New Organotin (IV) Compounds Derived from Dehydroacetic Acid and Thiosemicarbazides: Synthesis, Rational Design, Cytotoxic Evaluation, and Molecular Docking Simulation.
Elizabeth Gómez, José Miguel Galván-Hidalgo, Guillermo Pérez-Cuéllar, Karoline Alondra Huerta-Landa, Arturo González-Hernández, Omar Gómez-García, Dulce Andrade-Pavón, Teresa Ramírez-Apan, Karla Daniela Rodríguez Hernández, Simón Hernández, Patricia Cano-Sánchez, Homero Gómez-Velasco
{"title":"New Organotin (IV) Compounds Derived from Dehydroacetic Acid and Thiosemicarbazides: Synthesis, Rational Design, Cytotoxic Evaluation, and Molecular Docking Simulation.","authors":"Elizabeth Gómez, José Miguel Galván-Hidalgo, Guillermo Pérez-Cuéllar, Karoline Alondra Huerta-Landa, Arturo González-Hernández, Omar Gómez-García, Dulce Andrade-Pavón, Teresa Ramírez-Apan, Karla Daniela Rodríguez Hernández, Simón Hernández, Patricia Cano-Sánchez, Homero Gómez-Velasco","doi":"10.1155/2023/7901843","DOIUrl":null,"url":null,"abstract":"<p><p>Organotin complexes were prepared through a one-pot reaction with three components by reacting thiosemicarbazide or 4-methyl-3-thiosemicarbazide or 4-phenylthiosemicarbazide, dehydroacetic acid (DHA) and dibutyl, diphenyl, dicyclohexyl, and bis[(trimethylsilyl)methyl]tin(IV) oxides; all complexes were characterized by infrared (IR), ultraviolet-visible (UV-vis), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. The <sup>119</sup>Sn NMR revealed chemical shifts corresponding to a pentacoordinated environment in solution. The X-ray crystallography of the two complexes evidenced the formation of monomeric complexes with a pentacoordinated geometry around tin via three donor atoms from the ligand, the sulfur of the thiol, the nitrogen of the imine group, and the oxygen of the pyran ring. The geometries of the five-coordinated complexes <b>3a</b> (Bu<sub>2</sub>SnL3), <b>3c</b> (Ph<sub>2</sub>SnL3), and <b>3d</b> (Cy<sub>2</sub>SnL3) acid were intermediate between square pyramidal and trigonal bipyramidal, and complex <b>1a</b> (Bu<sub>2</sub>SnL1) adopted a bipyramidal trigonal geometry (BPT). The sulforhodamine B assay assessed the cytotoxicity of organotin(IV) complexes against the MDA-MB-231 and MCF-7 (human mammary adenocarcinoma) cell lines and one normal COS-7 (African green monkey kidney fibroblast). The IC<sub>50</sub> values evidenced a significant antiproliferative effect on cancer cells; the complexes were more potent than the positive cisplatin control and the corresponding ligands, dehydroacetic acid thiosemicarbazone (<b>L1</b>), dehydroacetic acid-N(4)-methylthiosemicarbazone (<b>L2</b>), and dehydroacetic acid-N(4)-phenylthiosemicarbazone (<b>L3</b>). The IC<sub>50</sub> values also indicated that the organotin(IV) complexes were more cytotoxic against the triple-negative breast cell line MDA-MB-231 than MCF-7, inducing significant morphological alterations. The interactions of organotin(IV) <b>1c</b> (Ph<sub>2</sub>SnL1), <b>1d</b> (Cy<sub>2</sub>SnL1), and <b>1e</b> (((CH<sub>3</sub>)<sub>3</sub>SiCH<sub>2</sub>)<sub>2</sub>SnL1) were evaluated with ss-DNA by fluorescence; intensity changes of the fluorescence were indicative of the displacement of ethidium bromide (EB), confirming the interaction of the organotin(IV) complexes with ss-DNA; the results showed a DNA binding affinity. The thermodynamic parameters obtained through isothermal titration calorimetry showed that the interaction of <b>1c</b> (Ph<sub>2</sub>SnL1), with ss-ADN, was exothermic. Molecular docking studies also demonstrated that the organotin(IV) complexes were intercalated in DNA by conventional hydrogen bonds, carbon-hydrogen bonds, and <i>π</i>-alkyl interactions. These complexes furthermore showed a greater affinity towards DNA than cisplatin.