Vinay Bharadwaj Tatipamula1, Murali Krishna Kolli2, Surendra Babu Lagu3, Karuna Raman Paidi2, Raveendra Reddy P2, Rajendra Prasad Yejella3. 1. Pharmaceutical Chemistry Department, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, 530 003, Andhra Pradesh, India. Electronic address: tvinaybharadwaj@andhrauniversity.edu.in. 2. Department of Chemistry, Sri Krishnadevaraya University, Ananthapuramu, 515 003, Andhra Pradesh, India. 3. Pharmaceutical Chemistry Department, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, 530 003, Andhra Pradesh, India.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: Among all synthetic derivatives, compound 12 showed good inhibitory profile against DPPH, superoxide free radicals and α-glucosidase enzyme with half maximal inhibitory concentration (IC50) 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. CONCLUSION: Our data suggest that the indolizine derivatives can be a benchmarks for designing potent oral antidiabetic agents.
BACKGROUND: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 humandiabetes. The present study investigated the effects of novel indolizine derivatives (1-16) on plasma blood glucose concentrations in STZ-diabeticrats. METHODS: 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 diabeticrats. RESULTS: Among all synthetic derivatives, compound 12 showed good inhibitory profile against DPPH, superoxide free radicals and α-glucosidase enzyme with half maximal inhibitory concentration (IC50) 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 diabeticrats with respect to the standard. Furthermore, 21 days of successive treatment with compound 12 in diabeticrats 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. CONCLUSION: Our data suggest that the indolizine derivatives can be a benchmarks for designing potent oral antidiabetic agents.
Authors: Ekaterina A Sokolova; Alexey A Festa; Karthikeyan Subramani; Victor B Rybakov; Alexey V Varlamov; Leonid G Voskressensky; Erik V Van der Eycken Journal: Molecules Date: 2020-09-05 Impact factor: 4.411