A study of the chemical constituents of the stem bark of Vitellaria paradoxa (Sapotaceae) has resulted in the isolation and characterization of a new ursane-type triterpenoid, 2β,3β,19α-trihydroxyurs-12-en-28-oic acid (1), together with seven known compounds: betulinic acid (2), 1α,2β,3β,19α-tretrahydroxyurs-12-en-28-oic acid (3), β-sitosterol (7), sigmasterol (8), (-)-epicatechin (9), (+)-catechin (10) and quercetin (11). The structure of the novel, ursane-type acid 1 was elucidated on the basis of detailed spectroscopic analysis including IR, HRMS (ESI), 1D and 2D NMR and a comparison to previously described, related natural products. Preliminary cytotoxicity assays against the MDA-MB-231 breast cancer cell line indicated that betulinic acid 2 and its corresponding methyl ester 5 were the most active compounds tested with IC50 values of 19.9 μM (17.2–23.1 μM, 95% CI) and 32.9 μM (24.9–43.4 μM, 95% CI), respectively. Esterification of acids 1–3 afforded the corresponding methyl esters 4–6 for additional structure-activity relationship (SAR) analysis. In general, the activity against the MDA-MB-231 breast cancer cell line increased upon esterification of the triterpenoids screened.
plant-derived natural productsursane family isolation structure elucidation Apoptosis/necrosis assay
This is a preview of subscription content, log in to check access
The authors would like to acknowledge the council for International Exchange of Scholars (CIES) for the J. William Fulbright Visiting Scholar program to Dr Kenneth Eyong. The Baylor CPRIT Synthesis and Drug Lead Discovery Laboratory (supported by the Cancer Prevention and Research Institute of Texas R1309 and Baylor University, College of Arts and Sciences) and the Molecular Bioscience Center hosted Dr. Eyong. The Departments of Chemistry & Biochemistry and Department of Biology at Baylor University are acknowledged for infrastructure and financial support. The University of Yaounde I and the Government of Cameroon are acknowledged for financial support through the Fonds d’Appuis a la Recherche.
Alavijeh MS, Chishty M, Qaiser Z, Alan M, Palmer AM (2005) Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. NeuroRx 2:554–571CrossRefPubMedPubMedCentralGoogle Scholar
Chave KJ, Garimella SV, Lipkowitz S (2010) Triple negative breast cancer cell lines: One tool in the search for better treatment of triple negative breast cancer. Breast Dis 32(1–2):35–48CrossRefGoogle Scholar
Eyong KO, Foyet HS, Baïrys G, Gabriel GN, Asongalem EA, Lagojda A, Lamshöft M (2015) A new ursane triterpenoic acid and other potential anti-inflammatory and anti-arthritic constituents from EtOAc extracts of Vitellaria paradoxa stem bark. Ethnopharmacology 174:277–286CrossRefPubMedGoogle Scholar
Foyet HS, Tsala DE, Bodo JCZE, Azanfack NC, Toussoumna LH, Eyong KO (2015) Anti-inflammatory and anti-arthritic activity of a methanol extract from Vitellaria paradoxa stem bark. Pharmacognosy Res 7:367–377CrossRefPubMedCentralGoogle Scholar
Gennari C, Castoldi D, Sharon O (2007) Natural products with taxol-like anti-tumor activity: synthetic approaches to eleutherobin and dictyostatin. Pure Appl Chem 79:173–180CrossRefGoogle Scholar
Harvey AL, Edrada-Ebel RA, Quinn RJ (2015) The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 14:111–129CrossRefPubMedGoogle Scholar
Jiofack T, Fokunang C, Guedje N, Kemeuze V, Fongnzossie E, Nkongmeneck BA, Mapongmetsem PM, Tsabang N (2010) Ethnobotanical uses of medicinal plants of two ethnoecological regions of Cameroon. Int J Med Med Sci 2:60–79Google Scholar
Lacroix M, Leclercq G (2004) Relevance of breast cancer cell lines as models for breast tumors: an update. Breast Cancer Res Treat 83(3):249–89CrossRefPubMedGoogle Scholar
Liu WJ, Hou XQ, Chen H, Liang JY, Sun JJ (2016) Chemical constituents from Agrimonia pilosa Ledeb. and their chemotaxonomic significance. Nat Prod Res 30(21):2495–2499CrossRefPubMedGoogle Scholar
Zhang J, Kurita M, Shinozaki T, Ukiya M, Yasukawa K, Shimizu N, Tokuda H, Masters ET, Akihisa M, Akihisa T (2014) Triterpene glycosides and other polar constituents of shea (Vitellaria paradoxa) kernels and their bioactivities. Phytochemistry 108:157–170CrossRefPubMedGoogle Scholar