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

• Main Authors: Salih, Rezan Huseen Hama, Hasan, Aso Hameed, Hussein, Awaz Jamil, Samad, Mohammed Kareem, Shakya, Sonam, Jamalis, Joazaizulfazli, Hawaiz, Farouq Emam, Pratama, Mohammad Rizki Fadhil
• Format: Article
• Language: English
• Published: Springer Science and Business Media B.V. 2022
• Subjects: QD Chemistry
• Online Access: http://eprints.utm.my/103922/1/JoazaizulfazliJamalis2022_OnePotSynthesisMolecularDockingADMET.pdf; http://eprints.utm.my/103922/; http://dx.doi.org/10.1007/s11164-022-04831-5
• Institution: Universiti Teknologi Malaysia

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, 1H NMR, 13C 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.