Novel HIV-1 integrase inhibitors derived from quinolone antibiotics

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

doi:10.1021/jm0600139

Novel HIV-1 integrase inhibitors derived from quinolone antibiotics

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

IRIDeS - Disaster Medical Science Division

Research output: Contribution to journal › Article › peer-review

329 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1506-1508
Number of pages	3
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	5
DOIs	https://doi.org/10.1021/jm0600139
Publication status	Published - 2006 Mar 5

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/jm0600139

Cite this

@article{2f30d4cddb824e48b9fdfa27ad9b954e,

title = "Novel HIV-1 integrase inhibitors derived from quinolone antibiotics",

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.",

author = "Motohide Sato and Takahisa Motomura and Hisateru Aramaki and Takashi Matsuda and Masaki Yamashita and Yoshiharu Ito and Hiroshi Kawakami and Yuji Matsuzaki and Wataru Watanabe and Kazunobu Yamataka and Satoru Ikeda and Eiichi Kodama and Masao Matsuoka and Hisashi Shinkai",

year = "2006",

month = mar,

day = "5",

doi = "10.1021/jm0600139",

language = "English",

volume = "49",

pages = "1506--1508",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "5",

}

TY - JOUR

T1 - Novel HIV-1 integrase inhibitors derived from quinolone antibiotics

AU - Sato, Motohide

AU - Motomura, Takahisa

AU - Aramaki, Hisateru

AU - Matsuda, Takashi

AU - Yamashita, Masaki

AU - Ito, Yoshiharu

AU - Kawakami, Hiroshi

AU - Matsuzaki, Yuji

AU - Watanabe, Wataru

AU - Yamataka, Kazunobu

AU - Ikeda, Satoru

AU - Kodama, Eiichi

AU - Matsuoka, Masao

AU - Shinkai, Hisashi

PY - 2006/3/5

Y1 - 2006/3/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33644863638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644863638&partnerID=8YFLogxK

U2 - 10.1021/jm0600139

DO - 10.1021/jm0600139

M3 - Article

C2 - 16509568

AN - SCOPUS:33644863638

SN - 0022-2623

VL - 49

SP - 1506

EP - 1508

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 5

ER -

Novel HIV-1 integrase inhibitors derived from quinolone antibiotics

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this