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 8provided 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 24was 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. [ABSTRACT FROM AUTHOR]