Background: One of the leading global metabolic diseases marked by insulin resistance and chronic hyperglycemia is type 2 diabetes mellitus (T2DM). Since the last decade, DPP-4 enzyme inhibition has proved to be a successful, safe, and well-established therapy for the treatment of T2DM. Objective: The present work reports the synthesis, characterization, and screening of some novel 2-methyl-N'-[(Z)-substituted-phenyl ethylidene] imidazo [1, 2-a] pyridine-3-carbohydrazide derivatives as DPP-IV inhibitors for the treatment of T2DM. Methods: The molecular docking was performed to study these derivatives' binding mode in the enzyme's allosteric site. All the synthesized compounds were subjected for DPP-IV enzyme assay and in vivo antihyperglycemic activity in STZ-induced diabetic rats. Results: The synthesized derivatives exhibited potent antidiabetic activity as compared to the standard drug Sitagliptin. Out of sixteen compounds, A1, A4, B4, C2, C3, and D4 have shown promising antidiabetic activity against the DPP-IV enzyme. The most promising compound, C2, showed a percentage inhibition of 72.02±0.27 at 50 µM concentration. On the 21st-day compound, C2 showed a significant reduction in serum blood glucose level, i.e., 156.16±4.87 mg/dL, then diabetic control, which was 280.00±13.29 mg/dL whereas, standard Sitagliptin showed 133.50±11.80 mg/dL. In the in vivo antihyperglycemic activity, the compounds have exhibited good hypoglycemic potential in fasting blood glucose in the T2DM animal model. All the docked molecules have exhibited perfect binding affinity towards the active pocket of the enzyme. The synthesized derivatives were screened through Lipinski's rule of five for better optimization, and fortunately, none of them had violated the rule. Conclusion: The above results indicates that compound C2 is a relatively active and selective hit molecule that can be structurally modified to enhance the DPP-IV inhibitor's potency and overall pharmacological profile. From the present work, it has been concluded that substituted pyridine-3-carbohydrazide derivatives possess excellent DPP-IV inhibitory potential and can be better optimized further by generating more in vivo, in vitro models.

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Diabetes is a disorder which is characterized by increase in blood glucose level beyond normal value. Now days it is a metabolic disorder and considered as one of the major cause for the death of patients worldwide. Hence there is always a need for the development of newer scaffolds which are useful in treatment of diabetes. In the research computational chemistry plays an important role to discover new possible medicines. In this work, docking analysis has been carried out to study the effects of substituted pyrimidin-2-one on Dipeptidyl peptidase-4 (DPP4). Docking study shows that compound A5 having 2,4-difluorophenyl and 2-hydroxy phenyl group has a potent (IC50 28.13 µM), selective and in vitro efficacious DPP-4 inhibitor. Further molecular modeling revealed compound A5 can fit in the enzyme pocket topologically very well with the pyrimidin-2-one moiety providing hydrogen bond interaction with Glu 205 and Ser 209 of DPP-4. Based on these results, compound A5 might be a promising lead compound for further optimization in the treatment of T2DM.

Thiadiazoles are synthesized by using aromatic acids and thiosemicarbazide. Schiff base reaction is followed and then thiadiazolotriazole derivatives are prepared by using hydrazine hydrate, isoniazid and unhydrous FeCl3. All the synthesized compounds were characterized by IR, 1H-NMR and CHN analyses. All the compounds were evaluated for antibacterial, antifungal & antitubercular activity. Compounds A1,B1, C1 and C4 have shown promising antibacterial activity, compounds A3, A4, B4, C2 and C4 have exhibited excellent antifungal activities, while compounds A2, A4, B2, B4, C2 and C4 showed anti-tubercular activity.

1, 3, 4-oxadiazoles were synthesized by treating pyrazine-2-carbohydrazide with CS2 and alc. KOH and their derivatives were prepared by using R-Cl compounds. pyrazolones were synthesized by treatingpyrazine-2-carbohydrazide with ethyl acetoacetate. The derivatives of pyrazolone were prepared by refluxing pyrazolone with formaldehyde and different substituted secondary amines. All the synthesized compounds were characterized by IR, 1H-NMR and elemental analysis and evaluated for antibacterial, antifungal and antitubercular activities.