Isolation and Identification of a Potent Antimalarial and Antibacterial Polyacetylene from Bidens pilosa

Abstract

Diseases caused by malaria parasites and pathogenic bacteria were thought to be on the brink of eradication in the 1950–1960s, but they have once again become a serious threat to mankind as a result of the appearance of multidrug resistant strains. The spread of these multidrug resistant organisms has prompted a worldwide search for new classes of effective antimalarial and antibacterial drugs. Natural products have been recognized as highly important candidates for this purpose. Our attention has focused on the herbal plant Bidens pilosa, a weed common throughout the world, as one of the target plants in the search for new active compounds, owing to its empirical use in the treatment of infectious diseases and to pharmaco-chemical studies of its crude extract. We report the isolation of two new compounds of B. pilosa, the linear polyacetylenic diol 1 and its glucoside 2 which have previously been isolated from different plants. Compound 1 exhibited highly potent antimalarial and antibacterial properties in vitro as well as potent antimalarial activity by way of intravenous injection in vivo, thereby representing a promising new class of drugs potentially effective in the treatment of malarial and bacterial diseases. We suspect that discovery of these compounds in B. pilosa in appreciable quantity is because the Fijian tradition of using the fresh plant for extraction rather than the Asian tradition of using dried plants (1 is unstable in the dried state) was followed.

Key words

Bidens pilosa - Compositae - polyacetylenes - antimalarial activity - antibacterial activity

References

• 1 Bulter D. Time to put malaria control on the global agenda.  Nature. 1997;  386 535-536
• 2 Thayer N M. Fighting malaria.  Chem Eng News. 2005;  69-82
• 3 Butler M S, Buss S D. Natural products – the future scaffolds for novel antibiotics?.  Biochem Pharmacol. 2006;  71 919-929
• 4 Nosten F, Ter Kuile F, Chongsuhphajaisiddhi T, Luxemburger D, Webster H K, Edstern M, Phaipun L, Thew K L, White N J. Mefloqune-resistant falciparum malaria on the Thai-Burmese border.  Lancet. 1991;  337 1140-1143
• 5 Kremsner P G, Kishna S. Antimalarial combinations.  Lancet. 2004;  364 282-294
• 6 Klayman D L. Qingghaosu (artemicinin): an antimalarial drug from China.  Science. 1985;  228 1049-1055
• 7 Brandão M GL, Krettli A U, Soares L SR, Nery C GC, Marinuzzi H C. Antimalarial activity of extracts and fractions from Bidens pilosa and other Bidens species (Asteraceae) correlated with the presence of acetylene and flavonoids compounds.  J Ethnopharmacol. 1997;  57 131-138
• 8 Oliveira F Q, Andrade-Neto V, Krettli A U, Brandão M GL. New evidences of antimalarial activity of Bidens pilosa roots extract correlated with polyacetylene and flavonoids.  J Ethnopharmacol. 2004;  93 39-42
• 9 Andrade-Neto V F, Brandão M GL, Oliveira F Q, Casali V WD, Njaine B, Zalis M G, Luciana A O, Krettli A U. Antimalarial activity of Bidens pilosa L., (Asteraceae) ethanol extracts from wild plants collected in various localities or plants cultivated in humus soil.  Phytother Res. 2004;  18 634-639
• 10 Wat C K, Johns T, Towers N GH. Phototoxic and antibiotic activities of plants of the Asteraceae used in folk medicine.  J Ethnopharmacol. 1980;  2 279-290
• 11 Wat C K, Biswas R K, Graham E A, Bohm L, Towers G HN. Ultraviolet-mediated cyctotoxic activity of phenylheptatriyne from Bidens pilosa L.  J Nat Prod. 1979;  42 103-111
• 12 Ubillass R P, Mendez C D, Jolad S D, Luo J, Stiven R, Carlson T J, Fort D M. Antihyperglycemic acetylenic glucosides from Bidens pilosa.  Planta Med. 2000;  66 82-83
• 13 Tan P V, Dimo T, Dongo E. Effects of methanol, cyclohexane and methylene chloride extracts of Bidens pilosa on various gastric ulcer models in rats.  J Ethnopharmacol. 2000;  73 415-421
• 14 Dimo T, Azay J, Tan P V, Pellecuer J, Cros G, Bopelet M, Serrano J J. Effects of the aqueous and methylene chloride extracts of Bidens pilosa leaf on fructose-hypertensive rats.  J Ethnopharmacol. 2001;  76 215-221
• 15 Christensen L P, Lam J. Acetylenes and related compounds in Heliantheae.  Phytochemistry. 1991;  30 11-49
• 16 Alvarez L, Marquina S, Villarreal M L, Alonso D, Aranda W, Delagado G. Bioactive polyacetylenes from Bidens pilosa.  Planta Med. 1996;  62 355-357
• 17 Ubillas R P, Mendez C D, Jolad S D, Luo J, King S R, Carlson T J, Fort D M. Antihyperglycemic acetylenic glucosides from Bidens pilosa.  Planta Med. 2000;  66 82-83
• 18 Hoffmann B, Hölzl J. New chalcone from Bidens pilosa.  Planta Med. 1988;  54 52-54
• 19 Zulueta M CA, Toda M, Ragasa C Y. Diterpene from Bidens pilosa.  Phytochemistry. 1995;  38 1449-1450
• 20 Bohlmann F, Arndt C, Kleine K M, Wotchokowsky M. Neue Inhaltstoffe aus Bidens-Arten.  Chem Berlin. 1965;  98 1228-1232
• 21 Rücker G, Kehrbaum S, Sakulas H, Lawong B, Goeltenboth F. Acetylenic glucosides from Microglossa pyrifolia.  Planta Med. 1992;  58 266-269
• 22 Mori K, Otsuka T. Synthesis of the enantiomers of 5-hexadecanolide, the pheromone of the queen of the oriental hornet, Vespa orientalis, employing enzymatic resolution of (±)-2-aminotridecanoic acid as the key-step.  Tetrahedron. 1985;  41 547-551
• 23 Geraghty P. Wai Vaka Viti (Herbal Medicine in Fiji). Fiji; Department of Fijian Culture, Government of Fiji 1998
• 24 Cambie R C, Ash J. Fijian medicinal plants. Australia; CSIRO 1994
• 25 National Committee for Clinical Laboratory Standards .Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 5th edition. Approved Standard M7-M4. Wayne, PA; National Committee for Clinical Laboratory Standards 2001
• 26 Nagel R L, Raventos H B, Wittner M. Effect of sodium cyanate on Plasmodium falciparium in vitro.  J Parasitol. 1980;  66 483-489
• 27 Peters W. The problem of drug resistance in malaria.  Parasitology. 1985;  90 705-715