A NEW CLASS OF CHEMOTHERAPEUTIC AGENTS ORALLY EFFECTIVE AGAINST SCHISTOSOMIASIS JAPONICA

Hundreds of compounds bearing the following broad structure have been synthesized by us lately in pursuance of non-antimonial chemotherapeutic agent effective against schistosomiasis japonica; many of them were found to possess pronounced activity in animal tests. Where (X=-NO₂; halogens; -CH₃; -NHR'etc.) R=halogens; H; -CH₃; -C₂H₅; -C₃H₇; -C₄H₉; -CN; n=0; 1; 2; B=-OR"'; -SR""; various amines; hydrazie; sustituted piperazines; sulphonamides; amino acids,etc. Two of the compounds, coded as F-30066(X=NO₂; R=H; B=-NHCH(CH₃)₂; n=1) and F-30069(X=NO₂; R=H; B— -NHCH₂COOC₂H₅; n=1) have passed on to clinical trials and favourable results have been reported. Animal tests were performed by workers of the Institute of Parasitology, Chinese Academy of Medical Sciences. F-30066 was shown to possess both prophylactic and curative activity against experimental infections in mice; the rate of elimination of worms reached 100%; and the respective rates in rabbits and dogs were 97—100% and 85—91%. In vitro, a concentration of 3.25 γ/ml was inhibitory to the worm. Clinical observations have been carried out at several districts. According to reports upon 202 cases by the Chiasin Schistosomiasis Prevention and Cure Hospital, the drug has been stated as notably effective when administered, to patients with acute schistosomiasis japonica and highly febrile patients with schistosomiasis japonica of a later stage; the body temperatures were brought to normal at an average of 6-day intervals after the commencement of the therapy. Symptomatic improvements in various degrees were also recorded in chronic and early cases. The immediate negative conversion rate of stool specimens in acute cases was 31—64%. Clinical reports upon 225 cases from Chanshu and Shanghai have given similar results. The late (4—8 months) negative conversion rate in acute cases was 41.6%. Main side effects of the drug were muscular spasms and irritations to the gastro-intestinal tract, but no serious intoxication had been encountered. However, as psychoneurotic symptoms could easily be evoked in patients whose hepatic functions were subnormal, it is therefore contra-indicated. Experimental and clinical effectiveness of F-30069 was found to be basically similar to those of F-30066. Further work on chemical structural variations of this broad class of compounds as well as the biochemistry and the pharmacology of the actions of them are still progressing in various laboratories concerned