Synthesis of Selenium-Quinone Hybrid Compounds with Potential Antitumor Activity via Rh-Catalyzed C-H Bond Activation and Click Reactions

In continuation of our quest for new redox-modulating catalytic antitumor molecules, selenium-containing quinone-based 1,2,3-triazoles were synthesized using rhodium-catalyzed C-H bond activation and click reactions. All compounds were evaluated against five types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), SF295 (human glioblastoma cells), NCIH-460 (human lung cells) and PC3 (human prostate cancer cells). Some compounds showed good activity with IC50 values below 1 µM. The cytotoxic potential of the naphthoquinoidal derivatives was also evaluated in non-tumor cells, exemplified by L929 cells. Overall, these compounds represent promising new lead derivatives and stand for a new class of chalcogenium-containing derivatives with potential antitumor activity

Pathogen-Mediated Proteolysis of the Cell Death Regulator RIPK1 and the Host Defense Modulator RIPK2 in Human Aortic Endothelial Cells

Porphyromonas gingivalis is the primary etiologic agent of periodontal disease that is associated with other human chronic inflammatory diseases, including atherosclerosis. The ability of P. gingivalis to invade and persist within human aortic endothelial cells (HAEC) has been postulated to contribute to a low to moderate chronic state of inflammation, although how this is specifically achieved has not been well defined. In this study, we demonstrate that P. gingivalis infection of HAEC resulted in the rapid cleavage of receptor interacting protein 1 (RIPK1), a mediator of tumor necrosis factor (TNF) receptor-1 (TNF-R1)-induced cell activation or death, and RIPK2, a key mediator of both innate immune signaling and adaptive immunity. The cleavage of RIPK1 or RIPK2 was not observed in cells treated with apoptotic stimuli, or cells stimulated with agonists to TNF-R1, nucleotide oligomerization domain receptor 1(NOD1), NOD2, Toll-like receptor 2 (TLR2) or TLR4. P. gingivalis-induced cleavage of RIPK1 and RIPK2 was inhibited in the presence of a lysine-specific gingipain (Kgp) inhibitor. RIPK1 and RIPK2 cleavage was not observed in HAEC treated with an isogenic mutant deficient in the lysine-specific gingipain, confirming a role for Kgp in the cleavage of RIPK1 and RIPK2. Similar proteolysis of poly (ADP-ribose) polymerase (PARP) was observed. We also demonstrated direct proteolysis of RIPK2 by P. gingivalis in a cell-free system which was abrogated in the presence of a Kgp-specific protease inhibitor. Our studies thus reveal an important role for pathogen-mediated modification of cellular kinases as a potential strategy for bacterial persistence within target host cells, which is associated with low-grade chronic inflammation, a hallmark of pathogen-mediated chronic inflammatory disorders

Solar radiation and vertical leaf area distribution in forest - Reserva Biológica do Cueiras ZF02, Manaus

In this work, the vertical leaf area distribution is investigated in connection with radiation regime, using the measurements of solar radiation made om July to November 2001 at the experimental site of Reserva Biológica do Cuieiras, Manaus, ZF2 km 14 and km 34, in Central Amazonia. A sampling technique is used for the radiation measurements inside two tall canopy covers, having a mobile support apparatus, made up of modular ame, which allows placement of the radiation sensors at different heights along a vertical line within the canopy. Inversion of the solar radiation physical model allowed a determination of the leaf area density. Spatial variability of leaf area (LAI, function a(z)) is established for the two experimental sites om the measurements of solar radiation in three verticals on each site. The average values of leaf area index (LAI) for the local vegetation at km 14 and at km 34 ZF2 were 6,4 and 6,1, respectively. A comparative analysis is developed concerning the vertical distributions of leaf area obtained for different experimental sites in Amazonia, using the same solar radiation measurement system.Neste estudo, a distribuição vertical de área foliar em floresta é investigada em conexão com o regime de radiação, usando as medidas de radiação solar realizadas no período de julho a novembro de 2001, na Reserva Biológica do Cuieiras - Manaus ZF2, km 14 e km 34, na Amazônia Central. Técnicas experimentais de amostragem de radiação no interior de coberturas vegetais de grande porte são utilizadas, com dispositivos de suporte móveis constituídos por reticulados modulares, que permitem a disposição dos sensores de radiação em diferentes níveis de uma mesma vertical no interior da cobertura. Inversão de modelos radiativos em coberturas vegetais densas permite as análises sobre a distribuição vertical de área foliar. A variabilidade espacial de área foliar (IAF, função a(z)) é estabelecida para os dois sítios experimentais a partir de medidas de radiação solar, individualizadas em três verticais em cada um desses locais. O índice de área foliar total médio (IAF) da vegetação local para o sítio experimental do km 14 alcançou o valor de 6,4 e para o sítio experimental do km 34 o valor de 6,1. Uma análise comparativa é desenvolvida sobre distribuições verticais de área foliar obtidas em sítios experimentais da Amazônia, usando o mesmo sistema de medidas de radiação solar