- Title
- Quinolone-isoniazid hybrids: Synthesis and preliminary in vitro cytotoxicity and anti-tuberculosis evaluation
- Creator
- Beteck, Richard M, Seldon, Ronnett, Khanye, Setshaba D, Legoabe, Lesetja J, Hoppe, Heinrich C, Laming, Dustin, Jordaan, Audrey, Warner, Digby F
- Date
- 2019
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/123151
- Identifier
- vital:35410
- Identifier
- https://doi.org/10.1039/C8MD00480C
- 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, pdf
- Language
- English
- Relation
- MedChemComm, Beteck, R.M., Seldon, R., Jordaan, A., Warner, D.F., Hoppe, H.C., Laming, D., Legoabe, L.J. and Khanye, S.D., 2019. Quinolone-isoniazid hybrids: Synthesis and preliminary in vitro cytotoxicity and anti-tuberculosis evaluation. Medchemcomm, 10(2), pp.326-331., MedChemComm number 10 326 331 2019 2040-2511
- Rights
- South African Journal of Chemistry
- Rights
- Use of this resource is governed by the terms and conditions of the Royal Society of Chemistry Terms and Conditions Statemen (http://www.rsc.org/help-legal/)
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Khanye, David Setshaba (Associate Prof)
RU Centre for Chemico- and Biomedicinal Research (CCBR)
Hoppe, Heinrich C (Prof)
RU Department of Pharmacy
SDG 03. Good Health and Well-Being
RU Department of Biochemistry, Microbiology and Bioinformatics
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Quinolone.xml | 6 KB | XML Document | View Details Download | ||
| View Details Download | SOURCE2 | Adobe Acrobat PDF | 2 MB | Adobe Acrobat PDF | View Details Download |