SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF FLUORENEMETHANOLS

For the purpose of improving the oral antimalarial activities of the fluorenemethanols (reported by us in previous articles) which were less effective by oral than by subcutaneous administration, 24α-(alkylaminomethyl)-2,7-dichloro-9-substituted benzylidene-4-fluorenemethanols (III) were synthesized. The results of preliminary screenings demonstrated that five compounds (No.1～4,8) exhibited significant antimalarial activities against Plasmodium berghei NK₆₅ strain in mice by oral administration, at dose of 6.25 mg·kg^-1·d^-1×3 with suppressive rate of 100%. Further evaluation of these 5 compounds showed that 4 of them (No.1～4)were superior to chloroquine in parallel tests, their ED₅₀ and ED₉₀ were 1.0, 1.6; 0.6, 0.9; 0.7, 1.5 and 0.8, 1.6 mg·kg^-1·d^-1×3 respectively, while the ED₅₀ and ED₉₀ of chloroquine were 1.9 and 2.9 mg·kg^-1·d^-1×3 respectively; one compound (No.8) was equal to chloroquine, its ED₅₀ and ED₉₀ were 1.5 and 3.2 mg·kg^-1·d-1×3 respectively. Further assessment of these 4 compounds are in progress.