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Title: New efflux pumps inhibitors for Gram positive bacteria strains and cancer cells from an African medicinal plant
Authors: Ramalhete, Cátia
Spengler, G
Serley, J
Duarte, N
Viveiros, M
Amaral, L
Molnár, J
Mulhovo, S
Ferreira, MJU
Keywords: African medicinal plant
Gram positive bacteria
Issue Date: 2009
Citation: 2º Congresso Iberoamericano de Fitoterapia
Abstract: All living cells contain genes encoding multidrug transporters and some of them play an important role in conferring drug resistance in mammalian cancer cells and in microbial pathogens such as Staphylococcus aureus, Enterococcus faecalis, Candida albicans, Plasmodium falciparum, and Leishmania donovani. The over-expression of P- glycoprotein (P-gp) is one of the principal mechanisms of multidrug resistance (MDR) found in eukaryotic and prokaryotic cells (Fig.1). The inhibition of P-gp as a possible way of reversing MDR has been extensively studied. A large number of plant-derived compounds and synthetic molecules have been shown to block MDR pump efflux activity. Nevertheless, their pharmacokinetic interaction with chemotherapy and side effects have limited their clinical development.1 In our search for biologically active compounds from Momordica balsamina L. (Fig.2), we have isolated and characterized three new cucurbitane-type triterpenes, named balsaminagenin A and B, and balsaminoside A (1-3) and a known cucurbitacin (4). The isolated compounds (Fig.3) were evaluated for their efflux modulating effects of Gram positive and negative bacteria by a real-time fluorimetric method that utilizes the fluorochrome ethidium bromide (EB), a universal substrate of bacterial efflux pumps. Furthermore, the evaluation of the compounds as P-gp modulators of resistant cancer cells was also carried out by flow cytometry, using rhodamine 123, and by real-time fluorometry method, the latter method assessing accumulation of EB on a real-time basis.
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