Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues

Background: dihydrocorynantheol (dhc) is an alkaloid compound isolated from esenbeckia leiocarpa engl. that has demonstrated anti-inflammatory properties in experimental models. the aim of this study was to investigate whether the modification of the chemical structure of dhc could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan. methods: dhc was isolated from esenbeckia leiocarpa engl. capillary electrophoresis,physical characteristics,spectral data produced by infrared analysis and nuclearmagnetic resonance (1hand 13c),andmass spectrometry analysiswere used to identify and elucidate dhc structure. the dhc compound was subjected to chemical structural modifications by nucleophilic substitution reactions,yielding five analogous compounds: acetyl (1),p-methylbenzoyl (2),benzoyl (3),p-methoxybenzoyl (4) and p-chlorobenzoyl (5). swiss mice were used throughout the experiments. pro-inflammatory parameters leukocyte migration,exudate concentrations and myeloperoxidase (mpo) activity were quantified in the fluid leakage from the mouse pleural cavities at 4 h after pleurisy induction. results: dhc and its analogues acetyl,p-methylbenzoyl,benzoyl,p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration andmpoactivity (p > 0.05). onlydhcsignificantly decreased the exudate concentrations (p > 0.01). conclusions: dhc was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan.we did not determine what physicochemical modifications altered the anti-inflammatory effect of dhc,but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the dhc.copyright © 2013 by institute of pharmacology polish academy of sciences.