title: Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents.
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.
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Gajah Mada, Jogjakarta 55281, Indonesia. herys08032002@yahoo.com.
authors.forename: Hery
authors.initials: H
authors.lastname: Suwito
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Gajah Mada, Jogjakarta 55281, Indonesia.
authors.lastname: Jumina
authors.affiliation: Department of Pharmacology and Therapy, Faculty of Medicine, University of Gajah Mada, Jogjakarta 55281, Indonesia.
authors.lastname: Mustofa
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Airlangga University, Surabaya 60115, Indonesia.
authors.forename: Pratiwi
authors.initials: P
authors.lastname: Pudjiastuti
authors.affiliation: Institute of Tropical Disease, Airlangga University, Surabaya 60115, Indonesia.
authors.forename: Much Zaenal
authors.initials: MZ
authors.lastname: Fanani
authors.affiliation: Institute of Protein Research, Osaka University, 3-2 Yamadoaka, Suita-Shi, Osaka 656-0871 Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kimata-Ariga
authors.affiliation: Institute of Protein Research, Osaka University, 3-2 Yamadoaka, Suita-Shi, Osaka 656-0871 Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Katahira
authors.affiliation: Institute of Protein Research, Osaka University, 3-2 Yamadoaka, Suita-Shi, Osaka 656-0871 Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Institute of Protein Research, Osaka University, 3-2 Yamadoaka, Suita-Shi, Osaka 656-0871 Japan.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Institute of Protein Research, Osaka University, 3-2 Yamadoaka, Suita-Shi, Osaka 656-0871 Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Hase
authors.affiliation: Department of Chemistry, Faculty of Science, University Technology Malaya, Johor Bahru 81310, Malaysia.
authors.forename: Hasnah Mohd
authors.initials: HM
authors.lastname: Sirat
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Airlangga University, Surabaya 60115, Indonesia.
authors.forename: Ni Nyoman Tri
authors.initials: NN
authors.lastname: Puspaningsih
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis*; D001665:Binding Sites; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D015195:Drug Design; D005287:Ferredoxin-NADP Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D005288:Ferredoxins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D062105:Molecular Docking Simulation; D010940:Plant Proteins / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000962:Antimalarials; D005288:Ferredoxins; D010940:Plant Proteins; D015800:Protozoan Proteins; D002599:Chalcone; D005287:Ferredoxin-NADP Reductase