- Potentiation of cADPR-induced Ca2+-release by methylxanthine analogues
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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.
- Cavallaro, Rosaria A.,Filocamo, Luigi,Galuppi, Annamaria,Galione, Antony,Brufani, Mario,Genazzani, Armando A.
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p. 2527 - 2534
(2007/10/03)
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- Stereoselective Synthesis of 14-Azaestra-17-Thia-1,3,5(10)-Triene
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Racemic 14-aza-8-isoestra-17-thia-1,3,5(10)-triene derivatives are obtained by stereoselective addition of thiirane and methylthiirane at the C=N bond of cis-1,2,4a,5,6,10b-hexahydro-8-methoxy-3-methylbenzo[f]quinoline. Configuration in crystal state of unsubstituted in position 16 compound with cis-fusion of C and D rings established by X-ray structural investigation. Attempt to obtain analogs of the compounds with naturally fused B and C rings failed.
- Sokolov,Salfetnikova,Potekhin
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p. 838 - 846
(2007/10/03)
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- Thermostable Enzymes in Organic Synthesis, Part 6. Total synthesis of (S)-(-)-Zearalenone using a TBADH-Generated Trifunctional Chiron
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Chiral alcohols produced by Thermoanaerobium brockii alcohol dehydrogenase (TBADH)-catalysed asymmetric reduction of polyfunctional ketones are useful building blocks for natural products synthesis.In particular, the ability of TBADH to discriminate between two ketones having equal chemical reactivity is demonstrated by enzymatic reduction of dec-9-ene-2,6-dione to produce optically pure (S)-2-hydroxydec-9-en-6-one.The total synthesis of (S)-(-)-zearalenone with optical purity that exceeds 99.5percent has been achieved by using the latter compound as a starting material.
- Keinan, Ehud,Sinha, Subhash C.,Sinha-Bagchi, Anjana
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p. 3333 - 3340
(2007/10/02)
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