Design and Synthesis of Chalcone Derivatives as Inhibitors of the Ferredoxin — Ferredoxin-NADP+ Reductase Interaction of Plasmodium falciparum: Pursuing New Antimalarial Agents

Some chalcones have been designed and synthesized using Claisen-Schmidt reactions as inhibitors of the ferredoxin and ferredoxin-NADP+ reductase interaction to pursue a new selective antimalaria agent. The synthesized compounds exhibited inhibition interactions between PfFd-PfFNR in the range of 10....

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Bibliographic Details
Main Authors: Hery Suwito, Jumina, Mustofa, Pratiwi Pudjiastuti, Much Zaenal Fanani, Yoko Kimata-Ariga, Ritsuko Katahira, Toru Kawakami, Toshimichi Fujiwara, Toshiharu Hase, Hasnah Mohd Sirat, Ni Nyoman Tri Puspaningsih
Format: Article
Language:English
Published: MDPI AG 2014-12-01
Series:Molecules
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Online Access:http://www.mdpi.com/1420-3049/19/12/21473
Description
Summary:Some chalcones have been designed and synthesized using Claisen-Schmidt reactions as inhibitors of the ferredoxin and ferredoxin-NADP+ reductase interaction to pursue a new selective antimalaria agent. The synthesized compounds exhibited inhibition interactions between PfFd-PfFNR in the range of 10.94%–50%. The three strongest inhibition activities were shown by (E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (50%), (E)-1-(4-aminophenyl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one (38.16%), and (E)-1-(4-aminophenyl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one (31.58%). From the docking experiments we established that the amino group of the methoxyamino chlacone derivatives plays an important role in the inhibition activity by electrostatic interaction through salt bridges and that it forms more stable and better affinity complexes with FNR than with Fd.
ISSN:1420-3049