Experimental and theoretical studies of anthelmintics: oxfendazole and its imidazo[1,2-a]pyridine-2-carbamate isomer.
Mice experimentally infected with Trichinella spiralis were used to test the therapeutic effectiveness of an anthelmintic, methyl 6-(phenylsulfinyl)imidazo[1,2-a]pyridine-2-carbamate, against the immature and adult worms during the intestinal phase of infection. A single oral dose of 100 mg kg-1 of the drug on the third day after exposure to infection was totally ineffective against the adult worms as determined at necropsy on day 6. Neither higher unit dosages of the drug, division of the daily oral dose, nor increasing the length of the treatment period from 1 to 4 days enhanced drug activity in vivo. Furthermore the drug was inactive as a single oral dose against the immature worms at all of the dosages tested (12.5-400 mg kg-1). These results are in marked contrast to those obtained previously with oxfendazole (methyl 5[6]-(phenylsulfinyl)benzimidazole-2-carbamate) under comparable experimental conditions and clearly indicate that the two compounds are not anthelmintically equivalent in the T. spiralis-infected mouse system in spite of their similar structural features. A quantum mechanical study of these drugs was undertaken and a hypothesis for the inactivity of the imidazo[1,2-a]pyridine-2-carbamate isomer is proposed.
R O
RO
McCracken
K B
KB
Lipkowitz
D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D007536:Isomerism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D014235:Trichinellosis / Q000188:drug therapy*
D000871:Anthelmintics; D001562:Benzimidazoles; C011030:oxfendazole