Visible Light-Promoted Green and Sustainable Approach for One-Pot Synthesis of 4,4’-(Arylmethylene)bis(1H-pyrazol-5-ols), In Vitro Anticancer Activity, and Molecular Docking with Covid-19 M^pro

Abstract

A visible light-promoted, efficient, green, and sustainable strategy has been adopted to unlatch a new pathway toward the synthesis of a library of medicinally important 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) moieties using substituted aromatic aldehydes and sterically hindered 3-methyl-1-phenyl-2-pyrazoline-5-one in excellent yield. This reaction shows high functional group tolerance and provides a cost-effective and catalyst-free protocol for the quick synthesis of biologically active compounds from readily available substrates. Synthesized compounds were characterized by spectroscopic techniques such as IR, ¹HNMR, ¹³CNMR, and single-crystal XRD analysis. All the synthesized compounds were evaluated for their antiproliferative activities against a panel of five different human cancer cell lines and compared with Tamoxifen using MTT assay. Compound <b>3m</b> exhibited maximum antiproliferative activity and was found to be more active as compared to Tamoxifen against both the MCF-7 and MDA-MB-231 cell lines with an IC₅₀ of 5.45 and 9.47 μM, respectively. A molecular docking study with respect to COVID-19 main protease (M^pro) (PDB ID: 6LU7) has also been carried out which shows comparatively high binding affinity of compounds <b>3f</b> and <b>3g</b> (-8.3 and -8.8 Kcal/mole, respectively) than few reported drugs such as ritonavir, remdesivir, ribacvirin, favipiravir, hydroxychloroquine, chloroquine, and olsaltamivir. Hence, it reveals the possibility of these compounds to be used as effective COVID-19 inhibitors.