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 Mpro

Anamika Gupta; Safia Iqbal; Roohi; Mohd Kamil Hussain; Mohd Rehan Zaheer; Krapa Shankar

doi:10.1021/acsomega.2c04506

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

ACS Omega. 2022 Sep 14;7(38):34583-34598. doi: 10.1021/acsomega.2c04506. eCollection 2022 Sep 27.

Authors

Anamika Gupta¹, Safia Iqbal¹, Roohi², Mohd Kamil Hussain³, Mohd Rehan Zaheer⁴, Krapa Shankar⁵

Affiliations

¹ Department of Chemistry, Aligarh Muslim University, Aligarh202002, Uttar Pradesh, India.
² Protein Research Laboratory, Department of Bioengineering, Integral University, Lucknow226026, Uttar Pradesh, India.
³ Department of Chemistry, Govt. Raza PG College, Rampur24901, Uttar Pradesh, India.
⁴ Department of Chemistry, R.M.P.S.P. Girls Post Graduate College, Basti272301, Uttar Pradesh, India.
⁵ Sun Pharmaceutical industries Ltd, Sarhaul, Sector 18, Gurgaon, Haryana122015, India.

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 3m 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 3f and 3g (-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.