New derivatives of 3,5-substituted-1,4,2-dioxazoles: Synthesis and activity against Entamoeba histolytica

Dioxazole derivatives (1–33) were synthesized in two steps via their corresponding oximes (I–III). All the compounds were characterized using various spectroscopic techniques. A comparative study of in vitro antiamoebic activity of these heterocyclic compounds, viz. 3-o-chloro (1–11), 3-m-chloro (12–22) and 3-p-chloro (23–33) dioxazoles having same substituents at 5-position of dioxazole ring, was performed against HM1:IMSS strain of Entamoeba histolytica. The results showed a regular pattern in the activity and out of 33 compounds assayed 15 compounds showed better antiamoebic activity than metronidazole with IC50 values in the range 0.41–1.73 μM and 1.80 μM. Dioxazoles having o-chloro, m-chloro, p-chloro, dichloro and pyridine substituents at 5-position were more active than the standard drug metronidazole. The toxicity studies against human kidney epithelial cell line showed that all the compounds were non-toxic. 3,5-Bis-[2-chlorophenyl]-1,4,2-dioxazole (10) was most active and least toxic among all the compounds.

Analogues of dioxazoles (1–33) having substitution at 3- and 5-position were synthesized. The in vitro antiamoebic activity of these compounds was carried out against HM1:IMSS strain of Entamoeba histolytica. Out of 33 compounds 15 had better IC50 values than the standard drug metronidazole. The MTT studies on human kidney epithelial cell line showed that all the compounds were non-toxic.Figure optionsDownload as PowerPoint slide