Abstract.
Natural products are not only the basis for traditional or ethnic medicine. Only recently, they have provided highly successful new drugs such as Artemisinin. Furthermore, screening natural products found in all sorts of environments such as the deep sea, rain forests and hot springs, and produced by all sorts of organisms ranging from bacteria, fungi and plants to protozoa, sponges and invertebrates, is a highly competitive field where all of the major pharmaceutical companies are encountered. Already, many new natural product groups have revealed antiparasitic properties of surprising efficacy and selectivity, as will be shown in this review for plant-derived alkaloids, terpenes and phenolics. Many novel lead structures, however, have severe chemico-physical drawbacks such as poor solubility. Here, innovative drug formulations and carrier systems might help, as discussed by the authors in another article of this series.
Similar content being viewed by others
References
Akendengue B, Ngou-Milama E, Laurens A, Hocquemiller R (1999) Recent advances in the fight against leishmaniasis with natural products. Parasite 6:3–8
Angerhofer CK, Pezzuto JM, König GM, Wright AD, Sticher O (1992) Antimalarial activity of sesquiterpenes from the marine sponge Acanthella klethra. J Nat Prod 55:1787–1789
Angerhofer CK, Guinaudeau H, Wongpanich V, Pezzuto JM, Cordell GA (1999) Antiplasmodial and cytotoxic activity of natural bisbenzylisoquinoline alkaloids. J Nat Prod 62:59–66
Bastos JK, Albuquerque S, Silva ML (1999) Evaluation of the trypanocidal activity of lignans isolated from the leaves of Zanthoxylum naranjillo. Planta Med 65:541–544
Barata LE, Santos LS, Ferri PH, Phillipson JD, Paine A, Croft SL (2000) Anti-leishmanial activity of neolignans from Virola species and synthetic analogues. Phytochemistry 55:589–595
Bezabih M, Abegaz BM, Dufall K, Croft SL, Skinner-Adams T, Davis TM (2001) Antiplasmodial and antioxidant isofuranonaphthoquinones from the roots of Bulbine capitata. Planta Med 67:340–374
Chen M, Christensen SB, Blom J, Lemmich E, Nadelmann L, Fich K, Theander TG, Kharazami A (1993) Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania. Antimicrob Agents Chemother 37:2550–2556
Chen M, Theander TG, Christensen SB, Hviid L, Zhai L, Kharazami A (1994a) Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani. Antimicrob Agents Chemother 38:1339–1344
Chen M, Theander TG, Christensen SB, Hviid L, Zhai L, Kharazami A (1994b) Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection. Antimicrob Agents Chemother 38:1470–1475
El-On J, Jacobs GP, Weinrauch L (1988) Topical chemotherapy of cutaneous leishmaniasis. Parasit Today 4:76–81
Elford BC, Roberts MF, Phillipson JD, Wilson RJ (1987) Potentiation of the antimalarial activity of qinghaosu by methoxylated flavones. Trans R Soc Trop Med Hyg 81:434–436
Fournet A, Barrios AA, Munoz V, Hocquemiller R, Cave A (1992) Effect of natural naphthoquinones in BALB/c mice infected with Leishmania amazonensis and L. venezuelensis. Trop Med Parasitol 43:219–222
Fournet A, Barrios AA, Munoz V, Hocquemiller R, Cave A, Bruneton J (1993a) 2-substituted quinoline alkaloids as potential antileishmanial drugs. Antimicrob Agent Chemother 37:859–863
Fournet A, Hocquemiller R, Roblot F, Cave A, Richomme P, Bruneton J (1993b) Effects of some bisbenzylisoquinoline alkaloids on American Leishmania sp. in BALB/c mice. Phytother Res 7:281–284
Francois G, Timperman G, Elling W, Assi LA, Holenz J, Bringmann G (1997a) Naphthylisoquinoline alkaloids from Triphyophyllum peltatum, Ancistrocladus abbreviatus and Ancistrocladus barteri against Plasmodium berghei (Anka strain) in vivo. J Ethnopharmacol 46:115–120
Francois G, Timperman G, Elling W, Assi LA, Holenz J, Bringmann G (1997b) Naphthylisoquinoline alkaloids against malaria: evaluation of the curative potentials of dioncophylline C and dioncopeltine A against P. berghei in vivo. Antimicrob Agents Chemother 41:2533–2539
