Alberton Elga Heloísa, Damazio Rosangela Guollo, Cazarolli Luisa Helena, Chiaradia Louise Domeneghini, Leal Paulo César, Nunes Ricardo José, Yunes Rosendo Augusto, Silva Fátima Regina Mena Barreto
Universidade Federal de Santa Catarina, Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Bairro Trindade, Florianópolis, SC, Brazil.
Chem Biol Interact. 2008 Feb 15;171(3):355-62. doi: 10.1016/j.cbi.2007.11.001. Epub 2007 Nov 17.
A series of chalcone derivatives from 3,4-methylenedioxybenzaldehyde and substituted acetophenones have been synthesized and investigated as antihyperglycemic agents in a glucose loaded animal model. Chalcones with biological activity were compared with lispro, regular insulin and tolbutamide effects on serum glucose levels. Compound 01, without substituent in the A-ring was not able to change glycemic levels. On the other hand, compounds 03, 04, 05, 09 and 10 with substitutions at position 3' and/or 4' in the A-ring caused significant reduction in serum glucose levels. Concerning the antihyperglycemic effect, compounds 03 and 05 (methoxy substituent) inhibited the hyperglycemia induced by glucose around 96% similar to that demonstrated for lispro insulin and tolbutamide at 60 min. A rapid and lasting antihyperglycemic effect was found with compound 09 and 10 (nitro substituent). In conclusion, besides the nature of the functional groups electron-donor substituent, as methoxy and hydroxyl or electron-acceptor, as nitro groups, the position of the group may be mandatory for biological activity.
已经合成了一系列由3,4-亚甲二氧基苯甲醛和取代苯乙酮衍生的查尔酮，并在葡萄糖负荷动物模型中作为抗高血糖药物进行了研究。将具有生物活性的查尔酮与赖脯胰岛素、常规胰岛素和甲苯磺丁脲对血糖水平的影响进行了比较。A环无取代基的化合物01不能改变血糖水平。另一方面，A环3'和/或4'位有取代基的化合物03、04、05、09和10可使血清葡萄糖水平显著降低。关于抗高血糖作用，化合物03和05（甲氧基取代基）在60分钟时抑制葡萄糖诱导的高血糖约96%，与赖脯胰岛素和甲苯磺丁脲相似。化合物09和10（硝基取代基）具有快速持久的抗高血糖作用。总之，除了官能团的性质（供电子取代基如甲氧基和羟基或吸电子取代基如硝基）外，基团的位置对于生物活性可能也是必不可少的。
