- Novel HIV-1 integrase inhibitors derived from quinolone antibiotics.
Novel HIV-1 integrase inhibitors derived from quinolone antibiotics.
Journal of medicinal chemistry (2006-03-03)
Motohide Sato, Takahisa Motomura, Hisateru Aramaki, Takashi Matsuda, Masaki Yamashita, Yoshiharu Ito, Hiroshi Kawakami, Yuji Matsuzaki, Wataru Watanabe, Kazunobu Yamataka, Satoru Ikeda, Eiichi Kodama, Masao Matsuoka, Hisashi Shinkai
PMID16509568
ABSTRACT
The viral enzyme integrase is essential for the replication of human immunodeficiency virus type 1 (HIV-1) and represents a remaining target for antiretroviral drugs. Here, we describe the modification of a quinolone antibiotic to produce the novel integrase inhibitor JTK-303 (GS 9137) that blocks strand transfer by the viral enzyme. It shares the core structure of quinolone antibiotics, exhibits an IC50 of 7.2 nM in the strand transfer assay, and shows an EC50 of 0.9 nM in an acute HIV-1 infection assay.