Six lycorine derivatives were prepared, characterized, and evaluated for their in vitro anti-Trichomonas vaginalis activity. Compounds bearing an acetyl (2), lauroyl (3), benzoyl (4 and 5), and pnitrobenzoyl (6 and 7) groups were synthesized. The best activity was achieved with lycorine esterified at C-2 position with lauroyl group. Preliminary structure-activity relationship points that unprotected OH group at C-1 and C-2 is not necessary to the antiparasitic activity, and none of the derivative was less active than lycorine. The lycorine structural requisites required to kill this amitochondriate cell seem to be different in comparison with the derivatives most active against other parasites and tumor cell lines, both mitochondriated cells. This result is an important contribution with our ongoing studies regarding the mechanism of action of the Amaryllidaceae alkaloids on T. vaginalis cell death opening a new perspective to optimize this innovative pharmacological potential.Key words: alkaloid, Amaryllidaceae, Hippeastrum, lycorine derivatives, Trichomonas vaginalis Trichomonas vaginalis is a flagellate protozoan that infects the human urogenital tract and causes trichomonosis, the most common non-viral sexually transmitted disease (1). The factors considered to be involved in the pathogenicity of T. vaginalis include the ability of trichomonads to adhere to vaginal epithelial cells (2), the cytotoxic effect of the pathogen on host cells, trichomonad proteinase activity (3), and the ability of trichomonads to produce subcutaneous abscess lesions in mice (4). Complications related to trichomonosis include infertility (5), cervical cancer (6), pelvic inflammatory disease (7), birth outcomes, and increase in human immunodeficiency virus (HIV) transmission and acquisition (8).Metronidazole and tinidazole are two drugs of choice recommended by Food and Drug Administration (FDA, USA) for the treatment of human trichomonosis (9). However, its potential carcinogenicity in rats and mutagenicity in bacteria, when administered at high doses for protracted periods of time (10,11), have been harmful. Reports on metronidazole-resistant isolates of T. vaginalis have increased, besides common adverse reactions (12)(13)(14). To improve the current chemotherapy of T. vaginalis infection, natural products as well as synthetic compounds could be a source of new antiprotozoal drugs with high activity, low toxicity, and alternative mechanisms of action.Our ongoing studies regarding the anti-T. vaginalis activity of natural products, specially on Amaryllidaceae alkaloids, have showed interesting results. Crude extracts of alkaloids and isolated compounds from several Amaryllidaceae species showed antitrichomonas activity (15). The investigation of the mechanism of action implicated, using the alkaloids lycorine and candimine, demonstrated that the extracellular ATP and adenosine levels could be modulated by these compounds, and it could be relevant in increasing susceptibility of T. vaginalis to host immune response in the presence...

Genistein modulates inflammatory responses in part by reducing the production of the pro-inflammatory cytokines IL-12, TNF-a, and nitric oxide, by activated macrophages in response to lipopolysaccharide stimulus. Previous studies have shown that synthetic lipophilic genistein glycosides were significantly more active than hydrophilic glycosides. The aims of this study were to synthesize and to evaluate the effect of novel lipophilic genistein derivatives on IL-12, TNF-a, and nitric oxide production by J774A.1 cells. The results show that the modification of genistein enables the generation of non-cytotoxic compounds with increased IL-12 inhibition. However, these derivatives failed to inhibit TNF-a. The nitric oxide production was notably inhibited by the monoester (2, 3) and monoether (6, 7) compounds in a dose-dependent manner.