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.
Bibliographical noteFunding 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
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry