Executive Summary : | Diabetes Mellitus (DM) is a complex disorder characterized by insulin deficiency, decreased insulin sensitivity, and other factors leading to vascular and metabolic abnormalities. It is a leading cause of death and can be treated with drugs like α-glucosidase inhibitors, biguanides, sulfonylureas, thiazolidinedione, and gliptins. However, these drugs have biological efficacy and some side effects, making it urgent to develop new potent anti-diabetic agents with minimal side effects. Fluoro- or trifluoromethyl substituted heterocylic derivatives are prime candidates for developing new drugs, especially six- or five-membered ring derivatives. Heterocyclic moieties like enaminone-based pyrimidine, pyrazole, benzimadazole, quinolone-based Azetidinone, and thiazolidinone substituted with fluoro or trifluoromethyl groups are effectively utilized as intermediates for the development of active synthetic compounds with a wide range of pharmacological activity. The proposed research aims to design, synthesize, and evaluate the anti-diabetic activity of new fluoro or trifluoromethyl substituted enaminone-based pyrimidine derivatives, 2-Azetidinone derivatives, 2-thiazolidinone derivatives, quinolone schiff bases, 2-Azetidinone derivatives, and 4-thiazolidinone derivatives. The titled derivatives will be designed and screened for anti-diabetic activity using in silico docking studies using PyRx virtual docking software 0.8, and validated by an in vitro Dipeptidyl Peptidase IV (DPP-IV) assay and an in vivo method. The in vitro anti-diabetic activity can be evaluated by determining % inhibition or IC50 values, while the in vivo anti-diabetic activity can be evaluated by determining fasting blood glucose level, bodyweight variation, oxidative stress-related parameters, and histopathological studies. |