Sahin_2023_J.Biomol.Struct.Dyn__1

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 (IC(50): 229.46 +/- 0.001 microg/mL) and 9h (IC(50): 254.32 +/- 0.002 microg/mL) hybrid structures were higher than BHT (IC(50): 286.04 +/- 0.003 microg/mL) and lower than Ascorbic acid (IC(50): 63.53 +/- 0.001 microg/mL) and alpha-Tocopherol (IC(50): 203.21 +/- 0.002 microg/mL). We determined that the cytotoxic effects of hybrid constructs 9d (IC(50): 3.81 +/- 0.1084 microM) and 9g (IC(50): 4.317 +/- 0.0367 microM) against A549 and healthy cell line (HDF) are much better than standard cisplatin (IC(50): 6.202 +/- 0.0705 microM). It was determined that the AChE inhibitory activities of all synthesized compounds were much better than Galantamine used as a standard. In particular, 9c (IC(50): 13.81 +/- 0.0026 mM) had ten times better activity than the standard Galantamine (IC(50): 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.