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Binding of bisbenzylisoquinoline alkaloids to phosphatidylcholine vesicles and alveolar macrophages: relationship between binding affinity and antifibrogenic potential of these drugs.
Ma-JK; Mo-C; Malanga-CJ; Ma-JY; Castranova-V
Exp Lung Res 1991 Nov; 17(6):1061-1077
The binding of bisbenzylisoquinoline (BBIQ) alkaloids to phosphatidylcholine vesicles and alveolar macrophages was studied in- vitro. The purpose of the study was to determine if the antifibrotic effectiveness of the compounds could be related to their ability to bind to biological membranes. Tetrandrine (TE), fangchinoline (FA), berbamine, cepharanthine (CE), tubocurine, curine, cycleanine, or methoxyadiantifoline (ME) were incubated with dipalmitoylphosphatidylcholine (DPPC) vesicles. The binding affinity of the compounds was determined fluorometrically using 1- anilino-8-naphthalene-sulfonate as a fluorescence probe. The lipid binding affinities of the alkaloids were measured using a fluorometric titration technique. Their lipid binding affinity ranked in decreasing order was ME, TE, CE, cycleanine, FA, berbamine, and tubocurine approximately equal to curine. The overall binding affinity of the compounds for DPPC was similar, ME being the most potent, followed by TE, CE, cycleanine, FA, berbamine, tubocurine, and curine. ME, TE, FA, curine, or tubocurine were incubated with alveolar macrophages isolated from male Sprague- Dawley-rats. The extent of binding to the macrophages was determined by an equilibrium dialysis technique. The overall binding affinity of the compounds ranked in descending order was TE, ME, FA, and tubocurine approximately equal to curine. The authors conclude that BBIQ alkaloids exhibit structure dependent binding to DPPC vesicles and alveolar macrophages in-vitro. The structural features that promote higher bonding affinity include the presence of a methoxy group, a chiral configuration, and the presence of a double oxygen bridge within the molecule. The degree of binding to DPPC vesicles and alveolar macrophages is strongly, positively correlated with the lipophilicity and antifibrotic effectiveness of the compounds. BBIQ alkaloids may be useful probes for examining the etiology of pulmonary fibrosis.
NIOSH-Author; In-vitro-studies; Molecular-structure; Chemical-binding; Phospholipids; Alveolar-cells; Lung-fibrosis; Laboratory-animals; Quinolines
Issue of Publication
Experimental Lung Research
Page last reviewed: April 12, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division