Binding of bisbenzylisoquinoline alkaloids to phosphatidylcholine vesicles and alveolar macrophages: relationship between binding affinity and antifibrogenic potential of these drugs.

Abstract

A group of bisbenzylisoquinoline alkaloids has been shown to exhibit various degrees of effectiveness in preventing silica-induced fibrosis in animal models. The objective of the present study was to characterize the binding of several of these alkaloids to phosphatidylcholine vesicles and rat alveolar macrophages using fluorometric and equilibrium dialysis methods, respectively. The lipid binding affinity of these alkaloids was found to depend upon several structural factors including hydrophobic substitutions, chiral configurations, and double oxygen bridge-restricted confirmation of the benzylisoquinoline moieties. Tetrandrine, which is a highly effective agent in preventing fibrosis, showed strong binding to both lipid vesicles and alveolar macrophages. In contrast, certain analogues of tetrandrine such as curine and tubocurine, which have little or no effect on silicosis, exhibited only weak binding to lipid vesicles and almost no binding to cells. The moderate binding affinity of fangchinoline to vesicles and cells corresponded to a moderate effectiveness of the compound as an antifibrogenic agent. Methoxyadiantifoline, an alkaloid of unknown antifibrogenic potential, also exhibited high binding affinities for lipid and cells. In conclusion, the results of these studies indicate that alveolar macrophages exhibit large binding capacities for certain members of this class of bisbenzylisoquinoline alkaloids. A positive correlation was observed between binding affinity to alveolar macrophages and the reported antifibrotic potency of these compounds. These data also suggest that the ability of these drugs to interact with alveolar macrophages may be a key step in inhibition of the progression of silica-induced pulmonary disease.

• Authors: J K Ma, C G Mo, C J Malanga, J Y Ma, V Castranova
• Journal: Experimental lung research (Exp Lung Res) 1991 Nov-Dec Vol. 17 Issue 6 Pg. 1061-77 ISSN: 0190-2148 [Print] England
• PMID: 1663032 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Alkaloids
• Anilino Naphthalenesulfonates
• Isoquinolines
• Phosphatidylcholines
• 1,2-Dipalmitoylphosphatidylcholine
• 1-anilino-8-naphthalenesulfonate
• Silicon Dioxide

Topics

• 1,2-Dipalmitoylphosphatidylcholine (metabolism)
• Alkaloids (chemistry, metabolism, pharmacology)
• Anilino Naphthalenesulfonates (metabolism)
• Animals
• Binding, Competitive
• Isoquinolines (chemistry, metabolism, pharmacology)
• Macrophages, Alveolar (metabolism)
• Phosphatidylcholines (metabolism)
• Pulmonary Fibrosis (chemically induced, prevention & control)
• Silicon Dioxide