The capability of minor quaternary benzophenanthridine alkaloids to inhibit TNF-α secretion and cyclooxygenase activity.

Quaternary benzophenanthridine alkaloids are known to have a wide range of biological effects, including antimicrobial, antifungal, anti-inflammatory, and antitumour activities. However, only sanguinarine and chelerythrine have been studied intensively. The aim of this study was to evaluate the anti-inflammatory potential of the five minor quaternary benzophenanthridine alkaloids sanguilutine, sanguirubine, chelirubine, chelilutine, and macarpine in vitro and to compare them with more thoroughly studied sanguinarine and chelerythrine. Before making cellbased assays, the cytotoxicity of the alkaloids was evaluated. The anti-inflammatory potential of the chosen alkaloids was evaluated as for their ability to modulate the lipopolysaccharideinduced secretion of tumour necrosis factor α (TNF-α) in the macrophage-like cell line THP-1. The cyclooxygenase (COX)-1 and COX-2 inhibitory activities were also measured. The results indicate that the presence of a methylenedioxy ring attached at carbon (C)7-C8 is important for reducing the secretion of TNF-α. Interestingly, this effect did not show a simple dependence on concentration. The selected alkaloids showed little or no anti-COX activity. The results obtained from the present experiments may provide additional information useful in understanding the structure-to-activity relationship of the quaternary benzophenanthridine alkaloids. The antiinflammatory potential and the cytotoxic effect are driven by the presence of a methylenedioxy ring attached at C7-C8 and C2-C3, respectively. [ABSTRACT FROM AUTHOR]