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Antilipolytic effects of 1,8‐naphthyridine derivatives β‐adrenoceptor antagonists in rat white adipocytes
Author(s) -
Aljamal Jalal A.,
Badawneh Muwaffag
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12933
Subject(s) - isoprenaline , lipolysis , chemistry , antagonist , alprenolol , substituent , agonist , stereochemistry , endocrinology , adipose tissue , receptor , biochemistry , biology , stimulation
The rat fat cell β‐adrenoceptors were investigated by studying the effects of new 1,8‐naphthyridine derivatives synthesized starting from 7‐amino‐2‐chloro‐3‐phenyl‐1,8‐naphthyridine on lipolysis induced by isoprenaline, and alprenolol. Lipolysis induced by isoprenaline agonist was competitively antagonized by the 1,8‐naphthyridine analogue with a 7‐hydroxy‐2‐(4′‐methoxybenzylamine)‐6‐nitro‐3‐phenyl substituent designated as 3 . In contrast, 10, 50, and 100 μ m of 7‐methoxy and 7‐ethoxy derivatives did not modify the concentration–response curve of isoprenaline. A rightward shift of the curve was, however, observed with 50 μ m of a 7‐methoxy‐2‐(4′‐methoxybenzylamine)‐6‐amino‐3‐phenyl substituent designated as 10 . The selective β 1 ‐ AR antagonist, 7‐hydroxy‐4‐morpholinomethyl‐2‐piperazino‐1,8‐naphthyridine slightly reduced isoprenaline‐induced lipolysis only at high doses. Alprenolol‐mediated lipolytic effect was antagonized by derivative 3 , 10 and the selective β 3 ‐ AR antagonist SR 59,230A, but resistant to the selective β 1 ‐ AR antagonist 7‐hydroxy‐4‐morpholinomethyl‐2‐piperazino‐1,8‐naphthyridine. The results provide preliminary pharmacological evidence for the antilipolytic effect of the newly synthesized 1,8‐naphthyridine derivatives on rat fat cells. The analogues designated as 3 and 10 were the most potent antagonists of this series.