New sulfonamide derivatives based on 1,2,3-triazoles: synthesis, in vitro biological activities and in silico studies

Eight new hybrid constructs containing a series of sulfonamide and 1,2,3-triazole units were designed and synthesized. Anticancer, antioxidant and cholinesterase activities of these hybrid structures were investigated. In our design, the Cu(I)-catalyzed click reaction between N,4-dimethyl-N-(prop-2-yn-1-yl)benzenesulfonamide (6) and aryl azides 8a-h was used. Antioxidant activity values of 9f (IC50: 229.46 +/- 0.001 mu g/mL) and 9h (IC50: 254.32 +/- 0.002 mu g/mL) hybrid structures were higher than BHT (IC50: 286.04 +/- 0.003 mu g/mL) and lower than Ascorbic acid (IC50: 63.53 +/- 0.001 mu g/mL) and alpha-Tocopherol (IC50: 203.21 +/- 0.002 mu g/mL). We determined that the cytotoxic effects of hybrid constructs 9d (IC50: 3.81 +/- 0.1084 mu M) and 9g (IC50: 4.317 +/- 0.0367 mu M) against A549 and healthy cell line (HDF) are much better than standard cisplatin (IC50: 6.202 +/- 0.0705 mu M). It was determined that the AChE inhibitory activities of all synthesized compounds were much better than Galantamine used as a standard. In particular, 9c (IC50: 13.81 +/- 0.0026 mM) had ten times better activity than the standard Galantamine (IC50: 136 +/- 0.008 mM). The ADMET properties of the molecules have been thoroughly examined and met the criteria for drug-like substances. They also have a high oral absorption rate, as they can effectively cross the blood-brain barrier and are easily absorbed in the gastrointestinal tract. In vitro experiments were confirmed by in silico molecular docking studies.Communicated by Ramaswamy H. Sarma