Effect of the dibenzylbutyrolactone lignan (-)-hinokinin on doxorubicin and methyl methanesulfonate clastogenicity in V79 Chinese hamster lung fibroblasts. | LitMetric
Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista Júlio de Mesquita Filho, Rodovia Araraquara-Jaú Km 1, 14801-902 Araraquara, São Paulo, Brazil.
Published: July 2010
AI Article Synopsis
Article Abstract
The dibenzylbutyrolactone lignan (-)-hinokinin (HK) was obtained by partial synthesis from (-)-cubebin, isolated from the dry seeds of the pepper, Piper cubeba. In view of the trypanocidal activity of HK and its potential as a lead compound for drug development, evaluation of its possible genotoxic activity is required. We have tested HK for possible genotoxicity and evaluated the compound's effect on the activity of the clastogens doxorubicin (DXR) and methyl methanesulfonate (MMS) in the micronucleus (MN) assay with Chinese hamster lung fibroblast V79 cells. HK alone did not induce MN, at concentrations up to 128microM. In combined treatments, HK reduced the frequency of MN induced by MMS. With respect to DXR, HK exerted a protective effect at lower concentrations, but at higher concentrations it potentiated DXR clastogenicity.
Although Aristolochia plants remain controversial due to their toxicity, this group of perianth-bearing plants, which includes the medicinal species Aristolochia esperanzae, is among the most relevant from an ethnobotanical perspective. All parts of A. esperanzae are used in popular medicine in the form of infusion for the treatment of rheumatism.
Tetrahydrofuran ring formation from dibenzylbutyrolactone lignans is a key step in the biosynthesis of aryltetralin lignans including deoxypodophyllotoxin and podophyllotoxin. Previously, Fe(II)- and 2-oxoglutarate-dependent dioxygenase (2-ODD) from Podophyllum hexandrum (Himalayan mayapple, Berberidaceae) was found to catalyze the cyclization of a dibenzylbutyrolactone lignan, yatein, to give deoxypodophyllotoxin and designated as deoxypodophyllotoxin synthase (DPS). Recently, we reported that the biosynthesis of deoxypodophyllotoxin and podophyllotoxin evolved in a lineage-specific manner in phylogenetically unrelated plant species such as P.
A short and efficient catalytic asymmetric protection-free synthesis of dibenzylbutyrolactone lignans, such as (-)-hinokinin, (-)-yatein, (-)-bursehernin, (-)-pluviatolide, and their 7'-hydroxylignans - (7')-parabenzlactone, (7')-hydroxyyatein, (7')-hydroxybursehernin, and (7')-hydroxy pluviatolide, respectively, is described. The syntheses of (+)-isostegane and the formal synthesis of (-)-podophyllotoxin and bicubebins are also described. Organocatalytic aldol-reduction-lactonization and Pd/C-catalyzed hydrogenative debromination are two-pot sequential reactions for the enantioselective synthesis of hydroxybutyrolactone 13b with excellent diastereo- and enantioselectivity (dr 33 : 1 and >99% ee).
Dibenzylbutyrolactone lignans (DBLs) are a class of natural products with a wide variety of biological activities. Due to their potential for the development of human therapeutic agents, DBLs have been subjected to various SAR studies in order to optimise activity. Previous reports have mainly considered changes on the aromatic rings and at the benzylic carbons of the compounds, whilst the effects of substituents in the lactone, at the C-9' position, have been relatively unexplored.
Arctigenin is a bioactive dibenzylbutyrolactone-type lignan exhibiting various pharmacological activities. The neuroprotective effects of arctigenin were demonstrated to be mediated via inhibition of AMPA and KA type glutamate receptors in the somatosensory cortex of the rat brain. The aim of this study was to compare the effects of arctigenin with matairesinol and trachelogenin on synaptic activity in rat brain slices.
