Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10592340 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
The plasmepsins are specific aspartic proteases of the malaria parasite and a potential target for developing new antimalarial agents. Our previously reported peptidomimetic plasmepsin inhibitor with modified 2-aminoethylamino substituent, KNI-10740, was tested against chloroquine sensitive Plasmodium falciparum, D6, to be highly potent, however, the inhibitor exhibited about 5 times less activity against multi-drug resistant parasite (TM91C235). We hypothesized the potency reduction resulted from structural similarity between 2-aminoethylamino substituent of KNI-10740 and chloroquine. Then, we modified the moiety and finally identified compound 15d (KNI-10823), that could avoid drug-resistant mechanism of TM91C235 strain.
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Authors
Takuya Miura, Koushi Hidaka, Yukiko Azai, Keisuke Kashimoto, Yuko Kawasaki, Shen-En Chen, Renato Ferreira de Freitas, Ernesto Freire, Yoshiaki Kiso,