH 2 , Nitrogen atoms exhibit nucleophilic properties, whereas carbon atoms possess both electrophilic and nucleophilic characteristics. , Hydrazone linkages in pharmaceutical materials have significant value in numerous transformations and have attracted great interest because of their many biological and clinical applications, such as anticancer, antimicrobial, antioxidant, antituberculosis, anti-inflammatory, antiviral, antiproliferative, and enzyme inhibitory activities. − …”

Synthesis and In Silico Study of Some New bis-[1,3,4]thiadiazolimines and bis-Thiazolimines as Potential Inhibitors for SARS-CoV-2 Main Protease

“…Moreover, azoles tethered imines are accentuated to investigate new potential drug candidates with diverse therapeutic efficacy such as antibacterial, antimicrobial, antifungal, anticancer, antioxidant, and antiproliferative activities [ 20 , 21 , 22 , 23 , 24 , 25 ]. So, molecular hybridization of imines and azoles is a beneficial approach to structural alteration, as a single species of two or more pharmacophores can serve as potential COVID-19 drug candidates [ 26 ].…”

Mechanochemical Synthesis of Fluorinated Imines

“…Due to its ability to undergo interactions with a wide range of biological targets, the imine function is an essential pharmacophore in nitrogen-containing bioactive compounds [6][7][8][9][10]. There are many different pharmacophores.…”