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 | |
| Publication status | Published - 2011 Mar 1 |
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All Science Journal Classification (ASJC) codes
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
- Biochemistry
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Synthesis and antitubercular activity of monocyclic nitroimidazoles : Insights from econazole. / Lee, Sang Ho; Kim, Suhyun; Yun, Min Han; Lee, Yong Sup; Cho, Sangnae; Oh, Taegwon; Kim, Pilho.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 5, 01.03.2011, p. 1515-1518.Research output: Contribution to journal › Article
TY - JOUR
T1 - Synthesis and antitubercular activity of monocyclic nitroimidazoles
T2 - Insights from econazole
AU - Lee, Sang Ho
AU - Kim, Suhyun
AU - Yun, Min Han
AU - Lee, Yong Sup
AU - Cho, Sangnae
AU - Oh, Taegwon
AU - Kim, Pilho
PY - 2011/3/1
Y1 - 2011/3/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=79951723342&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2010.12.128
DO - 10.1016/j.bmcl.2010.12.128
M3 - Article
VL - 21
SP - 1515
EP - 1518
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 5
ER -