Publication: Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives
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Issued Date
2022
Resource Type
Language
eng
File Type
application/pdf
ISSN
24058440
Rights Holder(s)
Scopus
Bibliographic Citation
Scientific Reports. Vol 12, No.1 (2022)
Suggested Citation
Pingaew R., Prachayasittikul V., Worachartcheewan A., Thongnum A., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives. Scientific Reports. Vol 12, No.1 (2022). doi:10.1016/j.heliyon.2022.e10067 Retrieved from: https://hdl.handle.net/20.500.14740/10005
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: Rtr range = 0.8301–0.9636 and RMSEtr = 0.0666–0.2680; leave-one-out cross validation sets: RCV range = 0.7628–0.9290 and RMSECV = 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. © 2022