ABSTRACT
Abstract Four bisabolanes 1–4, including perezone (1) and triacetyl perezone (2), were isolated through a bioassay-guided fractionation of the extract obtained from the Caribbean gorgonian coral Pseudopterogorgia rigida collected during an expedition cruise to the Bahamas. All isolated compounds showed to be cytotoxic toward panel of four human tumor cell lines, as quantified by the MTT assay after 72 h incubation. Perezone (1), the most active one, was further analyzed, showing to be cytotoxic, but not selective, in a 12-cell line panel comprising tumor and non-tumor, as well as human and murine cells. Additionally, 1 was assayed for cytotoxicity against HL-60 leukemic cells. Pre-treatment with an acute free radical scavenger (L-NAC) before exposure of cells to perezone virtually eliminated the generation of intracellular ROS and lessened its severe cytotoxicity. The protective effect delivered by L-NAC evidences that the mechanism of perezone-induced cytotoxicity is partially associated to production of ROS and a consequent induction of oxidative stress.
ABSTRACT
This study evaluated the cholinesterase inhibitory activity of an alkaloid-rich fraction of stembark from Geissospermum vellosii (PP), and its effect on memory tests in mice. PP inhibited rat brain and electric eel acetylcholinesterase, as well as horse serum butyrylcholinesterase in a concentration-dependent manner with mean IC(50) values of 39.3 microg/mL, 2.9 microg/mL, and 1.6 microg/mL, respectively. The main alkaloid with anticholinesterase activity in PP was isolated and identified as geissospermine. PP significantly reduced scopolamine-induced amnesia in the passive avoidance and Morris water maze tests, at 30 mg/kg i.p. (given 45 min before the test sessions). At the highest effective dose (60 mg/kg), administration of PP did not result in noticeable peripheral or central cholinergic side effects. Only after administration of 200 mg/kg, mice showed convulsions affecting the whole body followed by death. These results show that compounds present in G. vellosii stembark have anticholinesterase activity, and that they can revert cognitive deficits in a model of cholinergic hypofunction.
Subject(s)
Acetylcholinesterase/drug effects , Apocynaceae/chemistry , Cholinesterase Inhibitors/pharmacology , Memory Disorders/drug therapy , Plant Extracts/therapeutic use , Plant Stems/chemistry , Scopolamine/toxicity , Animals , Avoidance Learning , Male , Maze Learning , Memory Disorders/chemically induced , Mice , Plant Extracts/pharmacologyABSTRACT
Ten indole alkaloids from the chloroform extract of stalk of Tabernaemontana australis (Muell. Arg) Miers were tentatively identified by GC-MS, viz., coronaridine (1), voacangine (2), voacangine hydroxyindolenine (3), rupicoline (4), ibogamine (5), ibogaine (6), ibogaline (7), desethyl-voacangine (8), voachalotine (9), and affinisine (10). Of these, the first four were isolated by silica gel open column chromatography, identified by uni- and bidimensional NMR, IR, MS and showed anti-cholinesterasic activity at the same concentration as the reference compounds physostigmine and galanthamine (detection limit of 0.01mM) by TLC assay using the modified Ellman's method.
