新型磺酰腙类化合物作为抗糖尿病药物的合成、溶解性、血浆稳定性及药理评价
Synthesis, solubility, plasma stability, and pharmacological evaluation of novel sulfonylhydrazones designed as anti-diabetic agents.
作者信息
Zapata-Sudo Gisele, da Costa Nunes Isabelle Karine, Araujo Josenildo Segundo Chaves, da Silva Jaqueline Soares, Trachez Margarete Manhães, da Silva Tiago Fernandes, da Costa Filipe P, Sudo Roberto Takashi, Barreiro Eliezer J, Lima Lídia Moreira
机构信息
National Institute of Science and Technology on Drugs and Medicines, Federal University of Rio de Janeiro, Laboratory of Evaluation and Synthesis of Bioactive Compounds, Center of Health Sciences, Rio de Janeiro, Brazil; Program of Research in Drug Development, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Program of Research in Drug Development, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
出版信息
Drug Des Devel Ther. 2016 Sep 9;10:2869-2879. doi: 10.2147/DDDT.S108327. eCollection 2016.
Neuropathy is a serious complication of diabetes that has a significant socioeconomic impact, since it frequently demands high levels of health care consumption and compromises labor productivity. Recently, LASSBio-1471 (3) was demonstrated to improve oral glucose tolerance, reduce blood glucose levels, and display an anti-neuropathy effect in a murine streptozotocin-induced diabetes model. In the present work, we describe the design, synthesis, solubility, plasma stability, and pharmacological evaluation of novel sulfonylhydrazone derivatives (referred to herein as compounds 4-9), which were designed by molecular modification based on the structure of the prototype LASSBio-1471 (3). Among the compounds tested, better plasma stability was observed with 4, 5, and 9 in comparison to compounds 6, 7, and 8. LASSBio-1773 (7), promoted not only hypoglycemic activity but also the reduction of thermal hyperalgesia and mechanical allodynia in a murine model of streptozotocin-induced diabetic neuropathic pain.
神经病变是糖尿病的一种严重并发症，具有重大的社会经济影响，因为它经常需要高水平的医疗保健消费并损害劳动生产率。最近，在小鼠链脲佐菌素诱导的糖尿病模型中，LASSBio-1471（3）被证明可改善口服葡萄糖耐量、降低血糖水平并显示出抗神经病变作用。在本研究中，我们描述了新型磺酰腙衍生物（本文称为化合物4-9）的设计、合成、溶解性、血浆稳定性和药理学评价，这些衍生物是基于原型LASSBio-1471（3）的结构通过分子修饰设计的。在所测试的化合物中，与化合物6、7和8相比，化合物4、5和9表现出更好的血浆稳定性。LASSBio-1773（7）不仅在链脲佐菌素诱导的糖尿病性神经病理性疼痛小鼠模型中具有降血糖活性，还能减轻热痛觉过敏和机械性异常性疼痛。
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