A PRELIMINARY NOTE ON THE RELATIONSHIP BETWEEN STRUCTURE AND ANTISCHISTOSOMAL ACTIVITY OF NITROFURAZONES

The semicarbazone of 5-nitro-2-furaldehyde (nitrofurazone, Furacin) (I) has been shown to be a broadspectrum antibacterial agent and possesses certain antiparasitic activities. We have tested its therapeutico-prophylactic effects on mice experimentally infected with Schistosoma japonicum, and it is found that nitrofurazone has shown chemoprophylactic activity against schistosomiasis japonica. Several groups of compounds are therefore synthesized to be related to nitrofurazone. They are: derivatives other than semicarbazone of 5-nitro-2-furaldehyde, derivatives of 5-nitro-2-furyl-acrolein, derivatives of p-(or o-)nitrobenzaldehyde, derivatives of p-nitroacetophenone and β-(5-nitro-2-furyl)acrylamindes. Among these compounds, 5-nitro-2-furylaldehyde thiosemicarbazone, 5-nitto-2-furyl-acrolein semicarbazone and thiosemicarbazone, 4-methyl-l-β-(5-nitro-2-furyl)acryl-piperazine, 4-benzyl-l-β- (5-nitro-2-furyl)-acryl-piperazine, 4-diethylcarbamyl-l-β-(5-nitro-2-furyl)acryl-piperazine, N-methyl-β-(5-nitro-2-furyl)acryl amide and N-β-(5-nitro-2-furyl)acryl-ethyleneimide have shown chemoprophylactic activity against schistosomiasis japonica in mice, but the final two compounds possess chemotherapeutic activity as well. The results of our preliminary experiments may illustrate the following facts: (1) The 5-nitro-2-furaldehyde thiosemicarbazone possesses also chemoprophylactic activity, as is isostere of nitro-furazone. (2) The increase of one double bond in the nitrofurazone molecule dose not lose the chemoprophylactic activity. It is believed that certain relationship between the effect of conjugated system and antischistosomal activity is existing. (3) All the benzene analogs of furan have been proved to be ineffective against schis-tosomulae, and it is thought that the principle of analogy could not be applied in this case. (4) The nitrofurazone is found to possess prophylactic activity against schistosomiasis japonica only, but the β-(5-nitro-2-furyl)acrylamides are proved to be both prophylactic and therapeutic. (5) The antischistosomal activity of nitrofurazones is related to O₂N—O—CH= group and also to the elongation of its conjugated double bond system.