title: Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes.
abstract: Based on the structures of several lipophilic trioxolane antimalarial prototypes, we set out to determine which functional groups were associated with good antimalarial profiles and identify more polar (lower LogP/LogD) lead compounds with good physicochemical properties. More lipophilic trioxolanes tended to have better oral activities than their more polar counterparts. Trioxolanes with a wide range of neutral and basic, but not acidic, functional groups had good antimalarial profiles.
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: Yuanqing
authors.initials: Y
authors.lastname: Tang
authors.forename: Jacques
authors.initials: J
authors.lastname: Chollet
authors.forename: Hugues
authors.initials: H
authors.lastname: Matile
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.forename: Susan A
authors.initials: SA
authors.lastname: Charman
authors.forename: William N
authors.initials: WN
authors.lastname: Charman
authors.forename: Josefina Santo
authors.initials: JS
authors.lastname: Tomas
authors.forename: Christian
authors.initials: C
authors.lastname: Scheurer
authors.forename: Christopher
authors.initials: C
authors.lastname: Snyder
authors.forename: Bernard
authors.initials: B
authors.lastname: Scorneaux
authors.forename: Saroj
authors.initials: S
authors.lastname: Bajpai
authors.forename: Scott A
authors.initials: SA
authors.lastname: Alexander
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.forename: Maniyan
authors.initials: M
authors.lastname: Padmanilayam
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Cheruku
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Vennerstrom
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C503429:1,2,4-trioxane; D000962:Antimalarials; D006571:Heterocyclic Compounds; D013141:Spiro Compounds