Carbamoyl Alkyl Phosphorodithioates as Chemotherapeutic Agents: Screening by Aedicidal Properties in Laboratory Mammals, Lambs and Calves1

Abstract

Procedures are given for the use of a mouse-mosquito (Aedes aegypti (L.)) test, and supplementary tests in other mammals, in screening and evaluating compounds for chemotherapeutic activity. Nine of thirteen known insecticides given orally to mice killed mosquitoes feeding on them, including six out of seven compounds known to be effective against cattle grubs. The most active of 19 carbamoyl alkyl phophorodithioates tested was O, O,-dimethyl-S-(N-methylcarbamoylmethyl) phosphorodithioate (Am. Cyanamid 12,880). This had an ED₅₀ in mice, lambs and calves of about 6 mg./kg., with a chemotherapeutic index (LD₅₀/ED₅₀) of about 25 in mice. In lambs and calves, about seven times the ED₅₀ for mosquitoes produced marked toxic symptoms. Structure-activity relationships in the carbamoyl alkyl phosphorodithioates indicated a marked superiority of O, O,-dimethyl compounds over corresponding O, O,-diethyl analogs. The few higher O, O,-alkyls tested were uninteresting. In the O, O-dimethyl series, the unsubstituted carbamoyl group was less than one-twentieth as active as the methyl carbamoyl.