RESUMO
Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and transN-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Additionally, the ex vivo antiparasitic activity of oxazines was assessed against Schistosoma mansoni, a helminth that is one of the major agents of the disease schistosomiasis Also, oxazines were evaluated on three tumor cell lines, NCI-H292 (human lung carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (human cervix carcinoma), and two normal cell lines (Vero and red blood cells). Bioassays revealed that oxazine 2 is more effective against bacteria than oxazine 1, with the lowest MIC and MBC values of 3.91 and 32.5µg/mL, respectively. Similarly, compound 2 demonstrated higher antiparasitic activity than 1, and scanning electron microscopy analysis showed several morphological alterations in the tegument of worms in a concentration-dependent manner. In contrast, both oxazines exhibited low cytotoxic effects on cancer and normal cell lines. These results indicated that oxazines exerted direct effects on bacteria and parasite schistosomes. More importantly, since schistosomiasis control programs rely on one drug, praziquantel, oxazines may have the potential to become new antischistosomal agents.
Assuntos
Antibacterianos/farmacologia , Cicloexenos/farmacologia , Oxazinas/farmacologia , Esquistossomicidas/farmacologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/ultraestrutura , OvinosRESUMO
Blood fluke of the genus Schistosoma are the etiological agents of human schistosomiasis, an important neglected tropical disease that afflicts over 200 million people worldwide. The treatment for this disease relies heavily on a single drug, praziquantel. Recent reports of praziquantel resistance raise concerns about future control of the disease and show the importance of developing new antischistosomal drugs. Currently, natural products have been a good source for drug development. (+)-Limonene epoxide is a mixture of cis and trans isomers found in many plants. Here, we report the in vitro effect of this natural compound on the survival time of Schistosoma mansoni adult worms. In addition, we examined alterations on the tegumental surface of adult schistosomes by means of confocal laser scanning microscopy. The effects of (+)-limonene epoxide at 25 µg/mL on S. mansoni adult worms were similar to those of the positive control (praziquantel), with reduction in motility and death of all worms after 120 h. Confocal laser scanning microscopy revealed that (+)-limonene epoxide-mediated worm killing was associated with tegumental destruction. Our results, along with the low toxicity of the (+)-limonene epoxide, suggest that this natural compound might be promising for the development of new schistosomicidal agents.