{"title":"基于希夫碱的新型铂(II)配合物:合成、规范、x射线结构、ADMET、DFT、分子对接、抗乳腺癌活性","authors":"Mahboube Eslami Moghadam, Maryam Hasanzadeh Esfahani, Mahdi Behzad, Samaneh Zolghadri, Nadali Ramezani, Yasaman Azadi","doi":"10.1007/s00775-023-02005-1","DOIUrl":null,"url":null,"abstract":"<div><p>Acylpyrazolone-based Schiff base ligands (HL<sup><i>n</i></sup>) and their corresponding Pt(II) complexes with the general formula [Pt(L<sup><i>n</i></sup>)(Cl)] (<i>n</i>?=?1–3)?were synthesized and characterized by different spectroscopic techniques including <sup>1</sup>H-NMR, <sup>195</sup>Pt-NMR, LC-Mass, FT–IR, and UV–Vis spectroscopy, as well as elemental analysis. The crystal structure of one of the Schiff base ligands was also obtained. Based on the ADMET comparative results and the bioavailability radar charts, the complexes are completely drug-like. The Schiff base complexes with a structural difference of one methyl group in ligand were used as anticancer agents against human breast cancer cell lines SKBR3 and MDA-MB-231. The IC<sub>50</sub> values after treatment by [Pt(L<sup>1</sup>)Cl] and [Pt(L<sup>2</sup>)Cl] were obtained more than cisplatin and less than carboplatin on cancer cells MDA-MB-231 and SKBR3, while the IC<sub>50</sub> value of [Pt(L<sup>3</sup>)Cl] was more than both other complexes and clinical Pt drugs. Molecular docking data showed that the groove binding is the main interaction with DNA double strands with a minor contribution from electrostatic interactions. To investigate the structure–activity relationship, DFT computational was done. All quantum chemical parameters display the drug approaching biomacromolecule and more biological activity of [Pt(L<sup>1</sup>)Cl]?>?[Pt(L<sup>2</sup>)Cl]?>?[Pt(L<sup>3</sup>)Cl]. So, three Schiff base platinum complexes can be suitable candidates as anticancer drugs.</p><h3>Graphical abstract</h3>\n <figure><div><div><div><picture><source><img></source></picture></div><div><p>Schiff-base ligands (HLn) and their Pt(II) complexes ([Pt(Ln)(Cl)], n=1-3) were obtained. To investigate their biological property and main interactions with DNA, ADMET, and cytotoxicity against MDA-MB-231 and SKBR3, DFT, and Molecular docking were done.</p></div></div></div></figure>\n </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 5","pages":"519 - 529"},"PeriodicalIF":2.7000,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-023-02005-1.pdf","citationCount":"2","resultStr":"{\"title\":\"New platinum (II) complexes based on schiff bases: synthesis, specification, X-ray structure, ADMET, DFT, molecular docking, and anticancer activity against breast cancer\",\"authors\":\"Mahboube Eslami Moghadam, Maryam Hasanzadeh Esfahani, Mahdi Behzad, Samaneh Zolghadri, Nadali Ramezani, Yasaman Azadi\",\"doi\":\"10.1007/s00775-023-02005-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Acylpyrazolone-based Schiff base ligands (HL<sup><i>n</i></sup>) and their corresponding Pt(II) complexes with the general formula [Pt(L<sup><i>n</i></sup>)(Cl)] (<i>n</i>?=?1–3)?were synthesized and characterized by different spectroscopic techniques including <sup>1</sup>H-NMR, <sup>195</sup>Pt-NMR, LC-Mass, FT–IR, and UV–Vis spectroscopy, as well as elemental analysis. The crystal structure of one of the Schiff base ligands was also obtained. Based on the ADMET comparative results and the bioavailability radar charts, the complexes are completely drug-like. The Schiff base complexes with a structural difference of one methyl group in ligand were used as anticancer agents against human breast cancer cell lines SKBR3 and MDA-MB-231. The IC<sub>50</sub> values after treatment by [Pt(L<sup>1</sup>)Cl] and [Pt(L<sup>2</sup>)Cl] were obtained more than cisplatin and less than carboplatin on cancer cells MDA-MB-231 and SKBR3, while the IC<sub>50</sub> value of [Pt(L<sup>3</sup>)Cl] was more than both other complexes and clinical Pt drugs. Molecular docking data showed that the groove binding is the main interaction with DNA double strands with a minor contribution from electrostatic interactions. To investigate the structure–activity relationship, DFT computational was done. All quantum chemical parameters display the drug approaching biomacromolecule and more biological activity of [Pt(L<sup>1</sup>)Cl]?>?[Pt(L<sup>2</sup>)Cl]?>?[Pt(L<sup>3</sup>)Cl]. So, three Schiff base platinum complexes can be suitable candidates as anticancer drugs.</p><h3>Graphical abstract</h3>\\n <figure><div><div><div><picture><source><img></source></picture></div><div><p>Schiff-base ligands (HLn) and their Pt(II) complexes ([Pt(Ln)(Cl)], n=1-3) were obtained. To investigate their biological property and main interactions with DNA, ADMET, and cytotoxicity against MDA-MB-231 and SKBR3, DFT, and Molecular docking were done.</p></div></div></div></figure>\\n </div>\",\"PeriodicalId\":603,\"journal\":{\"name\":\"JBIC Journal of Biological Inorganic Chemistry\",\"volume\":\"28 5\",\"pages\":\"519 - 529\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-07-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s00775-023-02005-1.pdf\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JBIC Journal of Biological Inorganic Chemistry\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00775-023-02005-1\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JBIC Journal of Biological Inorganic Chemistry","FirstCategoryId":"1","ListUrlMain":"https://link.springer.com/article/10.1007/s00775-023-02005-1","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
New platinum (II) complexes based on schiff bases: synthesis, specification, X-ray structure, ADMET, DFT, molecular docking, and anticancer activity against breast cancer
Acylpyrazolone-based Schiff base ligands (HLn) and their corresponding Pt(II) complexes with the general formula [Pt(Ln)(Cl)] (n?=?1–3)?were synthesized and characterized by different spectroscopic techniques including 1H-NMR, 195Pt-NMR, LC-Mass, FT–IR, and UV–Vis spectroscopy, as well as elemental analysis. The crystal structure of one of the Schiff base ligands was also obtained. Based on the ADMET comparative results and the bioavailability radar charts, the complexes are completely drug-like. The Schiff base complexes with a structural difference of one methyl group in ligand were used as anticancer agents against human breast cancer cell lines SKBR3 and MDA-MB-231. The IC50 values after treatment by [Pt(L1)Cl] and [Pt(L2)Cl] were obtained more than cisplatin and less than carboplatin on cancer cells MDA-MB-231 and SKBR3, while the IC50 value of [Pt(L3)Cl] was more than both other complexes and clinical Pt drugs. Molecular docking data showed that the groove binding is the main interaction with DNA double strands with a minor contribution from electrostatic interactions. To investigate the structure–activity relationship, DFT computational was done. All quantum chemical parameters display the drug approaching biomacromolecule and more biological activity of [Pt(L1)Cl]?>?[Pt(L2)Cl]?>?[Pt(L3)Cl]. So, three Schiff base platinum complexes can be suitable candidates as anticancer drugs.
Graphical abstract
Schiff-base ligands (HLn) and their Pt(II) complexes ([Pt(Ln)(Cl)], n=1-3) were obtained. To investigate their biological property and main interactions with DNA, ADMET, and cytotoxicity against MDA-MB-231 and SKBR3, DFT, and Molecular docking were done.
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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