Lupane-3,16-dione

Guggulsterone [4, 17(20)-pregnadiene-3, 16-dione] is a plant sterol derived from the gum resin of the tree Commiphora wightii. The gum resin of the guggul tree has been used in traditional medicine for centuries to treat obesity, liver disorders, internal tumors, malignant sores, ulcers, urinary complaints, intestinal worms, leucoderma, sinus, edema and sudden paralytic seizures. Guggulsterone has been shown to modulate the nuclear receptors, farnesoid X receptor, pregnane X receptor, CYP 2b10 gene expression, and the bile salt export pump for cholesterol elimination. Recent research indicates that the active components of gum guggul, E- and Zguggulsterone have the potential to both prevent and treat cancers. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP, and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases, inhibition of Akt, and activation of JNK. Guggulsterone modulates the expression of gene products involved in metastasis (MMP-9, COX-2, and VEGF) of tumor cells. Guggulsterone mediates gene expression through the modulation of several transcription factors, including NF-κB, STAT3, C/EBPα, androgen receptor, and glucocorticoid receptors. This review describes the anti-cancer properties, molecular targets, and the apoptotic effects of guggulsterone.

Androsta-1,4-dien-3,16-dione was isolated for the first time from the plant kingdom of the ethanolic extract of the Ravenala madagascariensis' inflorescence by the bio-guided method. Its structure was elucidated by NMR and MS spectroscopic data analysis. The vascular effects of ethanol extracts, fractions and androsta-1,4-dien-3,16-dione were assessed on the phenylephrine pre-contracted isolated rat aorta. The isolated compound exerted the most potent vaso-relaxing effect (EC50 = 109.32 ± 15.82 µM) than the ethanol extract and fractions. The pharmacological mechanism of its vaso-relaxing action was analysed on isolated rat aorta using free-endothelial vascular tissue, specific contracting reagents (CaCl2 and KCl), antagonist (propranolol), enzyme inhibitors (L-NAME, methylene blue) and channel blocker (glibenclamide). Its vaso-relaxing activity could be due, at least partly, to the non-specific inhibition of the calcic influx.

Friedelan-3-one (1) and friedelane-3,16-dione (2) isolated from leaves and branches of Maytenus robusta Reissek were subjected to structural modifications via nucleophilic addition to the carbonyl group and Baeyer-Villiger oxidation in order to synthesize potential cytotoxic compounds. The oximes friedelane-3-hydroxyimino (3) and 3-hydroxyiminofriedelan-16-one (4) together with the lactones friedelane-3,4-lactone (5) and 3,4-lactonefriedelan-16-one (6) were characterized by IR and NMR spectroscopic analyses. Compounds 4 and 6 are reported for the first time. Cytotoxic screening via MTT assay in human leukemia cell lines (THP-1 and K562) demonstrated no significant improvement of compounds 3-6 when compared to the starting materials. Only compounds 3 and 5 demonstrated an improvement against K562 cells. However, the same assay on ovarian and breast cancer cell lines (TOV-21G and MDA-MB-231) showed a reduction in the IC50 for compounds 4-6, indicating that ring A modifications may enhance the biological potential.