Gale M Jr, Carter V, Parsons M (1994) Cell cycle-specific induction of an 89 kDa serine/threonine protein kinase activity in Trypanosoma brucei. J Cell Sci 107:1825–1832
Gantier JC, Fournet A, Munos HM, Hocquemiller R (1996) The effect of some 2-substitutes quinolines isolated from Galipea longiflora on Plasmodium vinckei petteri infected mice. Planta Med 62:285–286
Grellier P, Ramiaramanana L, Millerioux V, Deharo E, Schrevel J, Frappier F, Trigalo F, Bodo B, Pousset J-L (1996) Antimalarial activity of cryptolepine and isocryptolepine, alkaloids isolated from Cryptolepsis sanguinolenta. Phytother Res 10:317–321
Hallock YF, Cardellina JHII, Schaffer M, Bringmann G, Francois G, Boyd MR (1998) Korundamine A, a novel HIV-inhibitory and antimalarial "hybrid" naphthylisoquinoline alkaloid heterodimer from Ancistrocladus korupensis. Bioorg Med Chem Lett 8:1729
Hazra B, Gosh R, Banerjee A, Kirby GC, Warhust DC, Phillipson JD (1995) In vitro antiplasmodial effects of diospyrin, a plant-derived naphthoquinoid, and a novel series of derivatives. Phytother Res 9:72–74
Hocquemiller R, Cortes D, Arango GJ, Myint SH, Cavé A (1991) Isolation and synthesis of espintanol, a new antiparasitic monoterpene. J Nat Prod 54:445–452
Holzgrabe U, Bechthold A (1999) Paradigmenwechsel in der Entwicklung antiinfektiver Chemotherapeutika. Chemother J 8:69–78
Kannan R, Sahal D, Chauhan VS (2002) Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization. Chem Biol 9:321–332
Kayser O, Kiderlen AF, Folkens U, Kolodziej H (1999) Antileishmia activity of aurones. Planta Med 65:315–319
Kayser O, Kiderlen AF, Laatsch H, Croft SL (2000) In vitro leishmanicidal activity of monomeric and dimeric naphthoquinones. Acta Trop 77:307–314
Kayser O, Brun R, Kiderlen AF (2001a) In vitro activity of aurones against Plasmodium falciparum strains NF1 and K54. Planta Med 67:718–721
Kayser O, Waters WR, Upton S, Keithly JS (2001b) Evaluation of in vitro and in vivo activity of aurones and related compounds against Cryptosporidium parvum. Planta Med 67:722–725
Kayser O, Kiderlen AF, Laatsch H (2001c) Verwendung von Naphthindazol-4,9-chinonen als Antiparasitika. 31st October 2001, patent number: DE 100 20 812.6
Kayser O, Kiderlen A, Croft SL (2002) Natural Products as potential antiparasitic drugs. Studies in Natural Product Research, Atta-Ur-Rahman (eds.), 26:779–848
Khan AA, Nasr M, Araujo FG (1998) Two 2-hydroxy-3-alkyl-1,4-naphthoquinones with in vitro and in vivo activities against Toxoplasma gondii. Antimicrob Agents Chemother 42:2284–2289
Kraft C, Jenett-Siems K, Köhler I, Tofern-Reblin B, Siems K, Bienzle U, Eich E (2002) Antiplasmodial activity of sesquilignans and sesquineolignans from Bonamia spectabilis. Phytochemistry 60:167–173
König GM, Wright AD (1996) Marine natural products research: current directions and future potential. Planta Med 62:193–211
Kirby GC, Paine A, Warhust DC, Noamese BK, Phillipson JD (1995) In vitro and in vivo antimalarial activity of cryptolepine, a plant-derivative indolquinoline. Phytother Res 9:359–363
Li R, Kenyon GL, Cohen FE, Chen X, Gong B, Dominguez JN, Davidson E, Kurzban G, Miller GE, Nuzum EO, Rosenthal PJ, McKerrow JH (1995) In vitro antimalarial activity of chalcones and their derivatives. J Med Chem 38:5031–5037
Likhitwitayawuid K, Kaewamatawong R, Ruangrungsi N, Krungkrai J (1998) Antimalarial naphthoquinones from Nepenthes thorelii. Planta Med 64:237–241
Lopes JN, Cruz FS, Docampo R, Vasconcellos ME, Sampaio MC, Pinto AV, Gilbert B (1978) In vitro and in vivo evaluation of the toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Trypanosoma cruzi. Ann Trop Med Parasitol 72:523–531
Lopes NP, Chicaro P, Kato MJ, Albuquerque S, Yoshida M (1998) Flavonoids and lignans from Virola surinamensis twigs and their in vitro activity against Trypanosoma cruzi. Planta Med 64:667–668
