Anthelmintic Activity of 3-methyl-5-[(p-nitrophenyl)azo]rhodanine

Abstract

A new antiparasitic agent, 3-methyl-5-[(p-nitrophenyl)azo]rhodanine, "Nitrodan," was effective when administered in feed against Hymenolepis nana and Syphacia obvelata infections in mice, Ascaridia galli infections in chickens, and Toxocara canis, Ancylostoma caninum, and Uncinaria stenocephala infections in dogs. This drug was not effective against Aspiculuris tetraptera, Nematospiroides dubius, and Nippostrongylus muris in mice or Toxascaris leonina in dogs. Nitrodan fed for 21 days at levels of 250 to 1,000 ppm produced significant destrobilization of H. nana in mice but removed few of the scolices. Levels of 500 to 1,000 ppm nitrodan fed for 21 days were 86 to 90% effective in reducing the numbers of adult and immature S. obvelata in mice. Nitrodan administered at 250 and 500 ppm for 4 weeks against artificial laboratory infections of A. galli was 59 and 94% effective. Comparable levels of 230 and 460 ppm nitrodan fed for 6 weeks or longer under field conditions were 94 to 100% effective which indicated lengthening the feeding period increased efficacy. In dogs, nitrodan exhibited activity against T. canis, A. caninum, and U. stenocephala by reducing egg production prior to promoting gradual elimination of the worms. Nitrodan levels of 100 to 500 ppm rapidly reduced T. canis egg production and worm burdens, and produced efficient, but not complete, removal of both hookworm species in 4 to 8 weeks. A method of initial drug evaluation using five species of helminths in mice is also presented. Recent reports of efficacy of relatively longterm feeding of anthelmintic drugs to rats (Cuckler et al., 1965), dogs (Wood, et al., 1965), poultry (Boisvenue and Hendrix, 1965), swine (Isenstein and Todd, 1965), and cattle (Cox et al., 1965) suggest this method of controlling parasitism may prove more efficient in animal production than individual dosage administration (s). Candidate compounds for continuous feeding require maximum tolerance by the host but theoretically offer maximum opportunity for antiparasitic effect. The mechanisms involved for chemoprophylactic elimination of helminth populations may be quite different from the more conventional vermifuge action sought by single or intermittent drug administration. Nitrodan is representative of a new class of antiparasitic drugs. CH:--N-C=O I S=C C-N=N7 -NO2