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Molecules. 2014 Dec 19;19(12):21473-88. doi: 10.3390/molecules191221473.

Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents.

Author information

1
Department of Chemistry, Faculty of Science and Mathematics, University of Gajah Mada, Jogjakarta 55281, Indonesia. herys08032002@yahoo.com.
2
Department of Chemistry, Faculty of Science and Mathematics, University of Gajah Mada, Jogjakarta 55281, Indonesia.
3
Department of Pharmacology and Therapy, Faculty of Medicine, University of Gajah Mada, Jogjakarta 55281, Indonesia.
4
Department of Chemistry, Faculty of Science and Technology, Airlangga University, Surabaya 60115, Indonesia.
5
Institute of Tropical Disease, Airlangga University, Surabaya 60115, Indonesia.
6
Institute of Protein Research, Osaka University, 3-2 Yamadoaka, Suita-Shi, Osaka 656-0871 Japan.
7
Department of Chemistry, Faculty of Science, University Technology Malaya, Johor Bahru 81310, Malaysia.

Abstract

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.

PMID:
25532844
PMCID:
PMC6271513
DOI:
10.3390/molecules191221473
[Indexed for MEDLINE]
Free PMC Article

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