A New Class of Potential Chloroquine-Resistance Reversal Agents for Plasmodia:  Syntheses and Biological Evaluation of 1-(3‘-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines

1-(3‘-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2000-09, Vol.43 (18), p.3428-3433
Main Authors: Batra, Sanjay, Srivastava, Pratima, Roy, Kamal, Pandey, V. C, Bhaduri, A. P
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials - chemical synthesis
Antimalarials - chemistry
Antimalarials - pharmacology
Antiparasitic agents
Biological and medical sciences
Chloroquine - pharmacology
Drug Resistance
Drug Resistance, Multiple
Heme - antagonists & inhibitors
Heme - metabolism
Heme Oxygenase (Decyclizing) - antagonists & inhibitors
Heme Oxygenase (Decyclizing) - metabolism
Hemeproteins - antagonists & inhibitors
Hemeproteins - metabolism
Medical sciences
Mice
Pharmacology. Drug treatments
Plasmodium - drug effects
Plasmodium - metabolism
Pyrrolidines - chemical synthesis
Pyrrolidines - chemistry
Pyrrolidines - pharmacology
Structure-Activity Relationship
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Summary:1-(3‘-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the results are presented. The possible mode of action of the compounds of this series is by inhibition of the enzyme heme oxygenase, thereby increasing the levels of heme and hemozoin, which are lethal to the parasite.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm000083u