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 IC(50) values in the range 0.41-1.73 microM and 1.80 microM. 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.
Bhat
Abdul R
AR
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Athar
Fareeda
F
Azam
Amir
A
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D004748:Entamoeba histolytica / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000166:cytology; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010091:Oximes; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D010080:Oxazoles; D010091:Oximes