Studies of the binding of bisbenzylisoquinoline alkaloids to phosphatidylcholine vesicles and alveolar macrophages in relation to their antifibrogenic potential.
Ma-JK; Mo-C; Malanga-CJ; Ma-JY; Castranova-V
Respirable dust in the mineral industries, proceedings of the 3rd symposium on respirable dust in the mineral industries, October 17-19, 1990, Pittsburgh, Pennsylvania. Frantz RL, Ramani RV, eds. Littleton, CO: Society for Mining, Metallurgy, and Exploration, Inc., 1991 Jan; :153-158
The relative lipophilicity and binding to phosphatidylcholine vesicles and rat alveolar macrophages of bisbenzylisoquinoline (BBIQ) alkaloids were compared and discussed in terms of their structures and antifibrogenic activities in silica (14808607) induced fibrosis. The BBIQs tested included tetrandrine (TE), fangchinoline (FA), berbamine (BE), cepharanthine (CE), tubocurine (TU), curine, cycleanine (CY) and methoxyadiantifoline (ME). ME, with nine methoxy groups, had the highest lipophilicity, followed by TE, CY, CE, FA and BE, with CU and TU, both containing two hydroxy groups, the least lipophilic. Relative binding affinities to dipalmitoyl-phosphatidylcholine lipid vesicles, measured by fluorescence and analyzed using the Scatchard equation, was consistent with the order of lipophilicity. An equilibrium dialysis method was employed to determined the binding affinities of the BBIQ alkaloids to Sprague-Dawley-rat alveolar macrophages. In this assay, TE was shown to have the greatest binding affinity, followed by ME and FA. No binding activity was detected for CU or TU. A statistical correlation between relative macrophage binding ability and antifibrotic activity was calculated. The authors conclude that the interaction of TE, ME and FA with alveolar macrophages may inhibit silica induced lung fibrosis, preventing further progression of silica induced pulmonary disease.
Lung-cells; Alveolar-cells; Quinolines; Molecular-structure; Silicosis; Lung-fibrosis; Pulmonary-disorders; Respiratory-system-disorders; Medical-treatment; Mammalian-cells
Joseph K.H. Ma, School of Pharmacy, West Virginia University, Morgantown, WV
Respirable dust in the mineral industries, proceedings of the 3rd symposium on respirable dust in the mineral industries, October 17-19, 1990, Pittsburgh, Pennsylvania