Abstract
Lipophilic fractions of stem extracts from Exocarpos latifolius, native to Papua New Guinea, showed significant activity against Mycobacterium tuberculosis H37Ra. Bioactivity-guided fractionation yielded exocarpic acid (E-octadeca-13-ene-9,11-diynoic-acid) as the major active component. Several new exocarpic acid analogs were also shown to be active. Exocarpic acid has previously been reported active against gram-positive, but not gram-negative bacteria. Work presented here demonstrates the selective activity of exocarpic acid against Mycobacterium tuberculosis H37Ra.
Key words
Mycobacterium tuberculosis
- Exocarpos latifolius - Santalaceae - exocarpic acid - polyacetylenic fatty acids
References
-
1 International Cooperative Biodiversity Groups (ICBG). Available at http://www.fic.nih.gov/programs/research_grants/icbg/. Accessed October 15, 2008
-
2 TB Country Profile Papua New Guinea. Available at http://www.who.int/globalatlas/predefinedReports/TB/PDF_Files/png.pdf. Accessed October 15, 2008
-
3
El-Jaber N A, Estevez-Braun A G, Munoz-Munoz R O, Rodrıguez-Alfonso A, Murguia J R.
Acetylenic acids from the aerial parts of Nanodea muscos.
J Nat Prod.
2003;
66
722-724
-
4
Naidoo L AC, Drewes S E, Van Staden J, Hutchings A.
Exocarpic acid and other compounds from tubers and inflorescences of Sarcophyte sanguinea.
Phytochemistry.
1992;
31
3929-3931
-
5
Li X-C, Jacob M R, Khan S I, Ashfaq M K, Babu K S, Agarwal A K, El Sohly H N, Manly S P, Clark A M.
Potent in vitro antifungal activities of naturally occurring acetylenic acids.
Antimicrob Agents Chemother.
2008;
52
2442-2448
-
6
Zgoda J R, Freyer A J, Killmer L B, Porter J R.
Polyacetylene carboxylic acids from Mitrephora celebica.
J Nat Prod.
2001;
64
1348-1349
-
7
Kobaisy M, Abramowski Z, Lermer L, Saxena G, Hancock R EW, Towers G HN.
Antimycobacterial polyynes of Devil's club (Oplopanax horridus), a North American native medicinal plant.
J Nat Prod.
1997;
60
1210-1213
-
8
Naidoo L AC, Drewes S E, Drewes F E, Van Staden J, Aken M E.
When is a parasite no longer a parasite? The case of Sarcophyte sanguinea and exocarpic acid.
South African J Sci.
1994;
90
359-361
-
9
Franzblau S G, Witzig R S, McLaughlin J C, Torres P, Madico G, Hernandez A, Degnan M T, Cook M B, Quenzer V K, Ferguson R M, Gilman R H.
Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate alamar blue assay.
J Clin Microbiol.
1998;
36
362-366
-
10
Foongladda S, Roengsanthia D, Arjrattanakool W, Chuchottaworn C, Chaiprasert A, Franzblau S G.
Rapid and simple MTT method for rifampicin and isoniazid susceptibility testing of Mycobacterium tuberculosis.
Int J Tuberc Lung Dis.
2002;
6
1118-1122
-
11 Ferraro M J, Craig W A, Dudley M N, Eliopoulos G M, Hecht D W, Hindler J, Reller L B, Shelodon A T, Swenson J M, Tenover F C, Testa R T, Weinstein M P, Wikler M A. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 5th edition. Wayne; NCCLS 2000
-
12
Amakura Y, Kondo K, Akiyama H, Ito H, Hatano T, Yoshida T, Tamio M.
Characteristic long-chain fatty acid of Pleurocybella porrigens.
J Food Hyg Soc Jap.
2006;
47
178-181
-
13
Badami R C, Gunstone F D.
Vegetable oils. XIII – The component acids of isano (boleko) oil.
J Sci Food Agric.
1963;
14
863-866
-
14 The Tuberculosis Antimicrobial Acquisition and Coordinating Facility. Available at http://www.taacf.org. Accessed October 15, 2008
-
15
Collins L A, Franzblau S G.
Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium.
Antimicrob Agents Chemother.
1997;
41
1004-1009
-
16
Cho H S, Warit S, Wan B, Hwang C H, Pauli G E, Franzblau S G.
Low oxygen recovery assay (LORA) for high throughput screening of compounds against non-replicating Mycobacterium tuberculosis.
Antimicrob Agents Chemother.
2007;
51
1380-1385
-
17
Morbidoni C, Vilchèze L, Kremer R, Bittman J, Sacchettini W, Jacobs J R.
Dual inhibition of mycobacterial fatty acid biosynthesis and degradation by 2-alkynoic acids.
Chem Biol.
2006;
13
297-307
-
18
Wu L, Liu Z, Li D.
Oct-2-yn-4-enoyl-CoA as a multifunctional enzyme inhibitor in fatty acid oxidation.
Org Lett.
2008;
10
2235-2238
-
19
Ondeyka J, Zink D, Young K, Painter R, Kodali S, Galgoci A, Collado J, Tormo J R, Basilio A, Vicente F, Wang J, Singh S B.
Discovery of bacterial fatty acid synthase inhibitors from a Phoma species as antimicrobial agents using a new antisense-based strategy.
J Nat Prod.
2006;
69
377-380
Prof. Dr. Louis R. Barrows
Department of Pharmacology and Toxicology
University of Utah
30 S., 2000 E.
Salt Lake City, UT 84112
USA
Telefon: + 1 80 15 81 45 47
eMail: louis.barrows@pharm.utah.edu