Chemopreventive potential of natural products isolated from a alchornea glandulosa, pterogyne nitens and its semisynthetic analogs

Chemoprevention involves the use of natural or synthetic substances to reduce the risk of developing cancer. Gallic acid was found to possess several pharmacological activities, such as anti-oxidant and anti-inflammatory. Guanidine alkaloids display a broad spectrum of biological activities and its cytotoxic effect were well investigated. OBJECTIVES: The present study evaluated the chemopreventive potential of natural products and its semi-synthetic analogs using quinone reductase (QR) induction, aromatase inhibition and the suppression of NFκB activity, which are well established strategies for screening compounds to cancer chemoprevention. METHODS: Gallic acid was isolated from Alchornea glandulosa, and alkyl gallates were prepared from the reaction of the corresponding alcohols with gallic acid or from the reaction with acetic anhydride. The guanidine alkaloids nitensidines A and B were isolated from Pterogyne nitens. All compounds were evaluated for QR induction using murine hepatoma cell line Hepa 1c1c7 and two mutant cell lines; for in vitro aromatase inhibition; and against TNFα-induced NFκB activation with stable transfected 293/NFκB-Luc human embryonic kidney cells. Compounds were tested at 20Bg/mL following 1:3 serial dilutions. RESULTS: No QR induction was observed at tested concentrations. Nitensidine A and B showed aromatase inhibition (IC50 18,3 ± 8,7 uM), but moderately cytotoxic to Hepa 1c1c7 cells (IC50 5,7 ± 0,6 uM). With IC50 values in a range of 10 to 50 μM, all the gallic acid esters mediated NFκB inhibitory activity. In addition, gallic acid mediated a modest cytotoxic effect, but none of the gallate esters affected cell viability at the tested concentrations. CONCLUSION: Based on these intracellular responses, we suggest that gallate esters are related to suppression of NFκB activation, which it could play a chemopreventive role in carcinogenesis