Synthesis, Characterization, Antiproliferative Potential and Molecular Docking Studies of Novel Phenyl Sulfonyl Clubbed Benzothiazolyl Piperidine-3-Carboxamides

Global cancer incidence has approached nearly 21 million new cases annually and predicted to exceed 34 to 35 million new annual diagnoses by 2050. Benzothiazole is a vital privileged heterocyclic scaffold in anticancer drug discovery, as evident by Quizartinib (FDA-approved for acute myeloid leukemia) and Phortress (successful Phase I clinical trials against breast and ovarian cancers). In the present study, some novel benzothiazole derivatives 8(A-J) were designed and synthesized, based on the promising results obtained after structural modification of a multitargeted CDKs and VEGFR2 inhibitor, SNS-032. The compounds were investigated for their antiproliferative potential on a total of 60 cancer cell lines (NCI, USA) by sulforhodamine B (SRB) assay at 10 µM concentration. Compound 8 A exhibited good antiproliferative activity among all the compounds with good % growth inhibition (%GI) against cell lines of leukemia (SR, 82.73%; K-562, 73.48%; and MOLT-4, 70.32%), non-small cell lung cancer (HOP-92, 93.42%), and renal cancer (RXF 393, 85.12%). In molecular docking studies, 8 A was found to be active in comparison to the co-crystallized ligands against BCL-2 and mTOR anticancer drug targets. The predicted ADMET profile of all the compounds was found to be favorable in terms of toxicity, except slight hepatotoxicity and nephrotoxicity for 8 A.