title: The structure-activity relationship of the antimalarial ozonide arterolane (OZ277).
abstract: The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro. Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Dong
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.forename: Kamaraj
authors.initials: K
authors.lastname: Sriraghavan
authors.forename: Jacques
authors.initials: J
authors.lastname: Chollet
authors.forename: Susan A
authors.initials: SA
authors.lastname: Charman
authors.forename: William N
authors.initials: WN
authors.lastname: Charman
authors.forename: Christian
authors.initials: C
authors.lastname: Scheurer
authors.forename: Heinrich
authors.initials: H
authors.lastname: Urwyler
authors.forename: Josefina
authors.initials: J
authors.lastname: Santo Tomas
authors.forename: Christopher
authors.initials: C
authors.lastname: Snyder
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Creek
authors.forename: Julia
authors.initials: J
authors.lastname: Morizzi
authors.forename: Maria
authors.initials: M
authors.lastname: Koltun
authors.forename: Hugues
authors.initials: H
authors.lastname: Matile
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.forename: Maniyan
authors.initials: M
authors.lastname: Padmanilayam
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Tang
authors.forename: Arnulf
authors.initials: A
authors.lastname: Dorn
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Vennerstrom
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D010545:Peroxides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D006573:Heterocyclic Compounds, 1-Ring; D010545:Peroxides; D013141:Spiro Compounds; C489136:arterolane