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具有肽键的新型有机锡(IV)羧酸盐:合成、结构解析、物理化学表征及药理学研究

Newly designed organotin(IV) carboxylates with peptide linkage: Synthesis, structural elucidation, physicochemical characterizations and pharmacological investigations.

作者信息

Sirajuddin Muhammad, McKee Vickie, Tariq Muhammad, Ali Saqib

机构信息

Department of Chemistry, University of Science & Technology, Bannu, 28100, Pakistan.

Department of Chemistry, Dublin City University, Ireland, UK.

出版信息

Eur J Med Chem. 2018 Jan 1;143:1903-1918. doi: 10.1016/j.ejmech.2017.11.001. Epub 2017 Nov 4.

Abstract

Fourteen new organotin(IV) carboxylate complexes with peptide linkage of (2-(4-methoxy-2-nitrophenylcarbamoyl)benzoic acid) were successfully synthesized and characterized by elemental analyses, FT-IR, NMR (H, C and Sn) and single crystal X-ray techniques. FT-IR results of the sodium salt of 2-(4-methoxy-2-nitrophenylcarbamoyl)benzoic acid and complexes showed that the coordination took place via oxygen atoms of the carboxylate group. J(Sn-C), J(Sn-H) and θ values calculated from H and C NMR data using Lockhart's equation reveal a trigonal bipyramidal geometry for triorganotin(IV) derivatives and an octahedral geometry for diorganotin(IV) derivatives. Crystallographic data for three triorganotin(IV) complexes (1-3) showed the tin has distorted trigonal bipyramidal geometry. In vitro anticancer activity against lung carcinoma (H-157) and kidney fibroblast (BHK-21) cell lines as well as antileishmanial activity against the promastigote forms of leishmania major of the synthesized compounds were also studied and the complexes were found biologically active. The in vitro antibacterial activity of most of the synthesized organotin(IV) derivatives against the studied bacterial pathogens is higher than those of the standard 3rd generation antibiotics such as Tetracycline, Penicillin G, Ampicillin, Amoxicillin. This suggest the use of these newly designed organotin(IV) derivatives as potent antibiotics. The synthesized compounds interact with DNA via intercalative mode of interaction. Viscosity measurement results also support the intercalative mode of interaction for the compounds with DNA.

摘要

成功合成了十四种具有(2-(4-甲氧基-2-硝基苯基氨基甲酰基)苯甲酸)肽键的新型有机锡(IV)羧酸盐配合物,并通过元素分析、傅里叶变换红外光谱(FT-IR)、核磁共振(H、C和Sn)以及单晶X射线技术对其进行了表征。2-(4-甲氧基-2-硝基苯基氨基甲酰基)苯甲酸及其配合物的钠盐的FT-IR结果表明,配位是通过羧酸盐基团的氧原子进行的。使用洛克哈特方程从H和C NMR数据计算得到的J(Sn-C)、J(Sn-H)和θ值表明,三有机锡(IV)衍生物具有三角双锥几何构型,二有机锡(IV)衍生物具有八面体几何构型。三种三有机锡(IV)配合物(1-3)的晶体学数据表明,锡具有扭曲的三角双锥几何构型。还研究了合成化合物对肺癌(H-157)和肾成纤维细胞(BHK-21)细胞系的体外抗癌活性以及对杜氏利什曼原虫前鞭毛体形式的抗利什曼活性,发现这些配合物具有生物活性。大多数合成的有机锡(IV)衍生物对所研究的细菌病原体的体外抗菌活性高于四环素、青霉素G、氨苄青霉素、阿莫西林等标准第三代抗生素。这表明这些新设计的有机锡(IV)衍生物可作为有效的抗生素使用。合成的化合物通过插入相互作用模式与DNA相互作用。粘度测量结果也支持这些化合物与DNA的插入相互作用模式。

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