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Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy
Li S.1; Chan J.Y.-W.1; Li Y.2; Bardelang D.3; Zheng J.2; Yew W.W.4; Chan D.P.-C.4; Lee S.M.Y.1; Wang R.1
2016
Source PublicationOrganic and Biomolecular Chemistry
ISSN14770520
Volume14Issue:31Pages:7563-7569
Abstract

Cucurbit[7]uril (CB[7]) has recently attracted increasing attention in pharmaceutical sciences due to its great potential in improving the physicochemical properties and bioactivity of drug molecules. Herein, we have investigated the influence of CB[7]'s complexation on the solubility, antimycobacterial activity, and cardiotoxicity of a model anti-tuberculosis drug, clofazimine (CFZ), that has poor water-solubility and inherent cardiotoxicity. In our study, CFZ was found to be complexed by CB[7], in a 1:1 binding mode with a relatively strong binding affinity (in the order of magnitude of 10-10 M), as determined by the phase solubility method via HPLC-UV analysis and H NMR titration, as well as UV-visible spectroscopic titration, and further confirmed by electrospray ionization mass spectrometry (ESI-MS). Upon complexation, the solubility of virtually insoluble CFZ was significantly increased, reaching a concentration of up to approximately 0.53-fold of the maximum solubility of CB[7]. The inherent cardiotoxicity of CFZ was dramatically reduced to almost nil in the presence of CB[7]. Importantly, on the other hand, such a supramolecular complexation of the drug did not compromise its therapeutic efficacy, as shown by the antimycobacterial activities examined against Mycobacterium smegmatis, demonstrating the significant potential of CB[7] as a functional pharmaceutical excipient.

DOIhttp://doi.org/10.1039/c6ob01060a
URLView the original
Indexed BySCI
Language英语
WOS Research AreaChemistry
WOS SubjectChemistry, Organic
WOS IDWOS:000381419700019
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Cited Times [WOS]:33   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Faculty of Health Sciences
Corresponding AuthorWang R.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
2.Faculty of Health Sciences, University of Macau, Taipa, China
3.Aix-Marseille Université, CNRS, Institut de Chimie Radicalaire, UMR 7273, 13013 Marseille, France
4.Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Li S.,Chan J.Y.-W.,Li Y.,et al. Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy[J]. Organic and Biomolecular Chemistry,2016,14(31):7563-7569.
APA Li S..,Chan J.Y.-W..,Li Y..,Bardelang D..,Zheng J..,...&Wang R..(2016).Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy.Organic and Biomolecular Chemistry,14(31),7563-7569.
MLA Li S.,et al."Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy".Organic and Biomolecular Chemistry 14.31(2016):7563-7569.
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