br Introduction Diabetes is a common life

Introduction Diabetes is a common life-long health condition and a serious complex condition which can affect the entire body. In the last decade, the cases of people living with diabetes jumped almost 50 percent and worldwide, it afflicts more than 380million people. Dipeptidyl peptidase-IV (DPP-4) inhibitors, a newly emerging drug class for the treatment of type 2 diabetics. Dipeptidyl peptidase IV (DPP-4) is a protease enzyme which inactivates incretin hormones (Glucagon-like peptide 1 (GLP-1) and Alisol B 23-acetate dependent insulin tropic polypeptide (GIP)). Inhibiting DPP-4 prolongs the action of GLP-1 and GIP therefore DPP-4 inhibitors play important roles in maintaining glucose homeostasis [1]. Although the in vivo function of other members of DPP family, that is DPP-2, DPP-8, DPP-9 etc. are largely unknown the physiological effects of their inhibition has been documented in literature [2]. A number of catalytically active DPPs distinct from DPP-4 (DPP 2, FAP, DPP-8 and DPP-9) have been described that is associated with side-effects and toxicity [3]. Undergoing clinical trials on diabetic patients confirmed DPP-4 inhibitors as an add-on drug to oral hypoglycemic agents in type 2 diabetes. Sitagliptin was the first DPP-4 inhibitor granted by US-FDA for treating patients with type 2 diabetes followed by Vildagliptin, Saxagliptin and Linagliptin (Fig. 1) [4], [5]. Omarigliptin (MK-3102) (approved in Japan in 2015) can be used as once-weekly treatment and generally well-tolerated throughout the base and extension studies [6]. Similarly synthetic analogs of Alogliptin by replacing the cyanobenzyl group with the butynyl group have been synthesized and tested as selective DPP-4 inhibitors [7], [8]. Additionally, quinazolines [9], [10], pyridopyrimidinediones [11], pyrazolopyrimidinones [12] and pyrimidines [13] as DPP-IV inhibitors are of particular interest for diabetics. Furthermore, various quinazoline and thiazoline analogs have been proved to be effective antidiabetic agents (Fig. 2) [14], [15], [16]. From the literature it has been found that quinazoline and thiazoline analogs (Fig. 3) also have antioxidant activity [17], [18], [19]. Quinazoline clubbed thiazolines have also been proved to show antioxidant and antidiabetic activity (Fig. 2, Fig. 3) [20], [14]. In view of these results, we have observed that substituted quinazolines are worthy of further studies and aiming at finding new structures, which could be a lead in the field of diabetics, therefore we have planned to synthesize new molecules, quinazolines endowed with thiazoline nuclei, in an attempt to significantly improve the antidiabetic activity. Therefore, several molecules were design, synthesize and screened for their DPP-4 inhibition activity, in vivo antidiabetic activity and also evaluated for their DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity. Further, molecular docking studies were also carried out to identify their possible binding mode within the catalytic domain of DPP-4 enzyme.