Cyclohexene-fused 1, 3-oxazines with selective antibacterial and antiparasitic action and low cytotoxic effects. (October 2017)

• Record Type: Journal Article
• Authors: de Brito, Maria R.M.; Peláez, Walter J.; Faillace, Martín S.; Militão, Gardenia C.G.; Almeida, Jackson R.G.S.; Argüello, Gustavo A.; Szakonyi, Zsolt; Fülöp, Ferenc; Salvadori, Maria C.; Teixeira, Fernanda S.; Freitas, Rivelilson M.; Pinto, Pedro L.S.; Mengarda, Ana C.; Silva, Marcos P.N.; Da Silva Filho, Ademar A.; de Moraes, Josué
• Is Part Of: Toxicology in vitro. Volume 44(2017)
• Page Start: 273
• Page End: 279
• Publication Date: 2017-10
• Subjects: Cyclohexene-fused 1, 3-Oxazines -- Anthelmintic activity -- Antimicrobial activity -- Schistosoma mansoni; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2017.07.021
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: 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 ( cis ‑1-benzyl- N -phenyl-1, 4, 4a, 5, 8, 8a-hexahydro-3, 1-benzoxazin-2-imine (1 ) and trans ‑ N -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 oxazine2 is more effective against bacteria than oxazine1, with the lowest MIC and MBC values of 3.91 and 32.5 μg/mL, respectively. Similarly, compound2 demonstrated higher antiparasitic activity than1, 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. Highlights: Oxazine2 exhibited antischistosomal activity against Schistosoma mansoni Oxazine2 displayed activity against Staphylococcus aureus and Escherichia coli Oxazine2 caused death and tegumental damage of adult S. mansoni worms Oxazines exhibited low cytotoxic effects on human cancer cell lines.