Back to Search
Start Over
Supramolecular strategy for reducing the cardiotoxicity of bedaquiline without compromising its antimycobacterial efficacy.
- Source :
-
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2018 Sep; Vol. 119, pp. 425-429. Date of Electronic Publication: 2017 Dec 16. - Publication Year :
- 2018
-
Abstract
- Bedaquiline (BDQ) is a newly approved anti-tuberculosis drug in treating multidrug-resistant tuberculosis. However, it has very poor aqueous solubility and several case reports have proposed that BDQ has potential risk of cardiotoxicity to patients. In this present study, we have explored into employing host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and BDQ aiming to improve the solubility and reduce the inherent cardiotoxicity of BDQ. HPLC-UV test on the solubility of BDQ in the absence and in the presence of increasing concentrations of CB[7] suggested a host-dependent guest-solubility enhancements. Cardiovascular studies using an in vivo zebrafish model demonstrated that the cardiotoxicity of BDQ was indeed alleviated upon its complexations by the synthetic receptor. Furthermore, our in vitro antibacterial studies suggested that CB[7] formulated BDQ preserved its antimycobacterial efficacy against Mycobacterium smegmatis. Therefore, CB[7] may become a suitable pharmaceutical excipient in formulating BDQ for improving its physiochemical properties (such as solubility), and for alleviating its side effects (such as cardiotoxicity), while the antimycobacterial efficacy of BDQ may be well maintained.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Animals, Genetically Modified
Bridged-Ring Compounds pharmacology
Chromatography, High Pressure Liquid
Imidazoles pharmacology
Microbial Sensitivity Tests
Mycobacterium smegmatis drug effects
Solubility
Zebrafish embryology
Antitubercular Agents therapeutic use
Diarylquinolines toxicity
Heart drug effects
Tuberculosis, Multidrug-Resistant drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6351
- Volume :
- 119
- Database :
- MEDLINE
- Journal :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
- Publication Type :
- Academic Journal
- Accession number :
- 29258954
- Full Text :
- https://doi.org/10.1016/j.fct.2017.12.022