Suwito Hery, Pudjiastuti Pratiwi, Fanani Much Zaenal, Kimata-Ariga Yoko, Katahira Ritsuko, Kawakami Toru, Fujiwara Toshimichi, Hase Toshiharu, Sirat Hasnah Mohd, Puspaningsih Ni Nyoman Tri
Department of Chemistry, Faculty of Science and Mathematics, University of Gajah Mada, Jogjakarta 55281, Indonesia.
Department of Pharmacology and Therapy, Faculty of Medicine, University of Gajah Mada, Jogjakarta 55281, Indonesia.
Molecules. 2014 Dec 19;19(12):21473-88. doi: 10.3390/molecules191221473.
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.
一些查耳酮已通过克莱森-施密特反应设计并合成出来，作为铁氧化还原蛋白和铁氧化还原蛋白-NADP⁺还原酶相互作用的抑制剂，以寻求一种新型的选择性抗疟药物。合成的化合物对恶性疟原虫铁氧化还原蛋白-恶性疟原虫铁氧化还原蛋白-NADP⁺还原酶（PfFd-PfFNR）表现出10.94%-50%的抑制作用。（E）-1-（4-氨基苯基）-3-（4-甲氧基苯基）丙-2-烯-1-酮（50%）、（E）-1-（4-氨基苯基）-3-（2,4-二甲氧基苯基）丙-2-烯-1-酮（38.16%）和（E）-1-（4-氨基苯基）-3-（2,3-二甲氧基苯基）丙-2-烯-1-酮（31.58%）表现出最强的三种抑制活性。通过对接实验我们确定，甲氧基氨基查耳酮衍生物的氨基通过盐桥的静电相互作用在抑制活性中起重要作用，并且它与铁氧化还原蛋白-NADP⁺还原酶（FNR）形成的复合物比与铁氧化还原蛋白（Fd）形成的复合物更稳定且亲和力更好。
