Document Detail


Synthesis of isoquinuclidine analogs of chloroquine: antimalarial and antileishmanial activity.
MedLine Citation:
PMID:  17400457     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The isoquinuclidine (2-azabicyclo[2.2.2]octane) ring system may be viewed as a semi-rigid boat form of the piperidine ring and, when properly substituted, a scaffold for rigid analogs of biologically active ethanolamines and propanolamines. It is present in natural products (such as ibogaine and dioscorine) that display interesting pharmacological properties. In this study, we have expanded our continuing efforts to incorporate this ring system in numerous pharmacophores, by designing and synthesizing semirigid analogs of the antimalarial drug chloroquine. The analogs were tested in vitro against Plasmodium falciparum strains and Leishmania donovani promastigote cultures. Compounds 6 and 13 displayed potent antimalarial activity against both chloroquine-susceptible D6 and the -resistant W2 strains of P. falciparum. All analogs also demonstrated significant antileishmanial activity with compounds 6 and 13 again being the most potent. The fact that these compounds are active against both chloroquine-resistant and chloroquine-sensitive strains as well as leishmanial cells makes them promising candidates for drug development.
Authors:
M O Faruk Khan; Mark S Levi; Babu L Tekwani; Norman H Wilson; Ronald F Borne
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2006-11-16
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  15     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-04-30     Completed Date:  2007-07-30     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  3919-25     Citation Subset:  IM    
Affiliation:
Department of Medicinal Chemistry, University of Mississippi, University, MS 38677, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimalarials / chemical synthesis*,  pharmacology
Antiprotozoal Agents / chemical synthesis*,  pharmacology
Chloroquine / analogs & derivatives*
Leishmania / drug effects*
Plasmodium falciparum / drug effects*
Quinuclidines / chemical synthesis*
Grant Support
ID/Acronym/Agency:
U50/CCU423310//PHS HHS
Chemical
Reg. No./Substance:
0/Antimalarials; 0/Antiprotozoal Agents; 0/Quinuclidines; 54-05-7/Chloroquine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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