Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes.
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.
Dong
Yuxiang
Y
College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA.
Tang
Yuanqing
Y
Chollet
Jacques
J
Matile
Hugues
H
Wittlin
Sergio
S
Charman
Susan A
SA
Charman
William N
WN
Tomas
Josefina Santo
JS
Scheurer
Christian
C
Snyder
Christopher
C
Scorneaux
Bernard
B
Bajpai
Saroj
S
Alexander
Scott A
SA
Wang
Xiaofang
X
Padmanilayam
Maniyan
M
Cheruku
Srinivasa R
SR
Brun
Reto
R
Vennerstrom
Jonathan L
JL
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
C503429:1,2,4-trioxane; D000962:Antimalarials; D006571:Heterocyclic Compounds; D013141:Spiro Compounds