Molecular Pharmacology, Vol 6, 604-616, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Relationship between Structure, Conformation, and Antischistosomal Activity of Nitroheterocyclic Compounds

¹ Department of Pharmacology and Experimental Therapeutics, School of Medicine, and Department of Pathobiology, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205

The biochemical and chemotherapeutic effects of a number of nitroheterocyclic compounds, including niridazole [1-(5-nitro-2-thiazolyl)-2-imidazolidinone] and some 5-nitro-2-furyl derivatives, on Schistosoma mansoni were investigated. Those compounds which had marked schistosomicidal activity had common structural and conformational features. These comprised a 5-nitrothiazolyl or 5-nitrofuryl ring, with a nitrogen substituent (generally part of an amide or oxadiazole system) attached to C-2 via a rigid side chain. The latter contains either a C=C double bond or a nitrogen atom attached directly to C-2 of the heterocyclic ring. These features, which are illustrated in the accompanying structure, are believed to be

See PDF for Equation

essential for significant antischistosomal activity. The schistosomicidal effects of compounds of this structural type were invariably preceded by a reduction of phosphorylase phosphatase activity in the worms, suggesting a common mode of action.

Note:
ACKNOWLEDGMENTS We are indebted to Dr. Arnold D. Welch of the Squibb Institute for Medical Research and to Dr. Herman Breuer of the Heyden Chemical Company for the nitrofurans, to Dr. Ashton C. Cuckler and Dr. William C. Campbell of Merck and Company for aminitrozole, to Dr. Edward F. Elslager of Parke, Davis and Company for the nitrosonaphthylamine, as well as to all of the above for the mouse diets in which many of these compounds had been incorporated, to Dr. Gerald Berkelhammer of American Cyanamid Company for the pyridine- and quinoline-substituted nitrothiazoles, and to Miss Geraldine Rose and Miss Mary Pyles for valuable technical assistance.

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