In vivo Antimalarial Activity of α-Mangostin and the New Xanthone δ-Mangostin.

Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α-mangostin and a new compound, δ-mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α-Mangostin was more active against the resistant Plasmodium falciparum chloroquine-resistant (FCR3) strain (IC50 = 0.2 ± 0.01 µM) than δ-mangostin (IC50 = 121.2 ± 1.0 µM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances.

General strategy for the synthesis of B1 and L1 prostanoids: synthesis of phytoprostanes (RS)-9-L1-PhytoP, (R)-9-L1-PhytoP, (RS)-16-B1-PhytoP, and (RS)-16-L1-PhytoP.

In this paper we describe a novel general synthetic approach to B1- and L1-type phytoprostanes, which are formed in vivo from free-radical-catalyzed nonenzymatic peroxidation of α-linolenic acid (1). The synthesis of phytoprostanes (RS)-9-L1-PhytoP (5), (R)-9-L1-PhytoP (5a), (RS)-16-B1-PhytoP (6), and (RS)-16-L1-PhytoP (7) exemplifies this strategy. The common starting compound 8 has been proved to be synthetically equivalent to a cyclopent-2-en-1-one synthon having opposite donor and acceptor properties at carbons α and ß, respectively. Key steps include the chemoselective lithiation of a 1-iodo-2-bromoolefin, the introduction of the side chains by transition-metal catalysis following Heck- or Suzuki-type protocols, the construction of an enone moiety by a mild Au(I)-catalyzed Meyer Schuster rearrangement, and a lipase-mediated hydrolysis of methyl esters to deliver the phytoprostanes as free carboxylic acids.