학술논문
NaturalProduct Derived Antiprotozoal Agents: Synthesis,Biological Evaluation, and Structure–Activity Relationshipsof Novel Chromene and Chromane Derivatives.
Document Type
Article
Author
Source
Subject
*NATURAL products
*ANTIPROTOZOAL agents
*STRUCTURE-activity relationship in pharmacology
*SCAFFOLD proteins
*AMIDE synthesis
*PHENOLS
*LEAD compounds
*THERAPEUTICS
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Language
ISSN
0022-2623
Abstract
Variousnatural products with the chromane and chromene scaffoldexhibit high antiprotozoal activity. The natural product encecalin(7) served as key intermediate for the synthesis of differentethers 9, amides 11, and amines 12. The chromane analogues 14and the phenols 15were obtained by reductive amination of ketones 13and 6, respectively. Angelate 3, ethers 9, and amides 11did not show considerable antiprotozoalactivity. However, the chromene and chromane derived amines 12, 14, and 15revealed promisingantiprotozoal activity and represent novel lead compounds. Whereasbenzylamine 12aand α-methylbenzylamine 12gwere active against P. falciparumwith IC50values in the range of chloroquine, the analogous phenols 15aand 15bwere unexpectedly 10- to 25-foldmore potent than chloroquine with selectivity indexes of 6760 and1818, respectively. The phenylbutylamine 14dbased onthe chromane scaffold has promising activity against T. bruceirhodesienseand L. donovani. [ABSTRACT FROM AUTHOR]