Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives

Ratchanok Pingaew; Veda Prachayasittikul; Apilak Worachartcheewan; Anusit Thongnum; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul

doi:10.1016/j.heliyon.2022.e10067

Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives

Heliyon. 2022 Aug 2;8(8):e10067. doi: 10.1016/j.heliyon.2022.e10067. eCollection 2022 Aug.

Authors

Ratchanok Pingaew¹, Veda Prachayasittikul², Apilak Worachartcheewan³, Anusit Thongnum⁴, Supaluk Prachayasittikul², Somsak Ruchirawat^{5

6

7}, Virapong Prachayasittikul⁸

Affiliations

¹ Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
² Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
³ Department of Community Medical Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
⁴ Department of Physics, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
⁵ Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.
⁶ Program in Chemical Sciences, Chulabhorn Graduate Institute, Bangkok 10210, Thailand.
⁷ Center of Excellence on Environmental Health and Toxicology (EHT), Commission on Higher Education, Ministry of Education, Bangkok 10400, Thailand.
⁸ Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.

Abstract

Sulfur-containing compounds are considered as attractive pharmacophores for discovery of new drugs regarding their versatile properties to interact with various biological targets. Quantitative structure-activity relationship (QSAR) modeling is one of well-recognized in silico tools for successful drug discovery. In this work, a set of 38 sulfur-containing derivatives (Types I-VI) were evaluated for their in vitro anticancer activities against 6 cancer cell lines. In vitro findings indicated that compound 13 was the most potent cytotoxic agent toward HuCCA-1 cell line (IC₅₀ = 14.47 μM). Compound 14 exhibited the most potent activities against 3 investigated cell lines (i.e., HepG2, A549, and MDA-MB-231: IC₅₀ range = 1.50-16.67 μM). Compound 10 showed the best activity for MOLT-3 (IC₅₀ = 1.20 μM) whereas compound 22 was noted for T47D (IC₅₀ = 7.10 μM). Subsequently, six QSAR models were built using multiple linear regression (MLR) algorithm. All constructed QSAR models provided reliable predictive performance (training sets: R_tr range = 0.8301-0.9636 and RMSE_tr = 0.0666-0.2680; leave-one-out cross validation sets: R_CV range = 0.7628-0.9290 and RMSE_CV = 0.0926-0.3188). From QSAR modeling, chemical properties such as mass, polarizability, electronegativity, van der Waals volume, octanol-water partition coefficient, as well as frequency/presence of C-N, F-F, and N-N bonds in the molecule are essential key predictors for anticancer activities of the compounds. In summary, a series of promising fluoro-thiourea derivatives (10, 13, 14, 22) were suggested as potential molecules for future development as anticancer agents. Key structure-activity knowledge obtained from the QSAR modeling was suggested to be advantageous for suggesting the effective rational design of the related sulfur-containing anticancer compounds with improved bioactivities and properties.

Keywords: Anticancer activity; QSAR; Sulfonamide; Thiourea.