Favier Laura S, María Alejandra O M, Wendel Graciela H, Borkowski Eduardo J, Giordano Oscar S, Pelzer Lilian, Tonn Carlos E
INTEQUI-CONICET-UNSL, Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina.
J Ethnopharmacol. 2005 Sep 14;100(3):260-7. doi: 10.1016/j.jep.2005.02.042.
The preventive effect of natural xanthanolides as well as a series of synthetic derivatives on ulcer formation induced by absolute ethanol in rats was examined. Among the compounds tested, xanthatin gave the strongest protective activity. The inhibitory action exerted by this molecule on the lesions induced by 0.6N HCl and 0.2N NaOH was highly significant, reducing ulceration in the range of 58-96% at a dose from 12.5 to 100mg/kg. These results appear to confirm that the presence of a non-hindered alpha,beta-unsaturated carbonyl group seems to be an essential structural requirement for the gastric cytoprotective activity of these compounds. In order to explore this possibility, a theoretical conformational analysis was performed. We suggest that the mechanism of protection would involve, at least in part, a nucleophylic attack of the sulfhydryl group from the biological molecules present in the gastric mucosa to electrophylic carbons accessible in suitable Michael acceptors.
研究了天然黄原内酯以及一系列合成衍生物对大鼠无水乙醇诱导的溃疡形成的预防作用。在所测试的化合物中，苍耳素具有最强的保护活性。该分子对0.6N盐酸和0.2N氢氧化钠诱导的损伤的抑制作用非常显著，在12.5至100mg/kg的剂量下，溃疡减少幅度在58-96%之间。这些结果似乎证实，存在未受阻的α,β-不饱和羰基似乎是这些化合物具有胃细胞保护活性的必要结构要求。为了探究这种可能性，进行了理论构象分析。我们认为，保护机制至少部分涉及胃黏膜中生物分子的巯基对合适的迈克尔受体中可及的亲电碳的亲核攻击。
