New Organotin (IV) Compounds Derived from Dehydroacetic Acid and Thiosemicarbazides: Synthesis, Rational Design, Cytotoxic Evaluation, and Molecular Docking Simulation.

IF 4.7 3区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bioinorganic Chemistry and Applications Pub Date : 2023-10-25 eCollection Date: 2023-01-01 DOI:10.1155/2023/7901843
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
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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.

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脱氢乙酸和缩氨基硫脲衍生的新型有机锡(IV)化合物:合成、合理设计、细胞毒性评价和分子对接模拟。
有机锡配合物是通过与三种组分的一锅反应制备的,其中氨基硫脲或4-甲基-3-氨基硫脲或-4-苯基氨基硫脲、脱氢乙酸(DHA)与二丁基、二苯基、二环己基和双[(三甲基甲硅烷基)甲基]锡(IV)氧化物反应;通过红外光谱、紫外-可见光谱、质谱和核磁共振对所有配合物进行了表征。119Sn NMR揭示了对应于溶液中五配位环境的化学位移。这两种配合物的X射线晶体学证明,通过配体的三个给体原子、硫醇的硫、亚胺基的氮和吡喃环的氧,在锡周围形成了具有五配位几何结构的单体配合物。五个配位的配合物3a(Bu2SnL3)、3c(Ph2SnO3)和3d(Cy2SnL3。磺基罗丹明B测定评估了有机锡(IV)复合物对MDA-MB-231和MCF-7(人乳腺癌)细胞系以及一种正常COS-7(非洲绿猴肾成纤维细胞)的细胞毒性。IC50值证明了对癌症细胞的显著抗增殖作用;该配合物比顺铂阳性对照和相应的配体脱氢乙酸缩氨基硫脲(L1)、脱氢乙酸-N(4)-甲基缩氨基脲(L2)和脱氢乙酸-N。IC50值还表明,与MCF-7相比,有机锡(IV)复合物对三阴性乳腺细胞系MDA-MB-231的细胞毒性更强,诱导了显著的形态学改变。有机锡(IV)1c(Ph2SnL1)、1d(Cy2SnL1和1e((CH3)3SiCH2)2SnL1的相互作用用ss-DNA通过荧光进行评估;荧光强度的变化表明溴化乙锭(EB)的位移,证实了有机锡(IV)复合物与ss-DNA的相互作用;结果显示出DNA结合亲和力。通过等温滴定量热法获得的热力学参数表明,1c(Ph2SnL1)与ss-ADN的相互作用是放热的。分子对接研究还表明,有机锡(IV)复合物通过常规氢键、碳-氢键和π-烷基相互作用嵌入DNA。这些复合物进一步显示出比顺铂更大的对DNA的亲和力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioinorganic Chemistry and Applications
Bioinorganic Chemistry and Applications 化学-生化与分子生物学
CiteScore
7.00
自引率
5.30%
发文量
105
审稿时长
>12 weeks
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.
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