Cyclohexene-fused 1,3-oxazines with selective antibacterial and antiparasitic action and low cytotoxic effects

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

TOXICOLOGY IN VITRO : AN INTERNATIONAL JOURNAL PUBLISHED IN ASSOCIATION WITH BIBRA.

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2017 vol. 44 p. 273 - 279

0887-2333

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,ShigellaflexneriandStaphylococcusaureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC).Additionally, theex vivoantiparasitic activity of oxazines was assessed againstSchistosoma mansoni, a helminththat is one of the major agents of the disease schistosomiasis Also, oxazines were evaluated on three tumor celllines, NCI-H292 (human lung carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (human cervixcarcinoma), and two normal cell lines (Vero and red blood cells). Bioassays revealed that oxazine2is moreeffective against bacteria than oxazine1,with the lowest MIC and MBC values of 3.91 and 32.5μg/mL, respectively. Similarly, compound 2demonstrated higher antiparasitic activity than1,and scanning electronmicroscopy analysis showed several morphological alterations in the tegument of worms in a concentrationdependent 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.