MacKinnon S, Durst T, Arnason JT, Angerhofer C, Pezzuto J, Sanchez-Vindas PE, Poveda LJ, Gbeassor M (1997) Antimalarial activity of tropical Meliaceae extracts and gedunin derivatives. J Nat Prod 60:336–341
Nosten F, Brasseur P (2002) Combination therapy for malaria: the way forward? Drugs 62:1315–1329
Oketch-Rabah HA, Dossaji SF, Christensen SB, Frydenvang K, Lemmich E, Cornett C, Olsen CE, Chen M, Kharazmi A, Theander T (1997) Antiprotozoal compounds from Asparagus africanus. J Nat Prod 60:1017–1022
Perez-Victoria JM, Chiquero MJ, Conseil G, Dayan G, Di Pietro A, Barron D, Castanys S, Gamarro F (1999) Correlation between the affinity of flavonoids binding to the cytosolic site of Leishmania tropica multidrug transporter and their efficiency to revert parasite resistance to daunomycin. Biochemistry 38:1736–1743
Phillipson JD (1991) Assays for antimalarial and amoebicidal activities. In: Dey DM, Harborne JB (eds) Methods in plant biochemistry, vol 6, Assays in bioactivity. Academic Press, London, pp 135–152
Phillipson JD, Wright CW (1991) Can ethnopharmacology contribute to the development of antimalarial agents? J Ethnopharmacol 32:155–165
Phillipson J, Wright CW, Kirby GC, Warhust DC (1993) Tropical plants as sources of antiprotozoal agents. In: Downum KR, Romeo JR, Stafford HA (eds) Phytochemical potential of tropical plants, vol 27. Recent advances in phytochemistry. Plenum Press, New York, pp 1–40
Pinto CN, Dantas AP, De Moura KC, Emery FS, Polequevitch PF, Pinto MC, de Castro SL, Pinto AV (2000) Chemical reactivity studies with naphthoquinones from Tabebuia with anti-trypanosomal efficacy. Arzneimittelforschung 50:1120–1128
Posner GH (1998) Antimalarial peroxides in the qinghaosu (artemisinin) and yingzhaosu families. Expert Opin Ther Targets 8:1487–1493
Posner GH, Cumming JN, Woo S-H, Ploypradith P, Xie S, Shapiro TA (1998) Orally active antimalarial 3-substituted trioxanes: new synthetic methology and biological evaluation. J Med Chem 41:940–951
Rayo Camacho Corona M, Croft SL, Phillipson JD (2000) Natural products as sources of antiprotozoal drugs. Curr Opin Anti-Infect Investig Drugs 2:47–62
Ribeiro A, Pilo-Veloso D, Romanha AJ, Zani CL (1997) Trypanocidal flavonoids from Trixis vauthieri. J Nat Prod 60:836–841
Sairafianpour M, Christensen J, Staerk D, Budnik BA, Kharazmi A, Bagherzadeh K, Jaroszewski JW (2001) Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskia abrotanoides: new source of tanshinones. J Nat Prod. 64:1398–1403
Tandon JS, Srivastava V, Guru PY (1991) Iridoids: a new class of leishmanicidal agents from Nyctanthes arbortristis. J Nat Prod 54:1102–1104
Teixeira MJ, de Almeida YM, Viana JR, Holanda Filha JG, Rodrigues TP, Prata JRJr, Coelho IC, Rao VS, Pompeu MM (2001) In vitro and in vivo leishmanicidal activity of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol). Phytother Res 15:44–48
Thompson (1998) Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab 12:691–1705
Vennerstrom JL, Lovelace JK, Waits VB, Hanson WL, Klayman DL (1990) Berberine derivatives as antileishmanial drugs. Antimicrob Agents Chemother, 34:918–921
Weiss CR, Moideen SV, Croft SL, Houghton PJ (2000) Activity of extracts and isolated naphthoquinones from Kigelia pinnata against Plasmodium falciparum. J Nat Prod 63:1306–1309
Wright CW, Allen D, Cai Y, Chen Z, Phillipson JD (1994) Selective antiprotozoal activity of some Strychnos alkaloids. Phytother Res 8:149–152
Zhai L, Blom J, Chen M, Christensen BS, Kharazami A (1995) The antileishmanial agent licochalcone A interferes with the function of parasite mitochondria. Antimicrob Agents Chemother 39:2742–2748
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kayser, O., Kiderlen, A.F. & Croft, S.L. Natural products as antiparasitic drugs. Parasitol Res 90 (Suppl 2), S55–S62 (2003). https://doi.org/10.1007/s00436-002-0768-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-002-0768-3