{"title":"In Silico ADME, DFT, and Antiproliferative Activity of Pyrazole-based Pyrimidinethione, Triazolethione, and Thiadiazolopyrimidine Derivatives","authors":"S. K. Ramadan, S. M. Gomha, E. A. E. El-Helw","doi":"10.1134/S1070363224612146","DOIUrl":null,"url":null,"abstract":"<p>Some pyrazole-based pyrimidinethione, triazolethione, and thiadiazolopyrimidine candidates, exhibiting good antioxidant properties, were evaluated for their in vitro antiproliferative activity against breast and colon cancer cell lines. The most potency was displayed by triazolethione and thiadiazolopyrimidine derivatives. According to density-functional theory, the former exhibited high electrophilicity and revealed the lowest energy gap and hardness, and the highest softness, being more reasonable toward radical surface interactions. Also, these two compounds showed good docking simulation towards cyclin-dependent kinase-2 (CDK2) protein compared to doxorubicin and co-crystallized ligand. Among modeling pharmacokinetics, all compounds exhibited good bioavailability and lead-likeness. It is hoped that this work may contribute to developing new potent antiproliferative agents.</p>","PeriodicalId":761,"journal":{"name":"Russian Journal of General Chemistry","volume":"95 2","pages":"491 - 504"},"PeriodicalIF":0.9000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Russian Journal of General Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1134/S1070363224612146","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Some pyrazole-based pyrimidinethione, triazolethione, and thiadiazolopyrimidine candidates, exhibiting good antioxidant properties, were evaluated for their in vitro antiproliferative activity against breast and colon cancer cell lines. The most potency was displayed by triazolethione and thiadiazolopyrimidine derivatives. According to density-functional theory, the former exhibited high electrophilicity and revealed the lowest energy gap and hardness, and the highest softness, being more reasonable toward radical surface interactions. Also, these two compounds showed good docking simulation towards cyclin-dependent kinase-2 (CDK2) protein compared to doxorubicin and co-crystallized ligand. Among modeling pharmacokinetics, all compounds exhibited good bioavailability and lead-likeness. It is hoped that this work may contribute to developing new potent antiproliferative agents.
期刊介绍：
Russian Journal of General Chemistry is a journal that covers many problems that are of general interest to the whole community of chemists. The journal is the successor to Russia’s first chemical journal, Zhurnal Russkogo Khimicheskogo Obshchestva (Journal of the Russian Chemical Society ) founded in 1869 to cover all aspects of chemistry. Now the journal is focused on the interdisciplinary areas of chemistry (organometallics, organometalloids, organoinorganic complexes, mechanochemistry, nanochemistry, etc.), new achievements and long-term results in the field. The journal publishes reviews, current scientific papers, letters to the editor, and discussion papers.
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