Coordination chemistry based approach to lipophilic inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase

Lisheng Deng; Sandeep Sundriyal; Valentina Rubio Calva; Zheng-Zheng Shi; Yongcheng Song

doi:10.1021/jm9012592

Coordination chemistry based approach to lipophilic inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase

Lisheng Deng, Sandeep Sundriyal, Valentina Rubio Calva, Zheng-Zheng Shi, Yongcheng Song

Weill Cornell Medical College

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

61 Scopus citations

Abstract

1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-negative bacteria. A coordination chemistry and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC₅₀ of 1.4 μM. It exhibited a broad spectrum of activity against Gram-negative and -positive bacteria with minimal inhibition concentrations of 20-100 μM (or 3.7-19 μg/mL).

Original language	English (US)
Pages (from-to)	6539-6542
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	52
Issue number	21
DOIs	https://doi.org/10.1021/jm9012592
State	Published - Nov 12 2009

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

Access to Document

10.1021/jm9012592

Cite this

@article{20afe864737d4119b8ebdd90b5218972,

title = "Coordination chemistry based approach to lipophilic inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase",

abstract = "1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-negative bacteria. A coordination chemistry and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC50 of 1.4 μM. It exhibited a broad spectrum of activity against Gram-negative and -positive bacteria with minimal inhibition concentrations of 20-100 μM (or 3.7-19 μg/mL).",

author = "Lisheng Deng and Sandeep Sundriyal and {Rubio Calva}, Valentina and Zheng-Zheng Shi and Yongcheng Song",

year = "2009",

month = nov,

day = "12",

doi = "10.1021/jm9012592",

language = "English (US)",

volume = "52",

pages = "6539--6542",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "21",

}

TY - JOUR

T1 - Coordination chemistry based approach to lipophilic inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase

AU - Deng, Lisheng

AU - Sundriyal, Sandeep

AU - Rubio Calva, Valentina

AU - Shi, Zheng-Zheng

AU - Song, Yongcheng

PY - 2009/11/12

Y1 - 2009/11/12

N2 - 1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-negative bacteria. A coordination chemistry and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC50 of 1.4 μM. It exhibited a broad spectrum of activity against Gram-negative and -positive bacteria with minimal inhibition concentrations of 20-100 μM (or 3.7-19 μg/mL).

AB - 1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-negative bacteria. A coordination chemistry and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC50 of 1.4 μM. It exhibited a broad spectrum of activity against Gram-negative and -positive bacteria with minimal inhibition concentrations of 20-100 μM (or 3.7-19 μg/mL).

UR - http://www.scopus.com/inward/record.url?scp=71049170515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=71049170515&partnerID=8YFLogxK

U2 - 10.1021/jm9012592

DO - 10.1021/jm9012592

M3 - Article

C2 - 19888756

AN - SCOPUS:71049170515

SN - 0022-2623

VL - 52

SP - 6539

EP - 6542

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 21

ER -

Coordination chemistry based approach to lipophilic inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this