Mixed tetraoxanes containing the acetone subunit as antimalarials.
Eleven new tetraoxanes possessing cholic acid-derived carrier and isopropylidene moiety were synthesized and were tested in vitro and in vivo. In vitro screening revealed that nine of them were more potent against CQ-resistant W2 than CQ-susceptible D6 strain and that two of them were equally or more potent than artemisinin and mefloquine against multi-drug resistant TM91C235 strain. Amine 8 cured all mice at the dose of 160mg/kg/day, while the anilide 9 exhibited MCD<or=20mg/kg/day. The diol 13 was most potent antiproliferative with GI(50), TGI, LC(50) MG_MID 0.98microM, 3.80microM, 11.22microM, respectively. All tested compounds showed no toxic effects.
Institute of Chemistry, Technology and Metallurgy, Belgrade, Serbia.
Dejan M
DM
Opsenica
Natasa
N
Terzić
Philip L
PL
Smith
Youngsun
Y
Yang
Lalaine
L
Anova
Kirsten S
KS
Smith
Bogdan A
BA
Solaja
D000096:Acetone; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D037621:Artemisinins; D004353:Drug Evaluation, Preclinical; D018432:Drug Resistance, Multiple; D015767:Mefloquine; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D045568:Tetraoxanes / Q000138:chemical synthesis* / Q000494:pharmacology*
D000962:Antimalarials; D037621:Artemisinins; D045568:Tetraoxanes; D000096:Acetone; C031327:artemisinin; D015767:Mefloquine