Phenothiazine and amide-ornamented dihydropyridines via a molecular hybridization approach: design, synthesis, biological evaluation and molecular docking studies

Abstract

A series of novel phenothiazinyldihydropyridine dicarboxamides 7a–7j was synthesized by adopting a multi-step synthetic strategy and characterized through physical and spectral techniques. Among them, the chemical entities with para-fluoro (7d), ortho-bromo and -fluoro (7f and 7i), ortho- and para-methyl (7e) and meta- and para-methoxy (7h) substituents exhibited either similar or superior anti-inflammatory activities with respect to the standard drug diclofenac sodium. Besides, the chemical entities with ortho-bromo and -fluoro substituents as well as meta-nitro substituents (7f, 7g and 7i) showed enhanced radical scavenging activities when compared to standard ascorbic acid. Furthermore, anticancer studies revealed that the meta- and para-chloro-substituted molecule 7a exerted the best activity against all the pancreatic cancer cells tested. Also, appreciable binding affinity (−8.10 kcal mol⁻¹) was observed during molecular docking between B-cell lymphoma 2 and 7a. The structural diversifications of the potent chemical entities besides further exploration in connection with the biological profiles of the same are underway.