Journal of medicinal and pharmaceutical chemistry 2009-10-08

Discovery of novel antileishmanial agents in an attempt to synthesize pentamidine-aplysinopsin hybrid molecule.

Sharad Porwal, Shikha S Chauhan, Prem M S Chauhan, Nishi Shakya, Aditya Verma, Suman Gupta

文献索引：J. Med. Chem. 52 , 5793-802, (2009)

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摘要

In an attempt to synthesize pentamidine-aplysinopsin hybrid molecule 25, a lead molecule 8 (containing Z-configured aplysinopsin moiety) was identified for antileishmanial activity. Optimization of lead 8 provided 24 (containing E-configured aplysinopsin) possessing 10 times more activity and 401-fold less toxicity than the drug pentamidine in cell based assays. Synthesis of 24 was possible, surprisingly, because of two innate reactivities of indole-3-carbaldehyde which provided it in diastereo- and regio-selectively pure form without recourse to the long reaction pathway.