Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin

Abstract

Cancer constitutes the second main mortality cause in the world, after cardiovascular diseases. In spite of the progresses in the chemotherapeutics treatments, many patients fail chemotherapy, mainly because of side effects or multidrugs resistance, proving the need and importance of the research for new molecules with anticancer activity, more effective and with smaller adverse effects. Various compounds derived from plant secondary metabolites are commonly used in the chemotherapy against cancer and the natural products play an important role in the research for new molecules. Among several molecules of natural origin evaluated by MTT assay in murine tumor cell lines [breast (LM3) and lung (LP07)] the quinonamethide triterpenes tingenone and pristimerin showed marked cytotoxic activity presenting IC50 around 2 and 5 µM respectively. The structure-activity relationship suggests that rings A and B containing an α, ß-unsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between these positions and acetylcisteyne residues suggests a probable mechanism of action. The in vitro mutagenic activity was also evaluated by the Salmonella microsome assay (Ames test) for pristimerin and tingenone with and without metabolic activation (S9) in the strains TA98, TA97a, TA100 and TA102, none of which showed mutagenic potential in any strains. Estrogenic and anti-estrogenic activities were also studied by the e-screen assay in MCF-7 cells with negative results. The present data point to the importance of pristimerin and tingenone as representative of an emerging class of potential anticancer chemicals.

Antidiarrheal activity of extracts from Maytenus gonoclada and inhibition of Dengue virus by lupeol

“…In previous studies on low polarity extracts from M. gonoclada three new pentacyclic triterpenes were isolated, and the triterpenes from friedelane series were predominant (Silva et al 2011a, b, 2013, Oliveira et al 2007). The tingenone (4) isolated from hexane/ethyl ether and chloroform extracts from roots is the secondary metabolite isolated exclusively from roots of plants from Celastraceae, and is considered a chemotaxonomic marker to this family (Gomes et al 2011). …”

Cytotoxic effect of Semialarium mexicanum (Miers) Mennega root bark extracts and fractions against breast cancer cells

“…Although there are few studies on the cytotoxic activity of S. mexicanum, there are several reports about the activity of the quinone methide triterpenes pristimerin and tingenone present in S. mexicanum, as well as other members of the Celestraceae family. These two molecules have promising potential as therapeutic and chemopreventive agents against cancer (Gomes et al 2011). The cytotoxic activity of pristimerin has been evidenced in different cancer-derived cell lines and animal models.…”

Effect of constituents from samaras of Austroplenckia populnea (Celastraceae) on human cancer cells

“…Some studies with species of the Celastraceae family show positive results for the anticancer activity [ 3 , 4 ]. Constituents isolated from species of the Celastraceae family such as sesquiterpenes, agarofurans and pentacyclic triterpenes present proven antitumoral properties [ 5 - 7 ].…”

“…Constituents isolated from species of the Celastraceae family such as sesquiterpenes, agarofurans and pentacyclic triterpenes present proven antitumoral properties [ 5 - 7 ]. Among these triterpenes, it has been reported that tingenone and pristimerin, frequently found in different species of the Celastraceae family, present potential properties against cancer cell lines [ 3 ].…”