Inhibition of mycobacterial arylamine N-acetyltransferase contributes to anti-mycobacterial activity of Warburgia salutaris.
In this study, we show that extracts and a purified compound of Warburgia salutaris exhibit anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG Pasteur. The extracts did not inhibit growth of Escherichia coli and were not toxic to cultured mammalian macrophage cells at the concentrations at which anti-mycobacterial activity was observed. The extract and pure compound inhibited pure recombinant arylamine N-acetyltransferase (NAT), an enzyme involved in mycobacterial cell wall lipid synthesis. Moreover, neither extract nor pure compound inhibited growth of a strain of M. bovis BCG in which nat has been deleted suggesting that NAT may indeed be a target within the mycobacterial cell. The purified compound is a novel drimane sesquiterpenoid lactone, 11alpha-hydroxycinnamosmolide. These studies show that W. salutaris is a useful source of anti-tubercular compounds for further analysis and supports the hypothesis of a link between NAT inhibition and anti-mycobacterial activity.
Madikane
Vukani Eliya
VE
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. madikane@curie.uct.ac.za
Bhakta
Sanjib
S
Russell
Angela J
AJ
Campbell
William E
WE
Claridge
Timothy D W
TD
Elisha
B Gay
BG
Davies
Stephen G
SG
Smith
Peter
P
Sim
Edith
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008264:Macrophages; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009161:Mycobacterium / Q000187:drug effects* / Q000201:enzymology* / Q000648:ultrastructure; D009163:Mycobacterium bovis / Q000187:drug effects; D020102:Mycobacterium smegmatis / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; D012997:Solvents; D001191:Arylamine N-Acetyltransferase; D004121:Dimethyl Sulfoxide