{"title":"Synthesis and Exploring Antiproliferative Activity of Some Pyrazole-Bearing Heterocycles: DFT, Molecular Docking, and ADME Study","authors":"S. K. Ramadan, S. M. Gomha, E. A. E. El-Helw","doi":"10.1134/S1070363225600134","DOIUrl":null,"url":null,"abstract":"<p>Worldwide, millions of people are impacted by cancer. In vitro antiproliferative activity of some pyrazole-bearing <i>N</i>-heterocycles was tested against HCT116 and MCF7 cancer cell lines, which showed the most efficacy of pyranoquinoline and chromene. Among molecular docking simulation towards cyclin-dependent kinase-2 (CDK2) protein, pyranoquinoline had the best docking, compared to doxorubicin and roscovitine (RRC), hinting at a possible mechanism of action (interactions with common amino acids). DFT simulation displayed unprecedented insights into these compounds' electronic properties and structure-activity relationships. Pyranoquinoline had the greatest softness and the lowest energy gap, increasing its reactivity to radical surface interactions. Compounds with notable antiproliferative activity were those with high electrophilicity values. Modeling pharmacokinetics simulation also revealed the ideal drug-likeness and oral bioavailability features of compounds. This research may aid in the creation of innovative, highly effective agents used in the battle against cancer and other infections in the future.</p>","PeriodicalId":761,"journal":{"name":"Russian Journal of General Chemistry","volume":"95 3","pages":"732 - 741"},"PeriodicalIF":0.8000,"publicationDate":"2025-03-27","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/S1070363225600134","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
Worldwide, millions of people are impacted by cancer. In vitro antiproliferative activity of some pyrazole-bearing N-heterocycles was tested against HCT116 and MCF7 cancer cell lines, which showed the most efficacy of pyranoquinoline and chromene. Among molecular docking simulation towards cyclin-dependent kinase-2 (CDK2) protein, pyranoquinoline had the best docking, compared to doxorubicin and roscovitine (RRC), hinting at a possible mechanism of action (interactions with common amino acids). DFT simulation displayed unprecedented insights into these compounds' electronic properties and structure-activity relationships. Pyranoquinoline had the greatest softness and the lowest energy gap, increasing its reactivity to radical surface interactions. Compounds with notable antiproliferative activity were those with high electrophilicity values. Modeling pharmacokinetics simulation also revealed the ideal drug-likeness and oral bioavailability features of compounds. This research may aid in the creation of innovative, highly effective agents used in the battle against cancer and other infections in the future.
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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