Phenethyisoquinoline alkaloids from the leaves of Androcymbium palaestinum

Abstract

Thirteen compounds were isolated from the methanolic extract of the leaves of Androcymbium palaestinum Baker (Colchicaceae). Of these, three were new, two were new natural products, and eight were known. The new isolated compounds were (+)-1-demethylandrocine (5), (−)andropalaestine (8), and (+)-2-demethyl-β-lumicolchicone (10), while the new natural products were (+)-O-methylkreysigine-N-oxide (3) and (+)-O,O-dimethylautumnaline (9). Moreover, two known compounds are reported for the first time from this species, specifically (−)-colchicine ( 11) and (−)-3-demethyldemecolcine (13). The structures of the isolated compounds were elucidated using a series of spectroscopic and spectrometric techniques, principally HRESIMS, 1D-NMR ( 1 H and 13 C-NMR) and 2D-NMR (COSY, edited-HSQC, and HMBC). ECD spectroscopy was used for assigning the absolute configurations of compounds 3, 5, and 10. The cytotoxic activities of the isolated compounds were evaluated using the MDA-MB-435 (melanoma), MDA-MB-231 (breast), and OVCAR3 (ovary) cancer cell lines. Compound 11 was the most potent against all tested cell lines, with IC 50 values of 12, 95 and 23 nM, respectively.

Discovery and development of botanical natural products and their analogues as therapeutics for ovarian cancer

“…When tested for potency in OVCAR3 cells, they found the amino methylated naturally occurring analogue (IC 50 = 77 nM) of colchicine to be 3 fold less potent than colchicine (IC 50 = 23 nM) but 10 fold more potent than the de-methoxy naturally occurring analogue (IC 50 = 2230 nM). 98 Another SAR study tested in ovarian cancer cells SKOV3 found 7-deacetyl-10-alkyl thiochochicine derivatives displayed significantly better potency than the natural product. The C10 thiomethane derivative displayed the most potent activity in SKOV3 cells with an IC 50 of 1.3 nM.…”

“…97 One recent colchicine SAR campaign that tests their analogues an in ovarian cancer cell lines is from El-Elimat and co-workers. 98 El-Elimat and coworkers isolated (−)-colchicine in a new species, Androcymbium palaestinum. When tested for potency in OVCAR3 cells, they found the amino methylated naturally occurring analogue (IC 50 = 77 nM) of colchicine to be 3 fold less potent than colchicine (IC 50 = 23 nM) but 10 fold more potent than the de-methoxy naturally occurring analogue (IC 50 = 2230 nM).…”

Coumarins, dihydroisocoumarins, a dibenzo-α-pyrone, a meroterpenoid, and a merodrimane from Talaromyces amestolkiae

“…As part of an ongoing project to uncover new chemistry from nature [1], [2], [3], [4], [5], our group has been investigating freshwater fungi [6], [7], [8], [9], [10], [11]. Lignicolous freshwater fungi represent a viable resource for discovering new secondary metabolites with a broad range of biological activities [12], [13], [14].…”