Potentiation of cADPR-induced Ca2+-release by methylxanthine analogues

Rosaria A. Cavallaro, Luigi Filocamo, Annamaria Galuppi, Antony Galione, Mario Brufani, Armando A. Genazzani

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Caffeine and other methylxanthines are known to induce Ca2+-release from intracellular stores via the ryanodine receptor. In the present work, a range of caffeine analogues, in which methyl groups at the 1 and 7 positions were replaced with alkyl chains containing different functional groups (oxo, hydroxyl, propargyl, ester, and acids), were synthesized. These compounds were then screened for their ability to potentiate Ca2+-release induced by cADPR (an endogenous modulator of ryanodine receptors) in sea urchin egg homogenates. Two of the synthesized methylxanthines, 1,3-dimethyl-7-(7- hydroxyoctyl)xanthine (37) and 3-methyl-7-(7-oxooctyl)-1-propargylxanthine (66), were shown to be more potent than caffeine in potentiating cADPR- induced Ca2+-release, while 1,3-dimethyl-7-(5-ethylcarboxypentyl)xanthine (14) was shown to be more efficacious. The development of new methylxanthine analogues may lead to a better understanding of ryanodine receptor function and could possibly provide novel therapeutic agents.

Lingua originaleInglese
pagine (da-a)2527-2534
Numero di pagine8
RivistaJournal of Medicinal Chemistry
Volume42
Numero di pubblicazione14
DOI
Stato di pubblicazionePubblicato - 15 lug 1999
Pubblicato esternamente

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