Eur J Med Chem. 2009 Sep;44(9):3810-5. Epub 2009 Apr 14.

Antiproliferative activity of arborescidine alkaloids and derivatives.

Santos LS, Theoduloz C, Pilli RA, Rodriguez J.

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Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Universidad de Talca, Av. Lircay s/n, Talca, P.O. Box 747, Chile. lssantos@utalca.cl

Abstract

Current issues in cancer research involve searching for novel anticancer compounds that can be used to regulate the cell cycle and lead to more effective treatments of tumors. In this study, it was hypothesized that possessing a cyclic alkaloid similar to harmine, arborescidines can disrupt the proliferative state of cancer cells and block the activity of topoisomerases. The antiproliferative activity of arborescidines A-C and their derivatives was evaluated in vitro against four human tumor cell lines: gastric adenocarcinoma, lung cancer, bladder carcinoma and leukemia. Assuming the mechanism of action by topoisomerase II binding model, the compounds possessing the greatest activity had nonpolar side-chain into hydrophobic binding region on the DNA/topo II complex.

PMID:: 19419803; [PubMed - indexed for MEDLINE]

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