Juan José Nogal

In vitro screening of American plant extracts on Trypanosoma cruzi and Trichomonas vaginalis

From the beginning of this decade and with the revival of the phytotherapy, biological research about immunomodulatory, anti-inflammatory and antiprotozoal effects of Central and South American plants have been in progress. Our objective was to determine the antiprotozoal activity of 79 extracts from different plant families, including Asteraceae, Araceae, Moraceae, Solanaceae, Rhamnaceae, Zingiberaceae, Leguminosae and Sapotaceae. Once matching with herbarium specimens authenticated the plants, selected parts were separated, dried carefully and reduced to powder. Most of the screened extracts were aqueous. Two protozoa with different metabolic pathways, Trypanosoma cruzi and Trichomonas vaginalis were used as experimental models. Trypanocidal activity of plants was assayed on epimastigote cultures in liver infusion tryptose (LIT). Anti-Trichomonas activity was determined over cultures of the parasite in Diamond medium. In both cases, microscopic counting of parasites, after their incubation in the presence of different concentrations of the crude extracts, were made in order to determine the cytocidal and cytostatic activities respect to control cultures. Of the nine extracts that showed antiprotozoal activity, those from Mikania cordifolia and Philodendron bipinnatifidum were then fractionated, and again, were assayed the organic and aqueous phases obtained.

New Antitrichomonal Drug-like Chemicals Selected by Bond (Edge)-Based TOMOCOMD-CARDD Descriptors

Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental results to a great extent because a correct classification for both models of 95.24% (20 of 21) of the chemicals was obtained. Of the 21 compounds that were screened and synthesized, 2 molecules (chemicals G-1, UC-245) showed high to moderate cytocidal activity at the concentration of 10 μg/ml, another 2 compounds (G-0 and CRIS-148) showed high cytocidal activity only at the concentration of 100 μg/ml, and the remaining chemicals (from CRIS-105 to CRIS-153, except CRIS-148) were inactive at these assayed concentrations. Finally, the best candidate, G-1 (cytocidal activity of 100% at 10 μg/ml) was in vivo assayed in ovariectomized Wistar rats achieving promising results as a trichomonacidal drug-like compound. (Journal of Biomolecular Screening 2008:785-794).

In Vitro Antiparasitic Activity of Plant Extracts from Panama

As a contribution to the search of antiparasitic activity in plants from Panama, a total of 37 extracts obtained from 14 species were assessed against Trypanosoma cruzi (Trypanosomatidae), Trichomonas vaginalis (Trichomonadidae), and Heligmosomoides polygyrus (Heligmosomidae). Also, the cytotoxicity to macrophages was determined, in order to discard, among the active extracts, those cytotoxic to mammalian cells. Tripanocidal activity and cytotoxicity to macrophages were performed by a colorimetric method using the tetrazolium salt MTT, assays on T. vaginalis by counting viable protozoa, and the anthelmintic activity was determined by enzymatic assays of acetylcholinesterase and acid phosphatase activities. Extracts from Bixa orellana L. (Bixaceae) and Clusia rosea Jacy. (Clusiaceae) were the most interesting both as antiprotozoan and nematocides.