喜树碱细胞毒性的DFT研究Ⅳ——伊立替康的活性和非活性形式

IF 0.9 Q4 CHEMISTRY, MULTIDISCIPLINARY Acta Chimica Slovaca Pub Date : 2023-01-01 DOI:10.2478/acs-2023-0001
M. Štekláč, M. Breza
{"title":"喜树碱细胞毒性的DFT研究Ⅳ——伊立替康的活性和非活性形式","authors":"M. Štekláč, M. Breza","doi":"10.2478/acs-2023-0001","DOIUrl":null,"url":null,"abstract":"Abstract Structures of irinotecan (CPT-11) in neutral lactone, neutral carboxyl, and anionic carboxylate forms in singlet ground states and of their complexes with Cu(II) in doublet ground states are optimized using B3LYP/6-311G* treatment. Metal ion affinities (MIA), Cu charges and Laplacians of Cu-ligand bond critical points of possible CPT active sites are evaluated. The formation of Cu(II) complexes with the anionic carboxylate ligand leads to the release of CO2 that can cause a decrease in the concentration of the active lactone form due to equilibria between all forms of the drug. MIA values and electron density transfer to Cu increase in the sequence lactone < neutral carboxyl < anionic carboxylate. Both neutral forms of irinotecan exhibit lower MIA values than those of camptothecin, unlike the anionic carboxylate form.","PeriodicalId":7088,"journal":{"name":"Acta Chimica Slovaca","volume":"16 1","pages":"1 - 11"},"PeriodicalIF":0.9000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"DFT studies of camptothecins cytotoxicity IV — active and inactive forms of irinotecan\",\"authors\":\"M. Štekláč, M. Breza\",\"doi\":\"10.2478/acs-2023-0001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract Structures of irinotecan (CPT-11) in neutral lactone, neutral carboxyl, and anionic carboxylate forms in singlet ground states and of their complexes with Cu(II) in doublet ground states are optimized using B3LYP/6-311G* treatment. Metal ion affinities (MIA), Cu charges and Laplacians of Cu-ligand bond critical points of possible CPT active sites are evaluated. The formation of Cu(II) complexes with the anionic carboxylate ligand leads to the release of CO2 that can cause a decrease in the concentration of the active lactone form due to equilibria between all forms of the drug. MIA values and electron density transfer to Cu increase in the sequence lactone < neutral carboxyl < anionic carboxylate. Both neutral forms of irinotecan exhibit lower MIA values than those of camptothecin, unlike the anionic carboxylate form.\",\"PeriodicalId\":7088,\"journal\":{\"name\":\"Acta Chimica Slovaca\",\"volume\":\"16 1\",\"pages\":\"1 - 11\"},\"PeriodicalIF\":0.9000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Chimica Slovaca\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2478/acs-2023-0001\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Chimica Slovaca","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2478/acs-2023-0001","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: 0

摘要

采用B3LYP/6-311G*处理,优化了伊立替康(CPT-11)单重态中性内酯、中性羧基和阴离子羧酸盐形态及其与Cu(II)双重态配合物的结构。评价了金属离子亲和力(MIA)、Cu电荷和CPT可能活性位点的Cu-配体键临界点laplacian。铜(II)配合物与阴离子羧酸配体的形成导致二氧化碳的释放,由于药物的所有形式之间的平衡,二氧化碳的释放会导致活性内酯形式的浓度降低。内酯<中性羧基<阴离子羧酸盐的MIA值和向Cu转移的电子密度增大。两种中性形式的伊立替康表现出比喜树碱更低的MIA值,不像阴离子羧酸形式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
DFT studies of camptothecins cytotoxicity IV — active and inactive forms of irinotecan
Abstract Structures of irinotecan (CPT-11) in neutral lactone, neutral carboxyl, and anionic carboxylate forms in singlet ground states and of their complexes with Cu(II) in doublet ground states are optimized using B3LYP/6-311G* treatment. Metal ion affinities (MIA), Cu charges and Laplacians of Cu-ligand bond critical points of possible CPT active sites are evaluated. The formation of Cu(II) complexes with the anionic carboxylate ligand leads to the release of CO2 that can cause a decrease in the concentration of the active lactone form due to equilibria between all forms of the drug. MIA values and electron density transfer to Cu increase in the sequence lactone < neutral carboxyl < anionic carboxylate. Both neutral forms of irinotecan exhibit lower MIA values than those of camptothecin, unlike the anionic carboxylate form.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Acta Chimica Slovaca
Acta Chimica Slovaca CHEMISTRY, MULTIDISCIPLINARY-
自引率
12.50%
发文量
11
期刊最新文献
Thermal- and light-induced SCO effect in Fe(II) complexes and coordination polymers Stability of ferrate during long-term storage Colour masterbatches and their use in polylactic acid fibres dyeing DFT studies of camptothecins cytotoxicity IV — active and inactive forms of irinotecan Utilization of Opuntia as an alternative ingredient in value added bread and pasta products
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1