Tayná Saraiva de Lavor , Maria Henriqueta Silvestre Teixeira , Patrícia Alves de Matos , Ricardo Campos Lino , Clara Maria Faria Silva , Marcos Eduardo Gomes do Carmo , Marcelo Emílio Beletti , Antonio Otavio T. Patrocinio , Robson José de Oliveira Júnior , Tayana Mazin Tsubone
{"title":"生物分子相互作用对铼(I)三羰基复合物细胞毒性效应的影响。","authors":"Tayná Saraiva de Lavor , Maria Henriqueta Silvestre Teixeira , Patrícia Alves de Matos , Ricardo Campos Lino , Clara Maria Faria Silva , Marcos Eduardo Gomes do Carmo , Marcelo Emílio Beletti , Antonio Otavio T. Patrocinio , Robson José de Oliveira Júnior , Tayana Mazin Tsubone","doi":"10.1016/j.jinorgbio.2024.112600","DOIUrl":null,"url":null,"abstract":"<div><p>Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)<sub>3</sub>(NN)(py)<sup>+</sup> core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes <em>fac-</em>[Re(CO)<sub>3</sub>(NN)(py)]<sup>+</sup>, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) or dipyrido[3,2-a:2′3’-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that <em>fac-</em>[Re(CO)<sub>3</sub>(dppz)(py)]<sup>+</sup> has higher Log P<sub>o/w</sub> and binding constant (K<sub>b</sub>) with biomolecules (protein, lipid and DNA) compared to complexes of <em>fac-</em>[Re(CO)<sub>3</sub>(phen)(py)]<sup>+</sup> and <em>fac-</em>[Re(CO)<sub>3</sub>(dpq)(py)]<sup>+</sup>. As consequence, <em>fac-</em>[Re(CO)<sub>3</sub>(dppz)(py)]<sup>+</sup> exhibited the highest cytotoxicity (IC<sub>50</sub> = 8.5 μM for HeLa cells) for <em>fac-</em>[Re(CO)<sub>3</sub>(dppz)(py)]<sup>+</sup> among the studied compounds (IC<sub>50</sub> > 15 μM). This highest cytotoxicity of <em>fac-</em>[Re(CO)<sub>3</sub>(dppz)(py)]<sup>+</sup> are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"257 ","pages":"Article 112600"},"PeriodicalIF":3.8000,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The impact of biomolecule interactions on the cytotoxic effects of rhenium(I) tricarbonyl complexes\",\"authors\":\"Tayná Saraiva de Lavor , Maria Henriqueta Silvestre Teixeira , Patrícia Alves de Matos , Ricardo Campos Lino , Clara Maria Faria Silva , Marcos Eduardo Gomes do Carmo , Marcelo Emílio Beletti , Antonio Otavio T. Patrocinio , Robson José de Oliveira Júnior , Tayana Mazin Tsubone\",\"doi\":\"10.1016/j.jinorgbio.2024.112600\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)<sub>3</sub>(NN)(py)<sup>+</sup> core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes <em>fac-</em>[Re(CO)<sub>3</sub>(NN)(py)]<sup>+</sup>, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) or dipyrido[3,2-a:2′3’-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that <em>fac-</em>[Re(CO)<sub>3</sub>(dppz)(py)]<sup>+</sup> has higher Log P<sub>o/w</sub> and binding constant (K<sub>b</sub>) with biomolecules (protein, lipid and DNA) compared to complexes of <em>fac-</em>[Re(CO)<sub>3</sub>(phen)(py)]<sup>+</sup> and <em>fac-</em>[Re(CO)<sub>3</sub>(dpq)(py)]<sup>+</sup>. As consequence, <em>fac-</em>[Re(CO)<sub>3</sub>(dppz)(py)]<sup>+</sup> exhibited the highest cytotoxicity (IC<sub>50</sub> = 8.5 μM for HeLa cells) for <em>fac-</em>[Re(CO)<sub>3</sub>(dppz)(py)]<sup>+</sup> among the studied compounds (IC<sub>50</sub> > 15 μM). This highest cytotoxicity of <em>fac-</em>[Re(CO)<sub>3</sub>(dppz)(py)]<sup>+</sup> are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).</p></div>\",\"PeriodicalId\":364,\"journal\":{\"name\":\"Journal of Inorganic Biochemistry\",\"volume\":\"257 \",\"pages\":\"Article 112600\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-05-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inorganic Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0162013424001235\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inorganic Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0162013424001235","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The impact of biomolecule interactions on the cytotoxic effects of rhenium(I) tricarbonyl complexes
Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)3(NN)(py)+ core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes fac-[Re(CO)3(NN)(py)]+, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) or dipyrido[3,2-a:2′3’-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that fac-[Re(CO)3(dppz)(py)]+ has higher Log Po/w and binding constant (Kb) with biomolecules (protein, lipid and DNA) compared to complexes of fac-[Re(CO)3(phen)(py)]+ and fac-[Re(CO)3(dpq)(py)]+. As consequence, fac-[Re(CO)3(dppz)(py)]+ exhibited the highest cytotoxicity (IC50 = 8.5 μM for HeLa cells) for fac-[Re(CO)3(dppz)(py)]+ among the studied compounds (IC50 > 15 μM). This highest cytotoxicity of fac-[Re(CO)3(dppz)(py)]+ are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).
期刊介绍:
The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.