</p>","PeriodicalId":8914,"journal":{"name":"Bioinorganic Chemistry and Applications","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620030/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioinorganic Chemistry and Applications","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1155/2023/7901843","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Organotin complexes were prepared through a one-pot reaction with three components by reacting thiosemicarbazide or 4-methyl-3-thiosemicarbazide or 4-phenylthiosemicarbazide, dehydroacetic acid (DHA) and dibutyl, diphenyl, dicyclohexyl, and bis[(trimethylsilyl)methyl]tin(IV) oxides; all complexes were characterized by infrared (IR), ultraviolet-visible (UV-vis), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. The 119Sn NMR revealed chemical shifts corresponding to a pentacoordinated environment in solution. The X-ray crystallography of the two complexes evidenced the formation of monomeric complexes with a pentacoordinated geometry around tin via three donor atoms from the ligand, the sulfur of the thiol, the nitrogen of the imine group, and the oxygen of the pyran ring. The geometries of the five-coordinated complexes 3a (Bu2SnL3), 3c (Ph2SnL3), and 3d (Cy2SnL3) acid were intermediate between square pyramidal and trigonal bipyramidal, and complex 1a (Bu2SnL1) adopted a bipyramidal trigonal geometry (BPT). The sulforhodamine B assay assessed the cytotoxicity of organotin(IV) complexes against the MDA-MB-231 and MCF-7 (human mammary adenocarcinoma) cell lines and one normal COS-7 (African green monkey kidney fibroblast). The IC50 values evidenced a significant antiproliferative effect on cancer cells; the complexes were more potent than the positive cisplatin control and the corresponding ligands, dehydroacetic acid thiosemicarbazone (L1), dehydroacetic acid-N(4)-methylthiosemicarbazone (L2), and dehydroacetic acid-N(4)-phenylthiosemicarbazone (L3). The IC50 values also indicated that the organotin(IV) complexes were more cytotoxic against the triple-negative breast cell line MDA-MB-231 than MCF-7, inducing significant morphological alterations. The interactions of organotin(IV) 1c (Ph2SnL1), 1d (Cy2SnL1), and 1e (((CH3)3SiCH2)2SnL1) were evaluated with ss-DNA by fluorescence; intensity changes of the fluorescence were indicative of the displacement of ethidium bromide (EB), confirming the interaction of the organotin(IV) complexes with ss-DNA; the results showed a DNA binding affinity. The thermodynamic parameters obtained through isothermal titration calorimetry showed that the interaction of 1c (Ph2SnL1), with ss-ADN, was exothermic. Molecular docking studies also demonstrated that the organotin(IV) complexes were intercalated in DNA by conventional hydrogen bonds, carbon-hydrogen bonds, and π-alkyl interactions. These complexes furthermore showed a greater affinity towards DNA than cisplatin.
期刊介绍:
Bioinorganic Chemistry and Applications is primarily devoted to original research papers, but also publishes review articles, editorials, and letter to the editor in the general field of bioinorganic chemistry and its applications. Its scope includes all aspects of bioinorganic chemistry, including bioorganometallic chemistry and applied bioinorganic chemistry. The journal welcomes papers relating to metalloenzymes and model compounds, metal-based drugs, biomaterials, biocatalysis and bioelectronics, metals in biology and medicine, metals toxicology and metals in the environment, metal interactions with biomolecules and spectroscopic applications.