Discovery of Novel Trichomonacidals Using LDA-Driven QSAR Models and Bond-Based Bilinear Indices as Molecular Descriptors

Few Years ago, the World Health Organization estimated the number of adults with trichomoniasis at 170 million worldwide, more than the combined numbers for gonorrhea, syphilis, and chlamydia. To combat this sexually transmitted disease, Metronidazole (MTZ) has emerged, since 1959, as a powerful drug for the systematic treatment of infected patients. However, increasing resistance to MTZ, adverse effects associated to high-dose MTZ therapies and very expensive conventional technologies related to the development of new trichomonacidals necessitate novel computational methods that shorten the drug discover), pipeline. Therefore, bond-based bilinear indices, new 2-D bond-based TOMOCOMD-CARDD Molecular Descriptors (MDs), and Linear Discriminant Analysis (LDA) are combined to discover novel antitrichomonal agents. Generated models, using non-stochastic and stochastic indices, are able to classify correctly the 90.11% (93.75%) and the 87.92% (87.50%) of chemicals in the training (test) sets, respectively. In addition, they show large Matthews' correlation coefficients (C) of 0.80 (0.86) and 0.76 (0.71) for the training (test) sets, respectively. The result of predictions on the 10% full-out cross-validation test also evidences the quality of both models. In order to test the models' predictive power, 12 compounds, already proved against Trichomonas vaginalis (Tv), are screened in a simulated virtual screening experiment. As a result, they correctly classified 9 out of 12 (75.00%) and 10 out of 12 (83.33%) of the chemicals, respectively, which were the most important criteria to validate the models. Finally, in order to prove the reach of TOMOCOMD-CARDD approach and to discover new trichomonacidals, these classification functions were applied to a set of eight chemicals which, in turn, were synthesized and tested toward in vitro activity against Tv. As a result, experimental observations confirm theoretical predictions to a great extent, since it is gained a correct classification of 87.50% (7/8) of chemicals. Biological tests also show several candidates as antitrichomonals, since almost all the compounds [VAM2-(3-8)] exhibit pronounced cytocidal activities of 100% at the concentration of 100 mu g/mL and at 24 h (48 h) but VAM2-2: 99.37% (100%), and it is remarkable that these compounds do not show toxic activity in macrophage assays at this concentration. The Quantitative Structure-Activity Relationship (QSAR) models presented here could significantly reduce the number of synthesized and tested compounds as well as could act as virtual shortcuts to new chemical entities with trichomonacidal activity

Barn owl (Tyto alba) predation on small mammals and its role in the control of hantavirus natural reservoirs in a periurban area in southeastern Brazil

The aim of this study was to inventory the species of small mammals in Uberlândia, Minas Gerais, Brazil, based on regurgitated pellets of the barn owl and to compare the frequency of rodent species in the diet and in the environment. Since in the region there is a high incidence of hantavirus infection, we also evaluate the importance of the barn owl in the control of rodents that transmit the hantavirus. Data on richness and relative abundance of rodents in the municipality were provided by the Centro de Controle de Zoonoses, from three half-yearly samplings with live traps. In total, 736 food items were found from the analysis of 214 pellets and fragments. Mammals corresponded to 86.0% of food items and were represented by one species of marsupial (Gracilinanus agilis) and seven species of rodents, with Calomys tener (70.9%) and Necromys lasiurus (6.7%) being the most frequent. The proportion of rodent species in barn owl pellets differed from that observed in trap samplings, with Calomys expulsus, C. tener and Oligoryzomys nigripes being consumed more frequently than expected. Although restricted to a single place and based on few individuals, the present study allowed the inventory of eight species of small mammals in Uberlândia. The comparison of the relative frequencies of rodent species in the diet and in the environment indicated selectivity. The second most preyed upon species was N. lasiurus, the main hantavirus reservoir in the Cerrado biome. In this way, the barn owl might play an important role in the control of this rodent in the region, contributing to the avoidance of a higher number of cases of hantavirus infection