Katarzyna Choroba, Bartosz Zowiślok, Sławomir Kula, Barbara Machura, Anna M. Maroń*, Karol Erfurt, Cristiana Marques, Sandra Cordeiro, Pedro V. Baptista and Alexandra R. Fernandes*,
{"title":"优化三亚胺铜(II)配合物的抗增殖特性","authors":"Katarzyna Choroba, Bartosz Zowiślok, Sławomir Kula, Barbara Machura, Anna M. Maroń*, Karol Erfurt, Cristiana Marques, Sandra Cordeiro, Pedro V. Baptista and Alexandra R. Fernandes*, ","doi":"10.1021/acs.jmedchem.4c0180610.1021/acs.jmedchem.4c01806","DOIUrl":null,"url":null,"abstract":"<p >Cu(II) complexes with 2,2′:6′,2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl<sub>2</sub>(L<sup><i>n</i></sup>)]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes (<b>Cu1a</b> and <b>Cu1b</b>) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. <b>Cu1a</b> and <b>Cu1b</b> do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"67 21","pages":"19475–19502 19475–19502"},"PeriodicalIF":6.8000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jmedchem.4c01806","citationCount":"0","resultStr":"{\"title\":\"Optimization of Antiproliferative Properties of Triimine Copper(II) Complexes\",\"authors\":\"Katarzyna Choroba, Bartosz Zowiślok, Sławomir Kula, Barbara Machura, Anna M. Maroń*, Karol Erfurt, Cristiana Marques, Sandra Cordeiro, Pedro V. Baptista and Alexandra R. Fernandes*, \",\"doi\":\"10.1021/acs.jmedchem.4c0180610.1021/acs.jmedchem.4c01806\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Cu(II) complexes with 2,2′:6′,2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl<sub>2</sub>(L<sup><i>n</i></sup>)]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes (<b>Cu1a</b> and <b>Cu1b</b>) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. <b>Cu1a</b> and <b>Cu1b</b> do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).</p>\",\"PeriodicalId\":46,\"journal\":{\"name\":\"Journal of Medicinal Chemistry\",\"volume\":\"67 21\",\"pages\":\"19475–19502 19475–19502\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/epdf/10.1021/acs.jmedchem.4c01806\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01806\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01806","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Optimization of Antiproliferative Properties of Triimine Copper(II) Complexes
Cu(II) complexes with 2,2′:6′,2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl2(Ln)]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes (Cu1a and Cu1b) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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