Novel hybrid structures based on 4-Chlorobenzenesulfonyl and 1,2,3-triazoles: Synthesis, in vitro biological activities and in silico studies

Abstract

New hybrid structures containing 4-chlorosulfonamide and 1,2,3-triazole units were designed and synthesized. Antioxidant, cholinesterase (AChE and BuChE) and anticancer activities of these hybrid structures were investigated. Especially the DPPH activity of compound 8a (IC50: 8.659 μg/mL) was found to be higher than ascorbic acid (IC50: 4.780 μg/mL), α-Tocopherol (IC50: 9.229 μg/mL) and BHT (IC50: 7.948 μg/mL). Compounds 8d, 8 g and 8b also had good activity values. The anticancer activities of the hybrid structures were determined using PC3 (prostate cancer) and Caco-2 (colon adenocarcinoma) cell lines. 5-Fu (IC50: 4.34 ± 1.29) was used as standard. Compounds 8c (IC50: 3.82 ± 1.86 µM) for PC3 and 8 h (IC50: 6.39 ± 1.14 µM) for Caco-2 were found to have outstanding activity values. All synthesized compounds’ AChE and BuChE inhibitory activities were determined using Galantamine as a standard. Especially 8b (IC50: 0.29 ± 0.003 mM) had about 28 times better activity than the standard Galantamine (IC50: 8 ± 0.05 mM). After a thorough examination, the ADMET properties of the molecules were found to meet the rigorous standards required for pharmaceutical applicability. Furthermore, their impressive oral absorption capability is linked to their ability to effectively navigate the blood–brain barrier and the gastrointestinal tract. In-vitro evaluations were further validated through molecular docking studies conducted in silico.