Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives
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 d...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402201355X |
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| author | Ratchanok Pingaew Veda Prachayasittikul Apilak Worachartcheewan Anusit Thongnum Supaluk Prachayasittikul Somsak Ruchirawat Virapong Prachayasittikul |
| author_facet | Ratchanok Pingaew Veda Prachayasittikul Apilak Worachartcheewan Anusit Thongnum Supaluk Prachayasittikul Somsak Ruchirawat Virapong Prachayasittikul |
| author_sort | Ratchanok Pingaew |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T06:04:04Z |
| format | Article |
| id | doaj.art-96cc75f6086442f2ad4e595cb165bedb |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-12T06:04:04Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
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| series | Heliyon |
| spelling | doaj.art-96cc75f6086442f2ad4e595cb165bedb2022-12-22T03:44:56ZengElsevierHeliyon2405-84402022-08-0188e10067Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivativesRatchanok Pingaew0Veda Prachayasittikul1Apilak Worachartcheewan2Anusit Thongnum3Supaluk Prachayasittikul4Somsak Ruchirawat5Virapong Prachayasittikul6Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand; Corresponding author.Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand; Corresponding author.Department of Community Medical Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, ThailandDepartment of Physics, Faculty of Science, Srinakharinwirot University, Bangkok 10110, ThailandCenter of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, ThailandLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand; Program in Chemical Sciences, Chulabhorn Graduate Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), Commission on Higher Education, Ministry of Education, Bangkok 10400, ThailandDepartment of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, ThailandSulfur-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.http://www.sciencedirect.com/science/article/pii/S240584402201355XThioureaSulfonamideAnticancer activityQSAR |
| spellingShingle | Ratchanok Pingaew Veda Prachayasittikul Apilak Worachartcheewan Anusit Thongnum Supaluk Prachayasittikul Somsak Ruchirawat Virapong Prachayasittikul Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives Heliyon Thiourea Sulfonamide Anticancer activity QSAR |
| title | Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives |
| title_full | Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives |
| title_fullStr | Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives |
| title_full_unstemmed | Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives |
| title_short | Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives |
| title_sort | anticancer activity and qsar study of sulfur containing thiourea and sulfonamide derivatives |
| topic | Thiourea Sulfonamide Anticancer activity QSAR |
| url | http://www.sciencedirect.com/science/article/pii/S240584402201355X |
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