Alexandre B. de Carvalho, Ana M. S. Souza, Larissa Pereira Bento, Mariana de Oliveira Silva, Elaine M. Souza-Fagundes, Renata Diniz, Heloisa Beraldo
{"title":"铟（III）与拉帕酚的配合物：对人类乳腺肿瘤细胞的细胞毒性作用以及与 DNA 的相互作用。","authors":"Alexandre B. de Carvalho, Ana M. S. Souza, Larissa Pereira Bento, Mariana de Oliveira Silva, Elaine M. Souza-Fagundes, Renata Diniz, Heloisa Beraldo","doi":"10.1007/s00775-024-02062-0","DOIUrl":null,"url":null,"abstract":"<div><p>Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl<sub>2</sub>].4H<sub>2</sub>O (<b>1</b>), [In(lap)<sub>2</sub>Cl(Et<sub>3</sub>N)] (<b>2</b>), [In(lap)<sub>3</sub>]·2H<sub>2</sub>O (<b>3</b>) [In(lap)(bipy)Cl<sub>2</sub>] bipy = 2,2′-bipyridine (<b>4</b>) and [In(lap)(phen)Cl<sub>2</sub>] phen = 1,10-phenanthroline (<b>5</b>) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (<b>4</b>) and (<b>5</b>) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2′-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (<b>4</b>) and (<b>5</b>) interacted with CT-DNA in vitro by an intercalative mode, only <b>5</b> exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (<b>5</b>) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (<b>5</b>) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (<b>5</b>) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (<b>5</b>) are of utmost relevance.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"29 5","pages":"519 - 529"},"PeriodicalIF":2.7000,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Indium(III) complexes with lapachol: cytotoxic effects against human breast tumor cells and interactions with DNA\",\"authors\":\"Alexandre B. de Carvalho, Ana M. S. Souza, Larissa Pereira Bento, Mariana de Oliveira Silva, Elaine M. Souza-Fagundes, Renata Diniz, Heloisa Beraldo\",\"doi\":\"10.1007/s00775-024-02062-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl<sub>2</sub>].4H<sub>2</sub>O (<b>1</b>), [In(lap)<sub>2</sub>Cl(Et<sub>3</sub>N)] (<b>2</b>), [In(lap)<sub>3</sub>]·2H<sub>2</sub>O (<b>3</b>) [In(lap)(bipy)Cl<sub>2</sub>] bipy = 2,2′-bipyridine (<b>4</b>) and [In(lap)(phen)Cl<sub>2</sub>] phen = 1,10-phenanthroline (<b>5</b>) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (<b>4</b>) and (<b>5</b>) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2′-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (<b>4</b>) and (<b>5</b>) interacted with CT-DNA in vitro by an intercalative mode, only <b>5</b> exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (<b>5</b>) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (<b>5</b>) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (<b>5</b>) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. 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Indium(III) complexes with lapachol: cytotoxic effects against human breast tumor cells and interactions with DNA
Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl2].4H2O (1), [In(lap)2Cl(Et3N)] (2), [In(lap)3]·2H2O (3) [In(lap)(bipy)Cl2] bipy = 2,2′-bipyridine (4) and [In(lap)(phen)Cl2] phen = 1,10-phenanthroline (5) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (4) and (5) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2′-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (4) and (5) interacted with CT-DNA in vitro by an intercalative mode, only 5 exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (5) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (5) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (5) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (5) are of utmost relevance.
期刊介绍：
Biological inorganic chemistry is a growing field of science that embraces the principles of biology and inorganic chemistry and impacts other fields ranging from medicine to the environment. JBIC (Journal of Biological Inorganic Chemistry) seeks to promote this field internationally. The Journal is primarily concerned with advances in understanding the role of metal ions within a biological matrix—be it a protein, DNA/RNA, or a cell, as well as appropriate model studies. Manuscripts describing high-quality original research on the above topics in English are invited for submission to this Journal. The Journal publishes original articles, minireviews, and commentaries on debated issues.
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