- 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 R
- 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)
- Hits: 3164
- Visitors: 3293
- Downloads: 165
Collections
Tshentu, Zenixole Richman (Dr)
Khanye, David Setshaba (Associate Prof)
Lobb, Kevin Allan (Assoc Prof)
Hoppe, Heinrich C (Prof)
Isaacs, Michelle (Mrs)
RU Department of Chemistry
RU Department of Pharmacy
RU Department of Biochemistry, Microbiology and Bioinformatics
SDG 03. Good Health and Well-Being
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Done -A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties.pdf | 6 MB | Adobe Acrobat PDF | View Details Download |