Synthesis and antitubercular activity of monocyclic nitroimidazoles: Insights from econazole

Sang Ho Lee; Suhyun Kim; Min Han Yun; Yong Sup Lee; Sang Nae Cho; Taegwon Oh; Pilho Kim

doi:10.1016/j.bmcl.2010.12.128

Synthesis and antitubercular activity of monocyclic nitroimidazoles: Insights from econazole

Sang Ho Lee, Suhyun Kim, Min Han Yun, Yong Sup Lee, Sang Nae Cho, Taegwon Oh, Pilho Kim

Department of Microbiology

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

28 Citations (Scopus)

Abstract

We have designed and synthesized econazole-derived nitroimidazoles to investigate the antitubercular activity of the nitroimidazole compounds. The introduction of a nitro group at the 4-position of the imidazole on econazole abolished the antitubercular activity. However, alcoholic nitroimidazoles 4 and 6 compounds were active against Mycobacterium tuberculosis (Mtb). While the MIC value of econazole was 16 μg/mL, the MIC of 6a and 6f turned out to be 0.5 μg/mL. In particular, the activity of 6f against non-replicating Mtb was as good as PA-824, which is currently in clinical phase II studies as an antitubercular agent. Overall, alcohol compounds 4 and 6 tend to be more active than ether compounds 5 and 7.

Original language	English
Pages (from-to)	1515-1518
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2010.12.128
Publication status	Published - 2011 Mar 1

Bibliographical note

Funding Information:
This research was supported in part by Korea Research Institute of Chemical Technology (KRICT) and by the International Research & Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) of Korea (Grant No.: K20501000001-09E0100-00110, FY 2009 ).

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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title = "Synthesis and antitubercular activity of monocyclic nitroimidazoles: Insights from econazole",

abstract = "We have designed and synthesized econazole-derived nitroimidazoles to investigate the antitubercular activity of the nitroimidazole compounds. The introduction of a nitro group at the 4-position of the imidazole on econazole abolished the antitubercular activity. However, alcoholic nitroimidazoles 4 and 6 compounds were active against Mycobacterium tuberculosis (Mtb). While the MIC value of econazole was 16 μg/mL, the MIC of 6a and 6f turned out to be 0.5 μg/mL. In particular, the activity of 6f against non-replicating Mtb was as good as PA-824, which is currently in clinical phase II studies as an antitubercular agent. Overall, alcohol compounds 4 and 6 tend to be more active than ether compounds 5 and 7.",

author = "Lee, {Sang Ho} and Suhyun Kim and Yun, {Min Han} and Lee, {Yong Sup} and Cho, {Sang Nae} and Taegwon Oh and Pilho Kim",

note = "Funding Information: This research was supported in part by Korea Research Institute of Chemical Technology (KRICT) and by the International Research & Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) of Korea (Grant No.: K20501000001-09E0100-00110, FY 2009 ). ",

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AU - Lee, Sang Ho

AU - Kim, Suhyun

AU - Yun, Min Han

AU - Lee, Yong Sup

AU - Cho, Sang Nae

AU - Oh, Taegwon

AU - Kim, Pilho

N1 - Funding Information: This research was supported in part by Korea Research Institute of Chemical Technology (KRICT) and by the International Research & Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) of Korea (Grant No.: K20501000001-09E0100-00110, FY 2009 ).

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