{"title":"DFT studies of camptothecins cytotoxicity III: camptothecin, irinotecan and SN-38","authors":"M. Štekláč, M. Breza","doi":"10.2139/ssrn.4083390","DOIUrl":null,"url":null,"abstract":"Abstract Geometries of camptothecin, irinotecan, SN-38, and of their hypothetical Cu(II) complexes were optimized at the B3LYP/6-311G* level of theory. Their electron structure, evaluated in terms of Mulliken population analysis and Quantum Theory of Atoms-in-Molecule, was subsequently related to in vitro cytotoxicity. Electron density transfer from the relevant active sites to Cu decreases in the sequence irinotecan > SN-38 > camptothecin. The absolute values of their metal-ligand interaction energies exhibit the same trend. Discrepancy with the least relative in vitro cytotoxicity of irinotecan can be explained by differences in its pharmacokinetics.","PeriodicalId":7088,"journal":{"name":"Acta Chimica Slovaca","volume":"15 1","pages":"72 - 84"},"PeriodicalIF":0.9000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Chimica Slovaca","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2139/ssrn.4083390","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 1
Abstract
Abstract Geometries of camptothecin, irinotecan, SN-38, and of their hypothetical Cu(II) complexes were optimized at the B3LYP/6-311G* level of theory. Their electron structure, evaluated in terms of Mulliken population analysis and Quantum Theory of Atoms-in-Molecule, was subsequently related to in vitro cytotoxicity. Electron density transfer from the relevant active sites to Cu decreases in the sequence irinotecan > SN-38 > camptothecin. The absolute values of their metal-ligand interaction energies exhibit the same trend. Discrepancy with the least relative in vitro cytotoxicity of irinotecan can be explained by differences in its pharmacokinetics.