Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes

Yuxiang Dong; Yuanqing Tang; Jacques Chollet; Hugues Matile; Sergio Wittlin; Susan A Charman; William N Charman; Josefina Santo Tomas; Christian Scheurer; Christopher Snyder; Bernard Scorneaux; Saroj Bajpai; Scott A Alexander; Xiaofang Wang; Maniyan Padmanilayam; Srinivasa R Cheruku; Reto Brun; Jonathan L Vennerstrom

doi:10.1016/j.bmc.2006.05.041

Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes

Bioorg Med Chem. 2006 Sep 15;14(18):6368-82. doi: 10.1016/j.bmc.2006.05.041. Epub 2006 Jun 8.

Authors

Yuxiang Dong¹, Yuanqing Tang, Jacques Chollet, Hugues Matile, Sergio Wittlin, Susan A Charman, William N Charman, Josefina Santo Tomas, Christian Scheurer, Christopher Snyder, Bernard Scorneaux, Saroj Bajpai, Scott A Alexander, Xiaofang Wang, Maniyan Padmanilayam, Srinivasa R Cheruku, Reto Brun, Jonathan L Vennerstrom

Affiliation

¹ College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA.

PMID: 16759871
DOI: 10.1016/j.bmc.2006.05.041

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimalarials / chemical synthesis
Antimalarials / chemistry
Antimalarials / pharmacology*
Heterocyclic Compounds / chemical synthesis
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology*
In Vitro Techniques
Molecular Conformation
Parasitic Sensitivity Tests
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry
Spiro Compounds / pharmacology*
Stereoisomerism
Structure-Activity Relationship

Substances

1,2,4-trioxane
Antimalarials
Heterocyclic Compounds
Spiro Compounds