Cogniauxia Podolaena: Bioassay-Guided Fractionation of Defoliated Stems, Isolation of Active Compounds, Antiplasmodial Activity and Cytotoxicity

Abstract

Cogniauxia podolaena Baill. (Cucurbitaceae) is traditionally used in Congo Brazzaville for the treatment of malaria. We assessed the antiplasmodial activity of the plant and isolated some of the compounds responsible for this activity. It was the first time that a chemical study of this plant has been undertaken. Three triterpenes were isolated: cucurbitacin B (1), cucurbitacin D (2) and 20-epibryonolic acid (3) and their structures were assigned from spectroscopic evidence and comparison with published data. The crystallographic structure of 3 was determined. All fractions and compounds obtained in this study were assayed for antiplasmodial activity (on FcM29, a chloroquine-resistant strain of P. falciparum) and cytotoxicity (on KB and Vero cell lines). The IC₅₀ values of 1, 2 and 3 are 1.6, 4 and 2 μg/mL on FcM29. Both 1 and 2 have a high cytotoxicity whereas 3 shows a better selectivity index.

Cogniauxia podolaena - Cucurbitaceae - Cucurbitacins - 20-epibryonolic acid - antiplasmodial activity - cytotoxicity

References

• 1 Mbatchi S F, Mbatchi B, Banzouzi J T, Bansimba T, Nsonde Ntandou G F, Ouamba J M. et al . In vitro antiplasmodial activity of 18 plants used in Congo Brazzaville traditional medicine.  J Ethnopharmacol. 2006;  104 168-74.
• 2 Che C T, Fang X, Phoebe C H, Kinghorn D, Farnsworth N R, Yellin B. et al . High-field ¹H-NMR spectral analysis of some cucurbitacins.  J Nat Prod. 1985;  48 429-34
• 3 Jacobs H, Singh T, Reynolds W, McLean S. Isolation and ¹³C-NMR assignments of cucurbitacins from Cayaponia angustiloba, Cayaponia racemosa, and Gurania subumbellata. .  J Nat Prod. 1990;  53 1600-5
• 4 Chang Y S, Lin M S, Jiang R L, Huang S C, Ho L K. 20-Epibryonolic acid, phytosterols and ellagic acid from Coriaria intermedia. .  Phytochemistry. 1996;  42 559-60
• 5 Diatewa M, Badila Samba C, Coffi Hondi Assah T, Abena A A. Hypoglycemic and antihyperglycemic effects of diethyl ether fraction isolated from the aqueous extract of the leaves of Cogniauxia podoleana Baillon in normal and alloxan-induced diabetic rats.  J Ethnopharmacol. 2004;  92 229-32
• 6 Hallwirth H J. Cucurbitacin compositions for the treatment of malaria. SG Patent 122 745 2006
• 7 Young A J, Halaweish F T. Cucurbitacin derivatives: development of potential anticancer candidates via computational chemistry. 42nd Midwest Regional Meeting of the American Chemical Society Kansas City, MO; 2007
• 8 Otwinovski Z, Minor W. Macromolecular crystallography, Part A.  Methods Enzymol. 1997;  276 307-26
• 9 Nonius B V. ”Collect” data collection software. 1999.
• 10 Sheldrick G M. Shelx97: Program for the refinement of crystal structures from diffraction data. Göttingen; University of Göttingen 1997.
• 11 Trager W, Jensen B. Human malaria parasites in continuous culture.  Science. 1976;  193 673-5.
• 12 Benoit-Vical F, Valentin A, Mallie M, Bastide J M, Bessiere J M. In vitro antimalarial activity and cytotoxicity of Cochlospermum tinctorium and C. planchonii leaf extracts and essential oils.  Planta Med. 1999;  65 378-81

1 First co-authors (JTB and PNS) have contributed equally to this manuscript