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Abstract: A series of 15-membered azalide urea and thiourea derivatives has been synthesized and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (D6), chloroquine/pyremethamine resistant (W2) and multidrug resistant (TM91C235) strains of Plasmodium falciparum. We have developed an effective automated synthetic strategy for the rapid synthesis of urea/thiourea libraries of a macrolide scaffold. Compounds have been synthesized using a solution phase strategy with overall yields of 50–80%. Most of the synthesized compounds had inhibitory effects. The top 10 compounds were 30–65 times more potent than azithromycin, an azalide with antimalarial activity, against all three strains. [Copyright &y& Elsevier]

Abstract: 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⩽20mg/kg/day. The diol 13 was most potent antiproliferative with GI50, TGI, LC50 MG_MID 0.98μM, 3.80μM, 11.22μM, respectively. All tested compounds showed no toxic effects. [Copyright &y& Elsevier]