New (3-(1H-benzo[d]imidazol-2-yl))/(3-(3H-imidazo[4,5-b]pyridin-2-yl))-(1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates as tubulin polymerization inhibitors†,RSC Medicinal Chemistry

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New (3-(1H-benzo[d]imidazol-2-yl))/(3-(3H-imidazo[4,5-b]pyridin-2-yl))-(1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates as tubulin polymerization inhibitors†
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-12-12 00:00:00 , DOI: 10.1039/c7md00450h
Kishore Mullagiri ₁ , V Lakshma Nayak ₁ , Satish Sunkari ₁ , Geeta Sai Mani ₂ , Sravanthi Devi Guggilapu ₂ , Burri Nagaraju ₁ , Abdullah Alarifi ₃ , Ahmed Kamal _{1,

2,

3}

Affiliation

A series of new (3-(1H-benzo[d]imidazol-2-yl))/(3-(3H-imidazo[4,5-b]pyridin-2-yl))-(1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates 4–6(a–i) were synthesized and evaluated for their antiproliferative activity on selected human cancer cell lines such as prostate (DU-145), lung (A549), cervical (HeLa) and breast (MCF-7). Most of these conjugates showed considerable cytotoxicity with IC₅₀ values ranging from 0.54 to 31.86 μM. Among them, compounds 5g and 6f showed significant activity against human prostate cancer cell line DU-145 with IC₅₀ values of 0.68 μM and 0.54 μM, respectively. Tubulin polymerization assay and immunofluorescence analysis results suggest that these compounds effectively inhibit microtubule assembly formation in DU-145. Further, the apoptosis-inducing ability of these derivatives (5g and 6f) was confirmed by Hoechst staining, measurement of mitochondrial membrane potential and ROS generation and annexin V-FITC assays.

中文翻译：

新的(3-(1H-苯并[d]咪唑-2-基))/(3-(3H-咪唑[4,5-b]吡啶-2-基))-(1H-吲哚-5-基) (3,4,5-三甲氧基苯基)甲酮缀合物作为微管蛋白聚合抑制剂†

一系列新的(3-( 1H-苯并[ d ]咪唑-2-基))/(3-( 3H-咪唑[4,5 - b ]吡啶-2-基))- ( 1H- indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates 4-6(a-i)被合成并评估它们对选定的人类癌细胞系如前列腺 (DU-145)、肺 ( A549)、宫颈 (HeLa) 和乳房 (MCF-7)。大多数这些缀合物显示出相当大的细胞毒性，IC ₅₀值范围为 0.54 至 31.86 μM。其中，化合物5g和6f对人前列腺癌细胞系 DU-145 显示出显着的活性，IC ₅₀值分别为 0.68 μM 和 0.54 μM。微管蛋白聚合测定和免疫荧光分析结果表明，这些化合物可有效抑制 DU-145 中微管组装的形成。此外，这些衍生物（ 5g和6f ）的细胞凋亡诱导能力通过 Hoechst 染色、线粒体膜电位和 ROS 生成的测量以及膜联蛋白 V-FITC 测定得到证实。

更新日期：2017-12-12

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