Constituants chimiques, propriétés cytotoxiques, antifongiques et antibactériennes de l’extrait chloroforme de Centaurea diluta Ait. subsp. algeriensis (Coss. & Dur.) Maire

Abstract

This work is apart of our researchunit program relating to the phytochemical and biological studies on the plants of the genus Centaurea (Asteraceae). The species of this genus are potential reserves of bioactive secondary metabolites. The present work concerned initially the in vitro evaluation of the cytotoxic, antifungal and direct and indirect antimicrobial activities of the chloroform soluble part of the hydro-alcoholic extract of the aerial parts of Centaurea diluta Ait. subsp. algeriensis (Coss. & Dur.) Maire, an endemic species to Algeria and Morocco. According to an exhaustive bibliographical research carried out on Centaurea species, no phytochemical nor biological report is available on this subspecies so far; which constitutes one of our selection criteria for this plant. Inactive against 7 tested microorganisms (plant pathogens) fungi, bacteria and yeast, and also inactive in the direct antibacterial test, this extract displayed significant cytotoxic effects on cancer cells (the A549 non-small-cell lung carcinoma, the MCF7 breast adenocarcinoma and the U373 glioblastoma). In indirect antibacterial tests, the CHCl3 extract was able to potentiate the effect of -lactam antibiotics on methicillin-resistant Staphylococcus aureus (MRSA), reducing the minimal inhibitory concentrations (MICs) by a factor of 2-32-fold. No synergy was found between the extract and streptomycin. Biological data allowed to guide the chemical composition of the extract by fractionation, separation and purification on silica gel 60 (CC and TLC). This study led to the isolation of nine components in a pure state and the identification of five of them, by the combination of several spectroscopic analyses. These products were two phenolic compounds (vanillin 1, paridol 3), a lignane [(-arctigenin 2] and two flavonoid aglycones (eupatilin 4 and jaceosidin 5). All the isolated compounds are described for the first time for this species. The 5 identified compounds were evaluated for cytotoxic and antimicrobial activities. Moderate cytotoxic effects were observed on the six tested cancer cell lines (A549, MCF7, U373, Hs683 human glioma, PC3 human prostate and B16-F10 murine melanoma) for both the flavonoid aglycones and the lignane with IC50s in the range 28 μM to 40 μM. In the direct antibacterial test by TLCbioautography, among the five isolated compounds, only jaseosidin 5 showed a moderate antimicrobial activity but this activity was relatively weak on the positive and negative Gram bacteria (MIC of 200 μg/mL on MRSA C98506, MRSA C100459, MRSA ATCC33591, MSSA ATCC6538, E. coli ATCC25922).