[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, 24 alpha-(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 x 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 x 3 respectively, while the ED50 and ED90 of chloroquine were 1.9 and 2.9 mg.kg-1. d-1 x 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 x 3 respectively. Further assessment of these 4 compounds are in progress.
Deng
R X
RX
Institute of Microbiology and Epidemiology, Military Academy of Medical Sciences, Beijing 100071.
Zhong
J X
JX
Zhao
D C
DC
Zhang
H B
HB
Sheng
X Y
XY
Ding
D B
DB
Yang
J D
JD
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D005449:Fluorenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D008288:Malaria / Q000188:drug therapy*; D000432:Methanol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D015394:Molecular Structure; D010962:Plasmodium berghei
D000962:Antimalarials; D005449:Fluorenes; D000432:Methanol