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  • br Acknowledgments The financial support from the National N

    2022-05-13


    Acknowledgments The financial support from the National Natural Science Foundation of China (Nos. 31460422 and 31060210), the Natural Science Foundation of Jiangxi Province, China (20171BAB204029 and 20143ACB20006), the Project of Science and Technology of Jiangxi Provincial Education Department, China (GJJ150187), and the Research Project of State Key Laboratory of Food Science and Technology (SKLF-ZZB-201707, SKLF-ZZA-201612 and SKLF-KF-201607) is gratefully acknowledged.
    Introduction α-Glucosidase (EC 3.2.1.20) as a catabolic enzyme hydrolyzes carbohydrates Hydroxysafflor yellow A to produce energy metabolic sugars essential for normal physiological functions [1]. α-Glucosidase providing energy sources to maintain healthy functioning. In contrast, glucose Hydroxysafflor yellow A in patients with type-2 diabetes can cause clinically serious problems because high activity of this enzyme increases plasma mellitus glucose levels. Numerous reports address the relevance of α-glucosidase inhibition and the regulation of glucose levels in type-2diabetes mellitus by α-glucosidase inhibitors [2], [3], [4]. Several types of α-glucosidase inhibitors have been clinically applied to inhibit α-glucosidase for medicinal purposes including acarbose, voglibose and miglitol [5], [6]. Inhibitors of this enzyme are designed to be orally taken, acting as an anti-diabetic drug by preventing the digestion of carbohydrates and by delaying the absorption of sugar. This allows plasma glucose to be maintained at a steady level. However due to numerous side effects of these drugs, medicinal chemists are continuously in struggles to discover new alpha glucosidase inhibitors. In this regard we have synthesized benzothiazole based oxadiazole derivatives (see-Fig. 1.). The benzothiazoles are heterocyclic compounds with diverse range of biologically activity [7], [8]. It shows numerous activities such as antimicrobial, antitumor, anti-inflammatory, antilieshmanial and antifungal [9], [10], anticancer [11], antidiabetic [12], anticonvulsant [13], antiviral [14], antitubercular [15], antimalarial [16], antihelmintic [17], analgesic [18] and fungicidal activities [19]. Recently, benzothiazole derivatives have been evaluated as potential amyloid-binding diagnostic agents in neurodegenerative disease [20]. The1,3,4-oxadiazole constitute an important class of compounds in medicinal and pharmaceutical chemistry. The compounds containing 1,3,4-oxadiazole nucleus possess a vast spectrum of biological activities [21]. Recently, differently substituted 1,3,4-oxadiazoles have been reported for their biological activities, such as antibacterial [22], antifungal [23], insecticidal [24] antiviral [25] inflammatory [26] antitubercular [27] antitumoral [28], anticancer [29] and analgesic activity [30] (see- Fig. 2.). Our group has synthesized and screened benzothiazole esters and hydrazide for α-glucosidase potential. These analogs were found to have best activity [31]. Based on that, we have decided to synthesize benzothiazole linked oxadiazole derivatives 1–23 for α-glucosidase inhibition.
    Experimental
    Results and discussion
    Conclusion Benzothiazole based oxadiazole derivatives (1–23) have been synthesized and evaluated for α-glucosidase inhibitory potential.All derivatives displayed potent α-glucosidase inhibitory potential ranging between0.5 ± 0.01–30.90 ± 0.70 µM as a compare to acarbose. The dihydroxy analogs were found to be the most potent among the series. Molecular docking revealed HOX genes the top ranked conformations of almost all compounds were well accommodated inside the active site of α-glucosidase enzyme and were involved in various types of interactions with the active site residues of α-glucosidase enzyme.
    Acknowledgment Higher Education commission of Pakistan for financial support under the National Research Program for Universities, project number 5721.