Synthesis and Biological Evaluation of Prodigiosene Analogues

Abstract

Prodigiosenes are a family of tripyrrolic 4-methoxypyrrolyl-dipyromethane natural products based on the parent compound, prodigiosin. Prodigiosin exhibits significant anti-cancer activity including some ability to specifically target breast cancer cells. By appending targeting moieties to these compounds with known selectivity for carcinomas, the prodigiosene selectivity should be enhanced and the corresponding residual toxicities lowered. Targeting groups chosen for use in this study include estrogens and anti-estrogens, porphyrins and glucose. Following known synthetic strategies, prodigiosenes with appended targeting moieties were synthesized, via an ester or amide linker. MTT assays using human breast cancer cell lines MCF-7 and MDA-MB231 were performed for each of the conjugates and the results demonstrate promise for the targeting strategy. A cell viability screen was also performed on a prodigiosene-estrone conjugate against the NCI60 cell line and demonstrated differential activity for the compound.