Study on the Antioxidant Properties of Polyoxometalates α-Glucosidase Inhibitors

doi:10.6023/A23060276

Abstract

Three types of Dawson type phosphomolybdate were synthesized and the in vitro antioxidant properties of the 11 compounds were investigated by the scavenging effect of different concentrations of polyoxometalates (0~50 mg/mL with distilled water and Vitamin C (VC) as positive control, three parallel experiments were set up for each group) on 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, hydroxyl radicals, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and superoxide anion radicals. The cytotoxicity of the compounds was assayed by methyl thiazolyl tetrazolium (MTT) assay and combined with the results of in vitro antioxidant and cytotoxicity assays, cellular antioxidant studies were performed on H₆[P₂Mo₁₈O₆₂], H₇[P₂Mo₁₇VO₆₂] and H₈[P₂Mo₁₆V₂O₆₂] using HepG2 cells as a model. The total intracellular antioxidant capacity was measured using the ABTS method: 10 μL of the sample/standard solution and 200 μL of the ABTS working solution were mixed in a 96-well plate for 5 min at room temperature, and the absorbance of the sample was measured at 734 nm using a multifunctional enzyme marker. WST-1 assay for cellular superoxide dismutase (SOD) activity: The samples to be tested were diluted to different concentrations and the absorbance values were measured at 450 nm using a multifunctional enzyme marker. The SOD inhibition rate of the sample to be tested was calculated and a sample concentration of 40%~60% inhibition was selected for the experiment. Cellular antioxidant assays showed that H₆[P₂Mo₁₈O₆₂] had a total cellular antioxidant capacity comparable to that of VC at higher concentrations (25 μmol/L and above); it enhanced the activity of cellular superoxide dismutase (SOD) and was more active than VC. We investigated the interaction mechanisms of molecular docking between polyoxometalates and α-glucosidase. The results showed that all 11 compounds had good antioxidant properties, and molecular docking showed that the binding inhibition of the polyoxometalates to the amino acid residues in the active centre was reversible mainly through hydrogen bonding and van der Waals forces, and that the docking fraction was negative and the reaction could proceed spontaneously, but the types of amino acids involved varied. Among them, H₆[P₂Mo₁₈O₆₂], H₈[P₂Mo₁₇Fe(OH₂)O₆₁], H₈[P₂Mo₁₇Ni(OH₂)O₆₁], H₇[P₂Mo₁₇VO₆₂] and H₈[P₂Mo₁₆V₂O₆₂] performed well and could be alternative materials for antioxidants with both α-glucosidase inhibiting effect.

Key words: polyoxometalates, molecular docking, α-glucosidase, antioxidation, reactive oxygen species

Cite this article

Yao Li, Bingnian Chen, Dan Luo, Shan Lei, Li Wang. Study on the Antioxidant Properties of Polyoxometalates α-Glucosidase Inhibitors[J]. Acta Chimica Sinica, 2023, 81(10): 1318-1326.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 6

Figure 1. (a) ABTS radical scavenging ability of Dawson type phosphomolybdate with different transition metal substitutions. (b) DPPH radical scavenging ability of Dawson type phosphomolybdate with different transition metal substitutions. (c) Hydroxyl radical scavenging ability of Dawson type phosphomolybdate with different transition metal substitutions. (d) Hydroxyl radical scavenging ability of Dawson type phosphomolybdate with different number of vanadium substitutions. (e) Superoxide anion radical scavenging ability of Dawson type phosphomolybdate with different transition metal substitutions. (f) Superoxide anion radical scavenging ability of Dawson type phosphomolybdate with different number of vanadium substitutions

Figure 2. (a) Effects of different transition metal substitutions of Dawson type phosphomolybdate on the survival rate of HepG2 cells. (b) Effects of Dawson type phosphomolybdate substituted with different amounts of vanadium on the survival rate of HepG2 cells. Compared with the control group, * means significant difference (p<0.05), *** means extremely significant difference (p<0.001), **** means extremely significant difference (p<0.0001)

