br Results and discussion br Conclusion In conclusion we des

Results and discussion
Conclusion In conclusion, we designed and synthesized a novel series of thiosemicarbazide-1,2,3-triazole hybrids 10a-o. Further, α-glucosidase inhibitory activity of the synthesized compounds 10a-o was evaluated. The obtained results showed that all the synthesized thiosemicarbazide-1,2,3-triazole hybrids are more potent than standard drug acarbose. Kinetic study of the most potent compound 10h indicated that it competitively inhibited α-glucosidase. Furthermore, docking study showed that selected compounds 10b, 10h, and 10m interacted with important residues in the active site of α-glucosidase. In summary, the results have shown that these thiosemicarbazide-1,2,3-triazole hybrids are a new class of α-glucosidase inhibitors.
Acknowledgements This research has been supported by a grant from the Research Council of Tehran University of Medical Sciences (Grant No. 98-01-192-41780).
Introduction Diabetes mellitus (DM) is a kind of metabolic disorder disease, which is characterized by high blood glucose levels. DM constitutes a worldwide public health problem that affected 451 million people aged 19–99 years in 2017, and the number may grow to 693 million by 2045 [1]. The rising prevalence of diabetes results from rapid urbanization, nutrition transition and increasingly sedentary lifestyles [2]. Persistently DM causes a rise in incidence of secondary comorbidities including cardiomyopathy [3], neuropathy [4], nephropathy [5], and retinopathy [6]. Furthermore, the death caused by diabetes approximately 5 million worldwide in the 20–99 years age range and the expenditure with diabetes was USD 850 billion in 2017 [1]. Therefore, it is urgent to explore effective therapy methods for DM. α-glucosidase is a key enzyme in the brush border of the enterocytes of the jejunum, which catalyzes the hydrolysis of oligosaccharide and disaccharide into monosaccharide to promote the Thiomyristoyl of glucose [7]. The α-glucosidase inhibitor can delay the absorption of glucose by the gastrointestinal tract, decrease the postprandial increase in plasma glucose, and result in lower postprandial plasma insulin levels [8]. The decrease of plasma glucose not only releases the strain on the β-cell, but also helps manage the diabetes [9], [10]. Some α-glucosidase inhibitors currently serve as first-line therapy in combination with sulfonylureas or insulin, such as acarbose, voglibose and miglitol [11]. Nevertheless, α-glucosidase inhibitors from organic synthesis show many side effects, such as flatulence, diarrhea, and acute hepatitis [12], [13], [14]. Thus, many studies are being conducted to search for effective, low-toxic and low-cost α-glucosidase inhibitors from natural resources. For the past few years, many natural resources had been proved to have the ability to inhibit α-glucosidase. Zhang L. et al found that the extractions of two Acer palmatum cultivars(Acer palmatum Atropurpureum and Acer palmatum Thunb), Ipomoea batatas leaf and jackfruit peel showed strong α-glucosidase inhibitory activity [15], [16], [17]. Bai and Lee revealed leaves of Vigna angularis have significant α-glucosidase inhibitory activities [18], [19]. Meantime, many kinds of compounds from natural sources showed inhibitory activity against α-glucosidase, such as flavonol, flavonoid glycoside and lignin [20], [21], [22]. Seeds of Vigna angularis (Willd.) Ohwi & Ohashi is one of the most popular edible beans around the world, especially in East Asia countries. It also serves as a traditional medicine for its diuretic action, detoxification properties in China [23]. Recently, many researches indicated that extractions from Vigna angularis showed lots of physiological activities, such as antioxidant, anti-obesity and hepatoprotective [24], [25], [26]. Because of the huge demand for Vigna angularis, its stem and leaf are abundant byproducts worldwide. As mention above, the leaves of Vigna angularis have α-glucosidase inhibitory activities. Nevertheless, Vigna angularis leaf is difficult to obtain because of natural shedding during ripening and mechanical harvesting. Considering the similarity of ingredients in different parts of plant, this study focused on the α-glucosidase inhibitor and antioxidant activity of VAS, the main byproduct after harvest. To date, few research is about the ingredients having antioxidant and α-glucosidase inhibitory activity in VAS.