title: Synthesis, stability, and antimalarial activity of new hydrolytically stable and water-soluble (+)-deoxoartelinic acid.
abstract: (+)-Deoxoartelinic acid (13), a new hydrolytically stable, water-soluble, and potent non-acetal-type antimalarial drug candidate, was successfully prepared from artemisinic acid by using sulfur ylide and photooxygenative cyclization in seven steps. This compound showed superior in vitro antimalarial activity against the chloroquine-resistant K1 strain of Plasmodium falciparum and higher suppression (98.7%) than arteether in vivo against Plasmodium chabaudi infected mice. (+)-Deoxoartelinic acid also showed remarkable stability with a half-life of 258.66 h, 23 times more stable than clinically useful arteether in simulated stomach acid, and improved solubility, 4 times more soluble than artemisinin in water.
authors.affiliation: Department of Chemistry, Yonsei University, Seoul 120-749, Korea. mkjung@alchemy.yonsei.ac.jp
authors.forename: Mankil
authors.initials: M
authors.lastname: Jung
authors.forename: Kyunghoon
authors.initials: K
authors.lastname: Lee
authors.forename: Howard
authors.initials: H
authors.lastname: Kendrick
authors.forename: Brian L
authors.initials: BL
authors.lastname: Robinson
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006868:Hydrolysis; D008288:Malaria / Q000401:mortality; D051379:Mice; D010961:Plasmodium / Q000187:drug effects; D012995:Solubility; D013237:Stereoisomerism
chemical_list: D000962:Antimalarials; D006575:Heterocyclic Compounds, 3-Ring; C467717:deoxoartelinic acid; D002738:Chloroquine