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N-炔丙基异吲哚酮-曼尼希单加合物和双加合物:合成及其对胎儿三毛滴虫体外活性的初步分析

N-Propargylated isatin-Mannich mono- and bis-adducts: synthesis and preliminary analysis of in vitro activity against Tritrichomonas foetus.

作者信息

Kumar Kewal, Bhargava Gaurav, Land Kirkwood M, Chang Kai-Hsiang, Arora Reena, Sen Somdutta, Kumar Vipan

机构信息

Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.

Department of Applied Sciences, Punjab Technical University, Kapurthala 144601, India.

出版信息

Eur J Med Chem. 2014 Mar 3;74:657-63. doi: 10.1016/j.ejmech.2014.01.015. Epub 2014 Jan 18.

Abstract

Cu(I)Cl promoted synthesis of N-propargylated-isatin Mannich mono- and bis-adducts with an extension towards the synthesis of N-propargylated-isatin-7-chloroquinoline conjugates was described. The synthesized scaffolds were evaluated for their in vitro activity against the veterinary protozoal pathogen Tritrichomonas foetus and cytotoxicity against human prostate (PC-3) cancer cell line. The preliminary evaluation data revealed the enhancement in the activity profiles with the introduction of 7-chloroquinoline ring with the most active conjugates 7a, 7c and 7d exhibiting an IC₅₀ of 22.2, 11.3 and 24.5 μM respectively against T. foetus and minimal toxicity against human prostate (PC-3) cell lines.

摘要

描述了Cu(I)Cl促进的N-炔丙基异吲哚酮曼尼希单加合物和双加合物的合成,并将其扩展至N-炔丙基异吲哚酮-7-氯喹啉共轭物的合成。对合成的支架进行了体外抗兽医原生动物病原体胎儿三毛滴虫活性以及对人前列腺(PC-3)癌细胞系细胞毒性的评估。初步评估数据显示,引入7-氯喹啉环后活性有所增强,最具活性的共轭物7a、7c和7d对胎儿三毛滴虫的IC₅₀分别为22.2、11.3和24.5 μM,对人前列腺(PC-3)细胞系的毒性最小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d28/7115568/e530bda9adb4/fx1.jpg

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