Abstract
The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC 50 values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.
Original language | English |
---|---|
Pages (from-to) | 5379-5386 |
Number of pages | 8 |
Journal | European Journal of Medicinal Chemistry |
Volume | 46 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2011 |
Bibliographical note
Funding Information:Authors thank Dr. Carmen Cuevas (PharmaMar S.A. Madrid, Spain) for cytotoxicity assays and to Bioinformatic & Molecular Design Research Center (BMDRC, Yonsey University, Seoul, Korea) for complimentary access to preADMET database. BB and LDC thank the respective fellowships from ALFA (ALR/B73011/94.04-6.0275.9) and ALBAN (E07D401988BR) EC Programs. Financial support from FIS-PI-060782 , FIS-PI-052026 , SAF2010-20059 , the “Plan Andaluz de Investigación (BIO199 )” and ISCIII-RICET ( RD06/0021: 0000 , 0018, 0022 ) is also acknowledged.
Keywords
- Imidazoisoindoles
- In vitro assays
- In vivo assays
- Mouse model
- Plasmodium berghei
- Plasmodium falciparum
- Structure-activity relationship
- Synthesis