Pharmaceutical Chemistry Department, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, 530 003, Andhra Pradesh, India.
Department of Chemistry, Sri Krishnadevaraya University, Ananthapuramu, 515 003, Andhra Pradesh, India.
Pharmacol Rep. 2019 Apr;71(2):233-242. doi: 10.1016/j.pharep.2018.11.004. Epub 2018 Nov 28.
Diabetes mellitus is a deadly disorder in human which induce chronic complications. The streptozotocin (STZ)-induced diabetes in rat is the most common animal model of human diabetes. The present study investigated the effects of novel indolizine derivatives (1-16) on plasma blood glucose concentrations in STZ-diabetic rats.
In vitro experiments were performed on 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide free radicals, α-glucosidase enzyme and in vivo studies on normal, oral glucose loaded and STZ-induced diabetic rats.
Among all synthetic derivatives, compound 12 showed good inhibitory profile against DPPH, superoxide free radicals and α-glucosidase enzyme with half maximal inhibitory concentration (IC) values of 56.2, 33.5 and 26.5 μg/mL, respectively. The lethal dosage of indolizine derivatives was found to be above 1000 mg/kg body weight (b.w.). From the in vivo studies, it can be determined that the compound 12 depicted pronounced protective hypoglycemic effects in normal, glucose-loaded and STZ-induced diabetic rats with respect to the standard. Furthermore, 21 days of successive treatment with compound 12 in diabetic rats exhibited better recovery of body weight and considerable variations in biochemical parameters as that of the standard drug. Moreover, the histopathological section of pancreas and testes justifies the rehabilitation and regeneration of islets, acini and Sertoli cells in animals treated with compound 12.
Our data suggest that the indolizine derivatives can be a benchmarks for designing potent oral antidiabetic agents.
糖尿病是一种严重的人类疾病，会引起慢性并发症。链脲佐菌素（STZ）诱导的大鼠糖尿病是人类糖尿病最常见的动物模型。本研究旨在探讨新型吲哚嗪衍生物（1-16）对 STZ 糖尿病大鼠血糖浓度的影响。
在体外实验中，对 1,1-二苯基-2-苦基肼（DPPH）、超氧自由基、α-葡萄糖苷酶进行了实验，在正常、口服葡萄糖负荷和 STZ 诱导的糖尿病大鼠中进行了体内研究。
在所合成的衍生物中，化合物 12 对 DPPH、超氧自由基和α-葡萄糖苷酶表现出良好的抑制作用，其半数最大抑制浓度（IC）值分别为 56.2、33.5 和 26.5μg/mL。吲哚嗪衍生物的致死剂量被发现大于 1000mg/kg 体重（b.w.）。从体内研究可以看出，与标准药物相比，化合物 12 在正常、葡萄糖负荷和 STZ 诱导的糖尿病大鼠中表现出明显的保护降血糖作用。此外，在糖尿病大鼠中连续 21 天用化合物 12 治疗，体重恢复较好，生化参数变化明显，与标准药物相当。此外，胰腺和睾丸的组织病理学切片证明了用化合物 12 治疗的动物胰岛、腺泡和支持细胞的修复和再生。
我们的数据表明，吲哚嗪衍生物可以作为设计有效的口服抗糖尿病药物的基准。
