Transition Metal Substituted Polyoxometalates as α‐Glucosidase Inhibitors

Abstract

α‐Glucosidase inhibitors slow the digestion of carbohydrates and reduce blood sugar levels after meals. Recently, our experimental team found that phosphomolybdic acid with a Dawson‐type structure can effectively inhibit the activity of α‐glucosidase. Dawson‐type phosphomolybdic acid {H6(P2Mo18O62), H8[P2Mo17Fe(OH2)O61], H8[P2Mo17Co(OH2)O61] and H8[P2Mo17Ni(OH2)O61] abbreviated as P2Mo18, P2Mo17Fe, P2Mo17Co and P2Mo17Ni} were synthesized, and their inhibitory potential for α‐glucosidase was evaluated by enzyme kinetic analysis and molecular docking techniques. The results of kinetic analysis showed that P2Mo18, P2Mo17Fe, P2Mo17Co and P2Mo17Ni had a good inhibitory effect on α‐glucosidase, and the inhibitor concentration values of 50 % reduction in activity were 0.174 ± 0.0146 µm, 0.504 ± 0.00507 mm, 0.402 ± 0.00381 mm, 0.293 ± 0.0137 mm, respectively. Among them, P2Mo18, P2Mo17Co and P2Mo17Ni showed reversible mixed inhibition on α‐glucosidase, and P2Mo17Fe showed reversible competitive inhibition on α‐glucosidase. In addition, the four compounds separately form non‐covalent interactions with the enzyme molecule, including hydrogen bonds formed, wan der vaals interactions. This result is consistent with the mechanism study of enzyme kinetics. Overall, our results indicate that Dawson‐type parent P2Mo18 and three transition‐metal‐substituted phosphomolybdic acids P2Mo17Fe, P2Mo17Co and P2Mo17Ni are very promising as α‐glucosidase inhibitors for the treatment of diabetes.

Nineteen New Flavanol–Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from Amomum tsao-ko

“…As a comparison, both K m and V max values of compounds 2 and 6 decreased with the increment of concentration. From the abovementioned analysis, they were deduced as mixed-type inhibitors against α-glucosidase. , By the secondary plots of the slope and intercept versus concentrations, their K i values (the inhibition constant of the free enzyme) were calculated as 13.0, 11.7, 2.9, and 5.3 μM and K is values (the inhibition constant of the enzyme–substrate complex) were 21.5, 4.1, 1.2, and 54.6 μM. The K is values of 1 and 11 were larger than their K i values, indicating the priority in binding with the free enzyme.…”

Mechanism of melanogenesis inhibition by Keggin-type polyoxometalates

“…[28][29][30] More intriguingly, one of the important biological applications of POMs is their ability to cause the inhibition of certain enzymes. 31 Our group has previously confirmed that Keggin-type POMs can be excellent inhibitors of α-glucosidase [32][33][34] and tyrosinase [35][36][37][38] , and, among them, H 3 PMo 12 O 40 possesses the strongest inhibitory effect on these two enzymes. However, it remains unclear whether Keggin-type POMs will exhibit optimal effects in vivo.…”

Study on the Regulation and Mechanism of the Vanadium Substituted Polyoxometalates of H6[P2Mo18O62] on Melanogenesis of Mouse Melanoma Cell B16

“…多金属氧酸盐(简称多酸)是由氧原子桥接的 d 0 或 d 1 金属离子组成的过渡金属氧化物簇, 由处于最高氧化状 态的早期过渡金属元素(Mo、 W、 V、 Nb 等)组成 [23][24] . 由 于其独特的形状和负表面电荷 [25][26][27][28] , 多酸通过共价键、 氢键和范德华力特异性地结合到各种生物分子上, 从而 发挥其生物活性 [29][30][31] , 过去几十年中, 多酸被用于治疗 炎症性肠病 [32] 、皮肤色素沉着 [33][34] 、肿瘤 [35][36][37][38] 、流感 [39] 和艾滋病毒 [40] 、糖尿病 [41] 、哮喘 [42] 、急性肾损伤 [43] 、 脑缺血/再灌注损伤 [44] , 甚至阿尔茨海默病 [45][46][47] . 先前 的研究发现, 多酸在体外对酪氨酸酶具有良好的抑制作 用 [48][49] [50][51] 一致.…”