Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 58, Issue 15, Pages 5842-5853Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b00428
Keywords
-
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT), Portugal [PTDC/BIA-MIC/121859/2010]
- FCT, Portugal [PTDC/BIA-MIC/121859/2010 (BI), SFRH/BPD/97508/2013]
- Fundação para a Ciência e a Tecnologia [PTDC/BIA-MIC/121859/2010] Funding Source: FCT
Ask authors/readers for more resources
Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the leading infectious diseases globally. Therefore, novel approaches are needed to face this disease. Efflux pumps are known to contribute to the emergence of M tuberculosis drug resistance. Thioridazine has shown good anti-TB properties both in vitro and in vivo, likely due to its capacity to inhibit efflux mechanisms. Here we report the design and synthesis of a number of putative efflux inhibitors inspired by the structure of thioridazine. Compounds were evaluated for their in vitro and ex vivo activity against M. tuberculosis H37Rv. Compared to the parent molecule, some of the compounds synthesized showed higher efflux inhibitory capacity, less cytotoxicity, and a remarkable synergistic effect with anti-TB drugs both in vitro and in human macrophages, demonstrating their potential to be used as coadjuvants for the treatment of tuberculosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available