RESUMO
Sunscreening chemicals protect against damage caused by sunlight most absorbing UVA or UVB radiations. In this sense, 2-(2'-hydroxyphenyl)benzoxazole derivatives with amino substituents in the 4' and 5' positions have an outstandingly high Sun Protection Factor and adequate photostability, but their toxicity is not yet known. This study aimed to evaluate the toxicity of three synthetic 2-(2'-hydroxyphenyl)benzoxazole derivatives for their possible application as sunscreens. In silico tools were used in order to assess potential risks regarding mutagenic, carcinogenic, and skin sensitizing potential. Bioassays were performed in L929 cells to assess cytotoxicity in MTT assay and genotoxic activities in the Comet assay and micronucleus test. Also, the Salmonella/microsome assay was performed to evaluate gene mutations. The in silico predictions indicate a low risk of mutagenicity and carcinogenicity of the compounds while the skin sensitizing potential was low or inconclusive. The 2-(4'-amino-2'-hydroxyphenyl)benzoxazol compound was the most cytotoxic and genotoxic among the compounds evaluated in L929 cells, but none induced mutations in the Salmonella/microsome assay. The amino substituted at the 4' position of the phenyl ring appears to have greater toxicological risks than substituents at the 5' position of 2-(phenyl)benzoxazole. The findings warrant further studies of these compounds in cosmetic formulations.
Assuntos
Benzoxazóis/toxicidade , Relação Quantitativa Estrutura-Atividade , Protetores Solares/toxicidade , Animais , Benzoxazóis/química , Carcinogênese/efeitos dos fármacos , Linhagem Celular , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade , Salmonella typhimurium/efeitos dos fármacos , Protetores Solares/químicaRESUMO
The use of natural products from herbs may be a therapeutic option in dyslipidemia treatment. Campomanesia xanthocarpa (Mart.) O. Berg (Myrtaceae) leaves have been used to decrease cholesterol levels. However, studies to determine activities of this plant on triglycerides metabolism have received little attention. The aim of this study was to examine anti-hyperlipidemic effects of a C. xanthocarpa aqueous leaf extract (CxAE) and assess protective actions against oxidative stress and DNA damage. The tyloxapol-induced hyperlipidemia model was used in Wistar rats. Rats were treated orally with CxAE either 250 or 500 mg/kg/day for 7 days prior to tyloxapol administration. Biochemical parameters, oxidative stress levels, and genomic instability were assessed in several tissues. CxAE decreased cholesterol and triglyceride levels in serum and hepatic and renal DNA damage in tyloxapol-treated rats. There was no marked effect on the micronucleus frequency in bone marrow. The extract increased catalase activity and decreased glutathione S-transferase activity in kidney tissue. CxAE showed anti-hyperlipidemic effects, improved oxidative parameters, and protected DNA against damage induced by tyloxapol-induced hyperlipidemia, suggesting C. xanthocarpa leaves may be useful in preventing dyslipidemias.Abbreviations: ALP: Alkaline phosphatase; ALT: Aspartate aminotransferase; ANOVA: Analysis of variance; AST: Aspartate aminotransferase; Ator: Atorvastatin; CAT: Catalase; Chol: Cholesterol; CxAE: Campomanesia xanthocarpa aqueous extract; GST: Glutathione S-transferase; HDL: High density cholesterol; i.p.: Intraperitoneal; NCE: Normochromatic erythrocyte; PBS: Phosphate buffer solution; PCE: Polychromatic erythrocyte; ROS: Reactive oxygen species; SD: Standard deviation; SOD: Superoxide dismutase; T: Tyloxapol; TBARS: Thiobarbituric acid reacting substances; TG: Triglyceride.
Assuntos
Dano ao DNA/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Myrtaceae/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/toxicidade , Extratos Vegetais/uso terapêutico , Animais , Folhas de Planta/química , Ratos , Ratos WistarRESUMO
Cosmeceuticals are cosmetics formulated using compounds with medical-like benefits. Though the antiaging effect of carboxyethyl aminobutyric acid (CEGABA) has been discussed, its action mechanism in cosmeceuticals remains unclear. This study assessed the in vitro efficacy and safety of CEGABA. NHI-3T3 mouse fibroblast cell line was treated with two CEGABA concentrations (50 and 500 µmol/L) for 24 h, 48 h, and 72 h. Cytotoxicity and genotoxicity were evaluated by colorimetry (MTT) and the alkaline version of the comet assay, respectively. Flow cytometry and the scratch-wound assay were used to assess cell-cycle phase distributions and cell migration rates. Compared with the untreated control, CEGABA increased cell growth 1.6 times after 72 h, independent of dose. The compound also decreased cell replication time by 4 h. These findings seem to be related with the approximately 1.5-times increase in phase S cells numbers. Importantly, in vitro wound healing improved roughly 20% after treatment with CEGABA for 24 h and persisted after 48 h, indicating culture recovery. The time-dependent proliferation and migration of fibroblasts induced by CEGABA besides the fact that the compound is neither genotoxic nor cytotoxic makes it an ideal candidate in the development of cosmeceuticals in antiaging therapy.
Assuntos
Aminobutiratos/efeitos adversos , Aminobutiratos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cosméticos/efeitos adversos , Cosméticos/farmacologia , Células 3T3 , Envelhecimento/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Camundongos , Testes de MutagenicidadeRESUMO
New effective compounds for tuberculosis treatment are needed. This study evaluated the effects of a series of quinoxaline-derived chalcones against laboratorial strains and clinical isolates of M. tuberculosis. Six molecules, namely N5, N9, N10, N15, N16, and N23 inhibited the growth of the M. tuberculosis H37Rv laboratorial strain. The three compounds (N9, N15 and N23) with the lowest MIC values were further tested against clinical isolates and laboratory strains with mutations in katG or inhA genes. From these data, N9 was selected as the lead compound for further investigation. Importantly, this chalcone displayed a synergistic effect when combined with moxifloxacin. Noteworthy, the anti-tubercular effects of N9 did not rely on inhibition of mycolic acids synthesis, circumventing important mechanisms of resistance. Interactions with cytochrome P450 isoforms and toxic effects were assessed in silico and in vitro. The chalcone N9 was not predicted to elicit any mutagenic, genotoxic, irritant, or reproductive effects, according to in silico analysis. Additionally, N9 did not cause mutagenicity or genotoxicity, as revealed by Salmonella/microsome and alkaline comet assays, respectively. Moreover, N9 did not inhibit the cytochrome P450 isoforms CYP3A4/5, CYP2C9, and CYP2C19. N9 can be considered a potential lead molecule for development of a new anti-tubercular therapeutic agent.