Synthesis of acetamidosulfonamide derivatives with antioxidative and QSAR studies

Apilak Worachartcheewan; Somchai Pisutjaroenpong; Ratchanok Pingaew; Supaluk Prachayasittikul; Suphakit Siriwong; Somsak Ruchirawat; Virapong Prachayasittikul

doi:10.17179/excli2021-4590

Synthesis of acetamidosulfonamide derivatives with antioxidative and QSAR studies

EXCLI J. 2022 Feb 1:21:360-379. doi: 10.17179/excli2021-4590. eCollection 2022.

Authors

Apilak Worachartcheewan¹, Somchai Pisutjaroenpong², Ratchanok Pingaew³, Supaluk Prachayasittikul⁴, Suphakit Siriwong¹, Somsak Ruchirawat^{2

5

6}, Virapong Prachayasittikul⁷

Affiliations

¹ Department of Community Medical Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
² Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.
³ Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
⁴ Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
⁵ Program in Chemical Science, Chulabhorn Graduate Institute, Bangkok 10210, Thailand.
⁶ Center of Excellence on Environmental Health and Toxicology, Commission on Higher Education (CHE), Ministry of Education, Thailand.
⁷ Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.

Abstract

A series of sixteen acetamidosulfonamide derivatives (1-16) have been synthesized and investigated for their antioxidant (radical scavenging and superoxide dismutase (SOD)) and antimicrobial activities. Most compounds exhibited antioxidant activities in which compound 15 displayed the most potent radical scavenging and SOD activities. Quantitative structure-activity relationship (QSAR) has been studied using multiple linear regression. The constructed QSAR models displayed high correlation coefficient (Q ² _LOO-CV = 0.9708 and 0.8753 for RSA and SOD activities, respectively), but low root mean square error (RMSE _LOO-CV = 0.5105 and 1.3571 for RSA and SOD activities, respectively). The structure-activity relationship showed that an ethylene group connected to pyridine ring provided significant antioxidant activities. The QSAR models give insight into the rational designed of eighty new sulfonamides with various electron donating and withdrawing groups. The top five new designed sulfonamides with nitro group are potential antioxidants to be further developed for medicinal applications.

Keywords: QSAR; antioxidants; rational design; sulfonamides; superoxide dismutase.