Instituto de Genetica e Bioquimica, INGEB, Universidade Federal de Uberlandia, UFU, Uberlandia-MG, Brazil.
Curr Top Med Chem. 2011;11(20):2566-77. doi: 10.2174/156802611797633438.
Four compounds (isoquercitrin, myricetin-3-O-glucoside, catechin and gallocatechin) were isolated from lyophilized aqueous extract of Schizolobium parahyba leaves by chromatography on Sephadex LH-20, followed by semipreparative HPLC using a C-18 column, and identified by 1H and 13C NMR. The compounds were then, tested against hemorrhagic and fibrinogenolytic activities of Bothrops crude venoms and isolated metalloproteinases. The inhibitors neutralized the biological and enzymatic activities of Bothrops venoms and toxins isolated from B. jararacussu and B. neuwiedi venoms. The results showed that gallocatechin and myricetin-3-O-glucoside are good inhibitors of hemorrhagic and fibrinogenolytic activities of metalloproteinases, respectively. Gallocatechin also inhibited the myotoxic activity of both B. alternatus venom and BnSP-6 (Lys49 PhospholipaseA2 from B. neuwiedi). Circular dichroism and docking simulation studies were performed in order to investigate the possible interaction between BnSP-6 and gallocatechin. This is the first time these compounds and their anti-ophidian properties are reported for S. parahyba species. Forthcoming studies involving X-ray co-crystallization, will be of great importance for the development of new therapeutic agents for the treatment of ophidian accidents and for the better understanding of the structure/function relationship of venom toxins.
四种化合物（异槲皮苷、杨梅素-3-O-葡萄糖苷、儿茶素和没食子儿茶素）通过 Sephadex LH-20 色谱法从冻干的 Schizolobium parahyba 叶的水提物中分离出来，然后使用 C-18 柱通过半制备 HPLC 进行分离，并通过 1H 和 13C NMR 进行鉴定。然后，将这些化合物针对 Bothrops 粗毒液和分离的金属蛋白酶的出血和纤维蛋白溶活性进行了测试。抑制剂中和了 Bothrops 毒液和从 B. jararacussu 和 B. neuwiedi 毒液中分离出的毒素的生物学和酶活性。结果表明，没食子儿茶素和杨梅素-3-O-葡萄糖苷分别是金属蛋白酶出血和纤维蛋白溶活性的良好抑制剂。没食子儿茶素还抑制了 B. alternatus 毒液和 BnSP-6（来自 B. neuwiedi 的 Lys49 磷脂酶 A2）的肌毒性活性。进行了圆二色谱和对接模拟研究，以研究 BnSP-6 和没食子儿茶素之间可能的相互作用。这是首次报道这些化合物及其对 S. parahyba 物种的抗蛇毒特性。即将进行的涉及 X 射线共结晶的研究对于开发治疗蛇咬伤的新治疗剂以及更好地理解毒液毒素的结构/功能关系将非常重要。
