Molecular orbital studies of antischistosomal agents.

Molecular orbital calculations were used to investigate the antischistosomal agent, niridazole, and an inactive derivative, 1-(5-nitro-2-thiazolyl)-2-ethylurea. The CNDO/2 calculations revealed that the inactive derivative had a preferred conformation stabilized by an intramolecular hydrogen bond. The molecular profile, the relative three-dimensional arrangement of constituent atoms, of the inactive derivative was different than that of the niridazole compound. The likelihood of similar intramolecular interactions rendering niridazole derivatives inactive is discussed. The results of the calculations suggest select structural modifications that might increase the efficacy of niridazole derivatives.