- Title
- A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties
- Creator
- Odame, Felix
- Creator
- Betz, Richard
- Creator
- Hosten, Eric C
- Creator
- Krause, Jason
- Creator
- Isaacs, Michelle
- Creator
- Hoppe, Heinrich C
- Creator
- Khanye, Setshaba D
- Creator
- Sayed, Yasien
- Creator
- Frost, P Carminita
- Creator
- Lobb, Kevin A
- Creator
- Tshentu, Zenixole
- Date Issued
- 2018
- Date
- 2018
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/123189
- Identifier
- vital:35413
- Identifier
- https://doi.org/10.1002/slct.201802930
- Description
- Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing an INH moiety attached via a hydrazide–hydrazone bond were synthesised and evaluated against Mycobacterium tuberculosis H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines. These compounds showed significant activity (MIC90) against MTB in the range of 0.2–8 μM without any cytotoxic effects. Compounds 10 (MIC90; 0.9 μM), 11 (MIC90; 0.2 μM), 12 (MIC90; 0.8 μM) and compound 15 (MIC90; 0.8 μM), the most active compounds in this series, demonstrate activities on par with INH and superior to those reported for the fluoroquinolones. The SAR analysis suggests that the nature of substituents at positions −1 and −3 of the quinolone nucleus influences anti-MTB activity. Aqueous solubility evaluation and in vitro metabolic stability of compound 12 highlights favourable drug-like properties for this compound class.
- Format
- 6 pages
- Format
- Language
- English
- Relation
- ChemistrySelect
- Relation
- Odame, F., Betz, R., Hosten, E.C., Krause, J., Isaacs, M., Hoppe, H.C., Khanye, S.D., Sayed, Y., Frost, P.C., Lobb, K.A. and Tshentu, Z.R., 2018. A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties. ChemistrySelect, 3(48), pp.13613-13618.
- Relation
- ChemistrySelect number 3 13613 13618 2018 2365-6549
- Rights
- South African Journal of Chemistry
- Rights
- Use of this resource is governed by the terms and conditions of the Wiley Online Library Terms of Use Statement (https://onlinelibrary.wiley.com/terms-and-conditions)
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Collections
Tshentu, Zenixole Richman (Dr)
RU Department of Biochemistry, Microbiology and Biotechnology
Isaacs, Michelle (Mrs)
Hoppe, Heinrich C (Prof)
RU Department of Pharmacy
Khanye, David Setshaba (Associate Prof)
RU Department of Chemistry
Lobb, Kevin Allan (Assoc Prof)
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