A Comparative In Vitro Anticancer Evaluation and In Silico Study of New 1‐(1,3‐Oxazol‐5‐yl)piperidine‐4‐sulfonylamides

Abstract In this work, we synthesized a series of new 1,3‐oxazole derivatives comprising the sulfonylamide group and tested their activity against the human tumor cell line panel. This study further explores the stereoelectronic characteristics of 1,3‐oxazol‐5‐sulfonylamides and new 1‐(1,3‐oxazol‐5‐yl)piperidine‐4‐sulfonylamides to connect their anticancer activity to the molecular structure. Combining in vitro and in silico methods, we analyzed how the proximity of the sulfonylamide group to the heterocyclic ring affects the structure–activity interplay. Herein, our assessment is based on the purported complexation of 1,3‐oxazoles with targeted biomolecular fragments involving the π‐stacking interaction and hydrogen bonding within the prospective complexes. Defining the probability of the prospective drug–target interactions, we detail conformational properties, donor/acceptor capabilities, electronic characteristics, and thermodynamic preference of produced sulfanylamide group containing 1,3‐oxazoles toward biomolecular fragments, identifying the nature of variations in anticancer activity.