br Acknowledgements This research was funded by

Acknowledgements This research was funded by Ministry of Education Malaysia (MOE), and supported by the Department of Nutrition, Exercise & Sports, Department of Drug Design, University of Copenhagen, Denmark and Universiti Malaysia Pahang (UMP), Malaysia. HPLC equipment used for high-resolution bioassay profiles was obtained from the Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Introduction Type 2 diabetes, the main type of diabetes mellitus (DM), is currently recognized as a serious global health problem. Type 2 diabetes is a type of noninsulin-dependent diabetes caused by insulin deficiency or insulin resistance [1,2]. α-Glucosidase is a carbohydrate hydrolase, and the inhibition of its activity may delay the digestion of Rifapentine and thereby reduce the amount of glucose absorbed into the blood [3,4]. Thus, α-glucosidase is considered to be an important target for the treatment of noninsulin-dependent diabetes mellitus and for the design of many α-glucosidase inhibitors [5]. At present, the research of domestic and foreign scholars on α-glucosidase inhibitors mainly focuses on natural extracts and organic compounds. Jang et al. [6] reported that scopoletin might contribute to relieving postprandial hyperglycemia through the inhibition of carbohydrate digestive enzymes. Ding et al. [7] designed and synthesized a series of novel oxazolxanthones that showed good inhibition of α-glucosidase by studies of enzyme kinetics and molecular docking. However, few inorganic agents capable of inhibiting α-glucosidase have been reported. In addition, high efficiency, low cytotoxicity and low cost are the key factors to be considered in the design of α-glucosidase inhibitors. Herein, current therapeutic drugs (acarbose, voglibose and miglitol) have been used clinically for many years, but the clinical application of these compounds has always been limited by their high cost and side effects [8]. Therefore, designing novel, safe and effective α-glucosidase inhibitors is an attractive goal in the field of medicinal chemistry. Polyoxomolybdates (abbreviated as POMs), due to their incomparable structural diversity and novel functional properties, have been widely studied in various fields (Table S1), such as catalysis [[9], [10], [11]], medicine [12,13], material science [14,15], photoelectrochemistry [16,17] and self-assembled nanozymes [13,18]. Especially in the field of medicine, POMs are promising candidates for drug-carrier approaches on the path to the identification of new composite drugs because genetic drift have long been known for their multifaceted bioactivities that encompass anticancer, anti-tumor, antiviral and antibacterial effects [[19], [20], [21], [22], [23]]. Furthermore, the inhibitory effect of POMs on various enzyme activities has become a hotspot for research and the development of safe, nontoxic and high-efficiency enzyme inhibitors for POM properties has escalated in recent years. Many studies have demonstrated that POMs possess significant inhibitory effects on the activities of nucleotidases, phosphatases, kinases, sulfotransferases, sialyltransferases, acetylases, nucleases and proteases [24,25]. Gumerova et al. [26] analyzed and compared the inhibitory effects of nine different polyoxotungstates (POTs) on two P-type ATPases, and the results reveal the high potential of some POTs to act as P-type ATPase inhibitors, with K9(C2H8N)5[H10Se2W29O103] showing high selectivity towards Ca2+-ATPase. Lee et al. [27] evaluated the inhibitory potency of a series of POMs as well as chalcogenide hexarhenium cluster complexes against a broad range of ecto-nucleotidases, and the [Co4(H2O)2(PW9O34)2]10−(5, PSB -POM 142) was discovered to be the most potent inhibitor of human NTPDase1. Moreover, in comparison to mononuclear complexes, POMs have been markedly under-studied in the context of diabetes [23,28]. Ilyas et al. [29] evaluated the inhibitory effects of different polytungstates on glucosidases (α- and β) in vitro and in vivo, and the research showed that Na20[P6W18O79]·37H2O (Na-P6W18) was the most potent inhibitor of α-glucosidase (IC50 = 1.33 ± 0.41 μM). Although some functionalized POMs have been used as inhibitors of α-glucosidase, their molecular mechanism of action is largely unknown. As a result of insightful studies on POMs for α-glucosidase, compounds with improved pharmacological properties might be developed for the treatment of diabetes. Furthermore, Keggin-type POMs and their derivatives exhibit better biological activities and lower cytotoxicities [[30], [31], [32]] and may become potentially effective enzyme inhibitors.