Antilipolytic effects of 1,8‐naphthyridine derivatives β‐adrenoceptor antagonists in rat white adipocytes

Abstract

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 μm 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 μm of a 7-methoxy-2-(4'-methoxybenzylamine)-6-amino-3-phenyl substituent designated as 10. The selective β -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 -AR antagonist SR 59,230A, but resistant to the selective β -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.

Recent Developments and Multiple Biological Activities Available With 1, 8-Naphthyridine Derivatives: A Review

“…Aljamal and Badawneh [130] investigate the antilipolytic activity of the new NPTR derivatives (108a and b) on lipolysis induced rat fat cell β-adrenoceptors by isoprenaline and alprenolol. The NPTR derivatives substituted with 7-hydroxy-2-(4'-methoxybenzylamine)-6-nitro-3-phenyl (108a) and 7-methoxy-N2-(4-methoxybenzyl)-3phenyl-1,8-naphthyridine-2,6-diamine (108b) show the maximum antilipolytic effect.…”