Pentacyclo-undecane derived cyclic tetra-amines: synthesis and evaluation as potent anti-tuberculosis agents.

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.

• 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)

Chemical References

• Alkanes
• Antitubercular Agents
• undecane

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