Assessment of estrogenic, mutagenic and antimutagenic activity of nemorosone

Abstract

Currently, a wide range of research involving natural products is focused on the discovery of new drugs in many different therapeutic areas. A great number of the synthetic compounds on the market were derived from natural products, especially plants. Nemorosone is the major constituent of the floral resin of Clusia rosea Jacq., Clusiaceae, and in Cuban propolis. In vitro studies have shown cytotoxic activity in this substance against various tumor cell lines, including those resistant to various cytotoxic drugs, whereas it has low cytotoxicity to non-tumoral cells. Therefore, in order to characterize the biological activity of nemorosone, a substance with potential antitumor activity, and in view of preclinical testing of the toxicity of drug candidate compounds, the main aim of this study was to determine the mutagenic and antimutagenic activity of nemorosone by the Ames test, using the strains TA97a, TA98, TA100 and TA102 of Salmonella typhimurium. Secondly, to characterize the estrogenic activity in an experimental recombinant yeast model (Recombinant Yeast Assay) mutagenic activity was observed at in any of the concentrations in any of the test strains. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine (NPD), mitomycin C (MMC) and aflatoxin B1 (AFL). Nemorosone showed moderate antimutagenic activity (inhibition level 31%), in strain TA100 in the presence of AFL, and strong antimutagenic activity in TA102 against MMC (inhibition level 53%). Estrogenic activity was observed, with an EEq of 0.41±0.16 nM at various tested concentrations.

Advances in Pharmacological Activities and Chemical Composition of Propolis Produced in Americas

“…The mutagenic and antimutagenic activity of nemorosone were assessed by the Ames test on Salmonella typhimurium strains (TA97a, TA98, TA100 and TA102), wherein nemorosone did not induce any mutagenic activity; meanwhile, nemorosome exhibited a moderate to strong protective effect (31 and 53% of inhibition, respectively) in association with mutagens in strains TA100 and TA102. Nemorosone induced estrogenic activity detectable by recombinant yeast assay at various concentrations (EEq of 0.41 ± 0.16 nM), concluding with those results that nemorosone could have a chemotherapeutic application in breast cancer research [120].…”

Evaluation of DNA Damage in HepG2 Cells and Mutagenicity of Garcinielliptone FC, A Bioactive Benzophenone

“… reported that the benzophenone acuminophenone A, which was isolated from Rheedia acuminata , was not mutagenic to several S. Typhimurium strains (TA98, TA100, TA102, TA1537 and TA1538). Similarly, nemorosone was not mutagenic to strains TA97, TA98, TA100 and TA102 , suggesting that other benzophenones, like GFC, do not induce gene mutations.…”

Evaluation of estrogenic, antiestrogenic and genotoxic activity of nemorosone, the major compound found in brown Cuban propolis

“…The ERs agonist activity of nemorosone by RYA was already evaluated by Camargo et al [20] and the results showed an absence of estrogenicity by its benzophenone. These results show that nemorosone does not have the capacity of binding to the ER and mediating the transcription in an agonist away (causing the same effects of the estradiol), but also reduces the capacity of 17 E 2 to exercise this function.…”

“…On the other hand, the compound presented antimutagenic activity, reducing DNA damages induced by the antitumoral mytomicin C [20]. In the order to complement the above results, in view of the outstanding antiproliferative potential of nemorosone and the small number of studies published on its mechanisms of action, the aim of the present investigation was to assess the possible capacity of benzophenone to interact with ERs, by RYA and E-screen assays, and to determine, by comet assay, if the compound causes DNA-damage in tumoral and non-tumoral breast cells.…”