Synthesis, antioxidant, antimicrobial and antiviral docking studies of ethyl 2-(2-(arylidene)hydrazinyl)thiazole-4-carboxylates

Abstract

A series of ethyl 2-(2-(arylidene)hydrazinyl)thiazole-4-carboxylates (2a–r) was synthesized in two steps from thiosemicarbazones (1a–r), which were cyclized with ethyl bromopyruvate to ethyl 2-(2-(arylidene)hydrazinyl)thiazole-4-carboxylates (2a–r). The structures of compounds (2a–r) were established by FT-IR, 1H- and 13C-NMR. The structure of compound 2a was confirmed by HRMS. The compounds (2a–r) were then evaluated for their antimicrobial and antioxidant assays. The antioxidant studies revealed, ethyl 2-(2-(4-hydroxy-3-methoxybenzylidene)hydrazinyl)thiazole-4-carboxylate (2g) and ethyl 2-(2-(1-phenylethylidene)hydrazinyl)thiazole-4-carboxylate (2h) as promising antioxidant agents with %FRSA: 84.46 ± 0.13 and 74.50 ± 0.37, TAC: 269.08 ± 0.92 and 269.11 ± 0.61 and TRP: 272.34 ± 0.87 and 231.11 ± 0.67 μg AAE/mg dry weight of compound. Beside bioactivities, density functional theory (DFT) methods were used to study the electronic structure and properties of synthesized compounds (2a–m). The potential of synthesized compounds for possible antiviral targets is also predicted through molecular docking methods. The compounds 2e and 2h showed good binding affinities and inhibition constants to be considered as therapeutic target for Mpro protein of SARS-CoV-2 (COVID-19). The present in-depth analysis of synthesized compounds will put them under the spot light for practical applications as antioxidants and the modification in structural motif may open the way for COVID-19 drug.

Synthesis of Arylidenehydrazinyl‐4‐methoxyphenylthiazole Derivatives: Docking Studies, Probing Type II Diabetes Complication Management Agents

“…The up‐field carbon signals in range δ 55.3–56.2 ppm were assigned to the methoxy carbons. The synthesis of compounds was further confirmed when NMR spectra were compared with literature reported similar skeleton compounds [38–45] …”

“…The synthesis of compounds was further confirmed when NMR spectra were compared with literature reported similar skeleton compounds. [38][39][40][41][42][43][44][45] After establishing the synthesis of the expected hydrazinyl-4-methoxyphenylthiazoles their biological significance was investigated by α-amylase inhibitory potential, antiglycation activity, antioxidant potential and cytotoxic behaviour by haemolytic assay.…”

Synthesis, SARS‐CoV‐2 3CL main protease inhibitor, anti‐inflammatory, and wound‐healing effects of a zinc(II)‐thiosemicarbazone complex

“…It was shown that some thiosemicarbazone compounds have antiviral effects on the SARS-CoV-2 as bioinformatically. [31][32][33] The effects of complex 2 on cell viability in BEAS-2B cells were measured by MTT cell viability test. As a result of the experiments, it was found that 2 had a proliferative effect at low doses.…”

“…It was shown that some thiosemicarbazone compounds have antiviral effects on the SARS‐CoV‐2 as bioinformatically. [ 31–33 ]…”

Introductory Chapter: Azoles, Their Importance, and Applications

“…Various oxygen-containing azoles, as exemplified by oxadiazoles, oxazoles, and isoxazoles, have been also thoroughly studied for their diversified biological activities. Widely used as potent antifungal agents (fungicides) due to their valuable properties like broad spectrum of action, chemical stability, and oral bioavailability [39][40][41][42], various azole derivatives have also demonstrated many other promising biological properties including antidiabetic, immunosuppressant, antiinflammatory, antiviral, antitubercular, and anticancer activities [8,12,[42][43][44][45][46].…”