Cytotoxic alkaloids from the root of Zanthoxylum paracanthum (mildbr) Kokwaro.

Chemical investigation of the root of Zanthoxylum paracanthum afforded 1 new alkamide derivative, (2E,4E)-6-oxo-N-isobutyldeca-2,4-dienamide (1) together with 10 known congeners including one phenolic amide (2), four benzophenanthridines (3 - 6), three indolonaphthyridines (7 - 9) and two lignans (10 and 11). Their structures were elucidated by a combination of spectroscopic and spectrometric data. Using resazurin reduction assay, the crude extract (10 µg/mL) and isolates (10 µM) were screened for their cytotoxic activities against the drug-sensitive (CCRF-CEM) leukemia cell line and its multidrug-resistant counterpart (CEM/ADR5000). Compounds 3, 4 and 6 showed cytotoxicity against CCRF-CEM with IC50 values of 2.00 ± 0.33, 2.31 ± 0.20 and 0.11 ± 0.04 µM, respectively. Only compound 6 exhibited strong cytotoxic activity against CEM/ADR5000 with an IC50 value of 2.34 ± 0.34 µM in comparison with the standard drug doxorubicin which showed IC50 values of 0.01 ± 0.14 (CCRF-CEM) and 26.78 ± 3.30 µM (CEM/ADR5000).

In vitro anti-cancer efficacy and phyto-chemical screening of solvent extracts of Kigelia africana (Lam.) Benth.

BACKGROUND AND OBJECTIVES: Kigelia africana is a medicinal plant growing naturally in many parts of Africa. In Kenya, a water concoction of the plant is used to treat breast and prostate cancers. Laboratory data on its anti-cancer activity and active principles is limited, hence no scientific rationale for its medicinal use. This study reports on in-vitro toxic activities of dichloromethane and methanol extracts of the plant against human breast cancer cells and phytochemical screening of the two extracts. METHODOLOGY: Plant extracts were obtained by sequential solvent extraction of dry plant material (stem bark) using analytical grade dichloromethane: methanol (1:1) and methanol (Sigma Aldrich). In-vitro anti-cancer activities of the extracts were determined using the suphorhodamine (SRB) assay against a human breast cancer cell line (HCC 1937). Preliminary Thin layer chromatography of plant extracts was done using POLYGRAM® SIL G/UV254 plates (Merck) to establish presence of different classes of secondary metabolites. RESULTS: In-vitro cytotoxic activities of the two extracts were significantly different (P = 0.05). The methanol extract exhibited higher activity (IC50 = 26.02 µg/ml) compared to that of dichloromethane: methanol (1:1) (IC50 = 55.01 µg/ml). Phyto-chemical screening of the two extracts revealed the presence of terpenoids, phenols, steroids and flavonoids. CONCLUSION: The high in-vitro anti-cancer activities of solvent extracts of Kigelia africana justify its use in traditional medicine to manage breast cancer. Phytochemical analysis of the extracts reveal similar profiles hence the differences in their anti-cancer activities can be attributed to quantitative variations of various classes of secondary metabolites.

Anti-inflammatory norhopanes from the root bark of Fagaropsis angolensis (Engl.) H.M.Gardner.

Two new norhopane derivatives namely 3ß,6ß,22-trihydroxy-7ß,11α-di[(4-hydroxybenzoyl)oxy]-21αH-24-norhopa-4(23)-ene (1) and 3ß,6ß,22-trihydroxy-7ß-[(4-hydroxybenzoyl)oxy]-21αH-24-norhopa-4(23)-ene (2) together with two previously reported compounds, including a norhopane, 3ß,6ß,11α-trihydroxy-7ß-[(4-hydroxybenzoyl)oxy]-24-norhopa-4(23),17(21)-diene (3) and a norneohopane, (21αH)-24-norneohopa-4(23), 22(29)-diene-3ß,6ß,7ß-triol 7-caffeate (4) were isolated from the root bark of Fagaropsis angolensis. Elucidation of their structures was achieved by spectroscopic (NMR, IR and UV) and spectrometric (HRESIMS) data and by comparison of these data with those of related compounds in the literature. Compounds 1-4 were evaluated for their anti-inflammatory activity by measuring the levels of cytokines, IL-1ß, IL-2, GM-CSF and TNF-α in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC). All tested compounds decreased secretion of IL-1ß and TNF-α. Compounds 2 and 4 caused significant decrease of the production of IL-2, GM-CSF and TNF-α compared to the reference drug, ibuprofen. These findings showed that the root barks of F. angolensis are rich source of norhopane derivatives and further provide a scientific rationale of using this plant in Kenyan folk medicine to relieve pain.