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

Abstract

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 μg/mL) and 9h (IC₅₀: 254.32 ± 0.002 μg/mL) hybrid structures were higher than BHT (IC₅₀: 286.04 ± 0.003 μg/mL) and lower than Ascorbic acid (IC₅₀: 63.53 ± 0.001 μg/mL) and α-Tocopherol (IC₅₀: 203.21 ± 0.002 μg/mL). We determined that the cytotoxic effects of hybrid constructs 9d (IC₅₀: 3.81 ± 0.1084 µM) and 9g (IC₅₀: 4.317 ± 0.0367 µM) against A549 and healthy cell line (HDF) are much better than standard cisplatin (IC₅₀: 6.202 ± 0.0705 µM). 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

Keywords:

• Triazole
• Alzheimer
• in silico

Acknowledgments

This study is dedicated to our esteemed colleague İrfan Şahin and his family, who lost their lives in the earthquake in Kahramanmaraş that occurred on February 6, 2023.

Authors’ Contributions

İ.Ş.; investigation, methodology, original draft preparation, writing, M.Ç.; in silico analysis, software, original draft preparation, writing-review, and editing, Ö. G.; enzyme inhibition analysis, F.B.Ö.; in vitro analysis, M. K.; X-ray analysis, FT; supervision, conceptualization, project administration, funding acquisition.

Disclosure Statement

The authors declare no conflict of interest.

Additional information

Funding

The authors thanks Kahramanmaras Sutcu Imam University Scientific Research Projects Unit (Project code: DOSAP-2021/3-33 D) (Turkey) for funding.