Identification of New Inhibitors with Potential Antitumor Activity from Polypeptide Structures via Hierarchical Virtual Screening.

Leukemias are neoplasms that affect hematopoietic cells, which are developed by genetic alterations (mutations) that lead to the loss of proliferation control mechanisms (maturation and/or cell death). The α4ß1 integrin receptor is a therapeutic target for inflammation, autoimmune diseases and lymphoid tumors. This study was carried out to search through the antagonists-based virtual screening for α4ß1 receptor. Initially, seventeen (17) structures were selected (based on the inhibitory activity values, IC50) and the structure with the best value was chosen as the pivot. The pharmacophoric pattern was determined from the online PharmaGist server and resulted in a model of score value equal to 97.940 with 15 pharmacophoric characteristics that were statistically evaluated via Pearson correlations, principal component analysis (PCA) and hierarchical clustering analysis (HCA). A refined model generated four pharmacophoric hypotheses totaling 1.478 structures set of Zinc_database. After, the pharmacokinetic, toxicological and biological activity predictions were realized comparing with pivot structure that resulted in five (ZINC72088291, ZINC68842860, ZINC14365931, ZINC09588345 and ZINC91247798) structures with optimal in silico predictions. Therefore, future studies are needed to confirm antitumor potential activity of molecules selected this work with in vitro and in vivo assays.

Morphology of the testes and epididymal ducts in the pampas cat Leopardus colocolo (Molina, 1782) / Morfologia dos testículos e ductos epididimários do gato-palheiro Leopardus colocolo (Molina, 1782)

The pampas cat Leopardus colocolo (Molina, 1782) is a species of the Felidae family, widely distributed in South America, included on CITES Appendix II and classified as Near Threatened on the IUCN Red List, with population trend decreasing. Based on this information, the objective of this study is to describe morphologically the testes and epididymal ducts of pampas cat. The animal, coming from the Federal University of Mato Grosso Zoo, Brazil, had died after anesthesia procedure and the male reproductive system was dissected to collect the testicles. The samples taken were fragmented and histologically examined. From the microscopic analysis of the testes were identified: vaginal and tunica albuginea, formed by dense connective tissue modeled with large amount of collagen fibers. The tunica albuginea fibrous septa emits into the body. The seminiferous tubules are coiled and coated internally by spermatogenic epithelium consisting of Sertoli cells, surrounded by a basement membrane in the presence of myoid cells. The interstitial tissue between the seminiferous tubules, is composed of loose connective tissue, blood and lymph vessels, and Leydig cells in polyhedral shape. The epididymal ducts showed pseudostratified columnar epithelium with secretory cells of which stereocilia design, situated on a basement membrane filled by myoid cells. This epithelium has principal and basal cells, the main cell design stereocilia toward the lumen of the epididymal duct.(AU)

O gato-palheiro Leopardus colocolo (Molina, 1782) é uma espécie da família Felidae, com ampla distribuição na América do Sul. Está incluido no Appendix II da CITES e classificada como Próxima da Extinção na Lista Vermelha da IUCN, apresentando população em decrescimo. Com base nessas informações o objetivo deste estudo é caracterizar morfologicamente os testículos e ductos epididimários de L. colocolo. O animal, oriundo do Zoológico da Universidade Federal de Mato Grosso, Brasil, veio a óbito após procedimento anestésico e o sistema reprodutor masculino foi dissecado para coleta dos testículos. As amostras retiradas foram fragmentadas e histologicamente examinadas. A partir das análises microscópicas dos testículos foram identificados: a túnica vaginal e albugínea, formada por tecido conjuntivo denso modelado, com grande quantidade de fibras de colágeno. A túnica albugínea emite septos fibrosos para o interior do órgão. Os túbulos seminíferos são enovelados e revestidos internamente por epitélio estratificado constituído por células espermatogênicas e células somáticas de Sertoli, envolvidos por uma membrana basal com presença de células mioides. O tecido intersticial, entre os túbulos seminíferos, é constituído de tecido conjuntivo do tipo frouxo com vasos sanguíneos e linfáticos, e células de Leydig em formato poliédrico. Os ductos epididimários apresentaram epitélio cilíndrico pseudoestratificado com células secretoras dos quais projetam estereocílios, situados sobre uma membrana basal repleta por células mióides. Este epitélio apresenta células principais e basais, cujas células principais projetam estereocílios em direção ao lúmen do ducto epididimário.(AU)