Synthesis, antioxidant, antimicrobial and antiviral docking studies of ethyl 2-(2-(arylidene)hydrazinyl)thiazole-4-carboxylates
Muhammad Haroon, Tashfeen Akhtar, Muhammad Khalid, Shehbaz Ali, Saniya Zahra, Ihsan ul Haq, Muhanad Alhujaily, Mabilly C. H. de B. Dias, Ana Cristina Lima Leite, Shabbir Muhammad
Abstract
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, 1 H- and 13 C-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 M pro 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.