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硒-N-杂环卡宾化合物的绿色合成:抗菌和抗癌潜力评价。

Green synthesis of selenium-N-heterocyclic carbene compounds: Evaluation of antimicrobial and anticancer potential.

机构信息

Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan.

Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Pulau Penang, Malaysia.

出版信息

Bioorg Chem. 2019 Sep;90:103042. doi: 10.1016/j.bioorg.2019.103042. Epub 2019 Jun 7.

Abstract

Three benzimidazolium salts (III-V) and respective selenium adducts (VI-VIII) were designed, synthesized and characterized by various analytical techniques (FT-IR and NMR H, C). Selected salts and respective selenium N-Heterocyclic carbenes (selenium-NHC) adducts were tested in vitro against Cervical Cancer Cell line (Hela), Breast Adenocarcinoma cell line (MCF-7), Retinal Ganglion Cell line (RGC-5) and Mouse Melanoma Cell line (B16F10) using MTT assay and the results were compared with standard drug 5-Fluorouracil. Se-NHC compounds and azolium salts showed significant anticancer potential. Molecular docking studies of compounds (VI, VII and VIII) showed strong binding energies and ligand affinity toward following angiogenic factors: VEGF-A (vascular endothelial growth factor A), EGF (human epidermal growth factor), HIF (Hypoxia-inducible factor) and COX-1 (Cyclooxygenase-1) suggesting that the anticancer activity of adducts (VI, VII and VIII) may be due to their strong anti-angiogenic effect. In addition, compounds III-VIII were screened for their antibacterial and antifungal potential. Adduct VI was found to be potent anti-fungal agent against A. Niger with zone of inhibition (ZI) value 27.01 ± 0.251 mm which is better than standard drug Clotrimazole tested in parallel.

摘要

三种苯并咪唑盐(III-V)及其相应的硒加合物(VI-VIII)被设计、合成并通过各种分析技术(FT-IR 和 NMR H、C)进行了表征。选择的盐及其相应的硒 N-杂环卡宾(硒-NHC)加合物在体外使用 MTT 测定法针对宫颈癌细胞系(Hela)、乳腺癌腺癌细胞系(MCF-7)、视网膜神经节细胞系(RGC-5)和小鼠黑色素瘤细胞系(B16F10)进行了测试,并将结果与标准药物 5-氟尿嘧啶进行了比较。Se-NHC 化合物和azolium 盐表现出显著的抗癌潜力。化合物(VI、VII 和 VIII)的分子对接研究表明,它们对以下血管生成因子具有很强的结合能和配体亲和力:VEGF-A(血管内皮生长因子 A)、EGF(人表皮生长因子)、HIF(缺氧诱导因子)和 COX-1(环氧化酶-1),表明加合物(VI、VII 和 VIII)的抗癌活性可能是由于它们具有很强的抗血管生成作用。此外,还对化合物 III-VIII 进行了抗菌和抗真菌潜力的筛选。加合物 VI 被发现是一种对抗 A. Niger 的有效抗真菌剂,其抑菌环(ZI)值为 27.01±0.251mm,优于平行测试的标准药物克霉唑。

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