One-pot synthesis, molecular docking, ADMET, and DFT studies of novel pyrazolines as promising SARS-CoV-2 main protease inhibitors

Abstract

Pyrazoline and its derivatives have numerous prominent pharmacological effects. Focusing on its anti-viral property, we have designed and synthesized three novel pyrazoline derivatives ( A1–A3 ) through one-pot three components and characterized them using different spectroscopic techniques (FT-IR, 1 H NMR, 13 C NMR, and UV). These compounds were evaluated against SARS-CoV-2 main protease utilizing in-silico molecular docking studies. The docking results displayed good inhibitory activity of the synthesized compounds. Among them, compound A2 was the most active against targeted protein. The drug-likeness and ADMET properties were predicted to have varied profiles but could still be developed, especially A2 . DFT/TD-DFT calculations through B3LYP/6-311G++ level of theory were applied to provide comparable theoretical data along with MEP map and electronic energy gap of HOMO → LUMO. Supplementary Information The online version contains supplementary material available at 10.1007/s11164-022-04831-5.

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