Abstract |
As part of an ongoing effort to develop highly potent anti-tuberculosis agents, fourteen pentacyclo- undecane (PCU) tetra- amine compounds were synthesized and screened for their in vitro anti-mycobacterial activity against two TB strains, H37Rv and XDR 194 [an extensively drug-resistant strain of tuberculosis]. Using the broth macrodilution method, nitrofuranylamide based compounds (6a and 6b) showed almost similar activities against the H37Rv strain of Mycobacterium tuberculosis when compared with the control drug, ethambutol. N-Geranyl piperazine PCU (8a) and trans-trans farnesyl piperazine PCU (8b) were 3.2 and 3.7 times more potent than commercially available ethambutol. Both isoprenyl PCU tetra- amine derivatives and N-decyl piperazine PCU (9a) were highly active against the XDR 194 strain of tuberculosis with MICs in the range of 0.63-3.02 microM. Cytotoxicities (IC(50)) of isoprenyl based compounds (8a, 8b) and compound 9a were tested on a mammalian cell line [MDBK (Madin Darby bovine kidney epithelium)] with values of 30, 24 and 25 microM respectively.
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Authors | Oluseye K Onajole, Karnishree Govender, Patrick Govender, Paul D van Helden, Hendrik G Kruger, Glenn E M Maguire, Karen Muthusamy, Manormoney Pillay, Ian Wiid, Thavendran Govender |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 44
Issue 11
Pg. 4297-305
(Nov 2009)
ISSN: 1768-3254 [Electronic] France |
PMID | 19679378
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Alkanes
- Antitubercular Agents
- undecane
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Topics |
- Alkanes
(chemical synthesis, chemistry, pharmacology)
- Animals
- Antitubercular Agents
(chemical synthesis, chemistry, pharmacology)
- Cattle
- Cell Line
- Cell Survival
- Inhibitory Concentration 50
- Microbial Sensitivity Tests
- Molecular Structure
- Mycobacterium tuberculosis
(drug effects)
- Prenylation
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