Design, synthesis and activity against Staphylococcus epidermidis of 5-chloro-2-or 5-chloro-4-methyl-9H-xanthen-9-one and some of its derivatives
CHEMICAL BIOLOGY & DRUG DESIGN
Authors: Mazur, Gabriela; Skiba-Kurek, Iwona; Karczewska, Elzbieta; Panczyk-Straszak, Katarzyna; Jaworska, Joanna; Waszkielewicz, Anna M.
Abstract
Ten new xanthone derivatives have been designed and synthesized for their potential antibacterial activity. All compounds have been screened against Staphylococcus epidermidis strains ATCC 12228 and clinical K/12/8915. The highest antibacterial activity was observed for compound 3: 5-chloro-2-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)-9H-xanthen-9-one dihydrochloride, exhibiting MIC of 0.8 mu g/ml against ATCC 12228 strain, compared to linezolid (0.8 mu g/ml), ciprofloxacin (0.2 mu g/ml) or trimethoprim and sulfamethoxazole (0.8 mu g/ml). For the most active compound 3, genotoxicity assay with use of Salmonella enterica serovar Typhimurium revealed safety in terms of genotoxicity at concentration 75 mu g/ml and antibacterial activity against Salmonella at all higher concentrations. A final in silico prediction of skin metabolism of compound 3 seems promising, indicating stability of the xanthone moiety in the metabolism process.
Prenatal programming of the immune response induced by maternal periodontitis: Effects on the development of acute lung injury in rat pups
LIFE SCIENCES
Authors: Wuo, Alexandre do Valle; Klein, Simone; de Almeida, Patricia; Marcos, Rodrigo Labat; de Souza Setubal Destro, Maria Fernanda; de Fatma, Daniela Teixeira; Ratto Tempestini Horliana, Anna Carolina; Lino-dos-Santos-Franco, Adriana
Abstract
Aims: Oral cavity pathogens play an important systemic role, modulating the development of several diseases. Periodontitis is a very common oral disease associated with dental biofilm. It is characterized by gum inflammation, periodontal ligament degeneration, dental cementum and alveolar bone loss. Studies point to the association between maternal periodontitis and adverse outcomes during pregnancy. However, they did not evaluate the impact of maternal periodontitis in the offspring. Thus, our objective was to investigate the effects of maternal periodontitis in the immune system of offspring. Material and methods: For this evaluation we induced acute lung injury in rat pups. Pregnant rats were submitted or not to periodontitis by ligature technique. Thirty days after the birth, offspring was submitted to acute lung inflammation by administration of lipopolysaccharide (LPS, Salmonella abortus equi, 5 mg/kg, ip). Key findings: Our results showed that maternal periodontitis increased myeloperoxidase activity, the levels of TNF-alpha and IL-17A in the bronchoalveolar fluid, the gene expression of TNF-alpha, IL-17A, and cyclooxygenases 1 and 2. In addition, maternal periodontitis did not alter the number of leukocytes migrated into the lung, tracheal responsiveness, expression of TLR4 and NF-KB translocation. Significance: This study showed prenatal programming of the immune response induced by maternal period-ontitis, and reinforces the importance of oral health care during pregnancy.