ISOLATION AND ANALYSIS OF COMPOUNDS WITH ANTI-TRYPANOSOMAL AND ANTI-CANCER ACTIVITY

Abstract

ABSTRACT

ISOLATION AND ANALYSIS OF COMPOUNDS WITH ANTI-TRYPANOSOMAL AND ANTI-CANCER ACTIVITY

Anuradha Liyana Pathiranage

Project 1

Synthesis and evaluation of ether-linked demethylepipodophyllotoxin dimers.

A series of novel ether-linked dimers of demethylepipodophyllotoxin are topoisomerase II poisons that exhibit higher levels of double-stranded versus single-stranded DNA cleavage than their corresponding monomers. The dimers also have higher levels of tumor cell cytotoxicity than the monomers, lending support to the two-drug model for interaction of demethylepipodophyllotoxins with human topoisomerase IIα.

Project 2

Antitrypanosomal activity of iridals from Iris domestica.

The petroleum ether extract of Iris domestica (Belamcanda chinensis) has been evaluated for activity against Trypanosoma brucei. Bioassay-guided fractionation led to the isolation of four known iridals as the active components. Chemical modification of these isolates afforded novel stable derivatives that maintained bioactivity. This is the first known report of the antitrypanosomal activity of these compounds.