Figure 3. (a) Total antioxidant capacity of Dawson type phosphomolybdic acid parent. a and b represent significant differences among different groups. (b) Total antioxidant capacity of P2Mo17V and P2Mo16V2. a, b and ab represent significant differences among different groups. (c) SOD activity of Dawson type phosphomolybdate parent. The relative activity of SOD in P2Mo18 treated cells was calculated by setting the enzymatic activity of control (solvent distilled water) as 1.0. a, b, c and ab represent significant differences among different groups. (d) SOD activity of P2Mo17V and P2Mo16V2. The relative activity of SOD in cells treated with P2Mo17V and P2Mo16V2 was calculated by setting the enzymatic activity of control (solvent distilled water) as 1.0. a, b, c and ab represent significant differences among different groups

Figure 4. Binding mode of P2Mo17Fe to the active site of α-glucosidase

化合物	氢键和金属键相关氨基酸	氢键数量	对接分数/ (kJ•mol^－1)
P₂Mo₁₇Fe	Arg442, Arg446, Arg315, Arg213, Gln353, Gln279, Asn350, Asp307, Asp215, Asp69, Glu411	17	－122
P₂Mo₁₇Co	Asp215, Asp69, Asp352, Arg442, Arg446, Arg315, Arg213, Gln279, Glu411, Glu277, Tyr72, Tyr316, His315, His112, Asn350	14	－116
P₂Mo₁₇Ni	Asp215, Asp69, Asp352, Arg307, Arg446, Arg315, Arg213, Tyr72, Tyr316, His315, His112, Asn350, Gln353, Gln279	18	－118
P₂Mo₁₇V	Ser240, Asp307, Asp242, Gln279, Tyr158, Arg315, His280	7	－131
P₂Mo₁₆V₂	Phe159, Phe178, Phe303, Val216, Val109, Leu219, Tyr316, Asp215, Asp69, His112, Gln353, Gln279, Gln182, Arg315, Arg213, Arg446	10	－134
P₂Mo₁₄V₄	Glu277, Gln353, Gln279, Asp215, Asp69, Asp352, Arg315, Arg213, Arg446, Asn350	12	－126
P₂Mo₁₃V₅	Asp215, Asp69, Asp307, Glu277, Gln353, Gln279, His351, Arg315, Arg213, Arg446, Asn350	14	－122

Table 1. Docking effects of P2Mo17Fe, P2Mo17Co, P2Mo17Ni, P2Mo17V, P2Mo16V2, P2Mo14V4, P2Mo13V5 with α-glucosidase

	对照孔	对照空白孔	测定孔	测定空白孔
待测样本/μL	—	—	20	20
蒸馏水/μL	20	20	—	—
酶工作液/μL	20	—	20	—
酶稀释液/μL	—	20	—	20
底物应用液/μL	200	200	200	200

Table 2. SOD activity detection system

References 60

[1]	Bhatti, J. S.; Sehrawat, A.; Mishra, J.; Sidhu, I. S.; Navik, U.; Khullar, N.; Kumar, S.; Bhatti, G. K.; Reddy, P. H. Free Radic. Biol. Med. 2022, 184, 114. doi: 10.1016/j.freeradbiomed.2022.03.019
[2]	Singh, A.; Kukreti, R.; Saso, L.; Kukreti, S. Molecules 2022, 27, 950. doi: 10.3390/molecules27030950
[3]	Andreadi, A.; Bellia, A.; Di Daniele, N.; Meloni, M.; Lauro, R.; Della-Morte, D.; Lauro, D. Curr. Opin. Pharmacol. 2022, 62, 85. doi: 10.1016/j.coph.2021.11.010
[4]	De Geest, B.; Mishra, M. Antioxidants 2022, 11, 784. doi: 10.3390/antiox11040784
[5]	Yang, J.; Wang, X.; Zhang, C.; Ma, L.; Wei, T.; Zhao, Y.; Peng, X. Food Chem. 2021, 347, 129056. doi: 10.1016/j.foodchem.2021.129056
[6]	Peng, X.; Zhang, G.-W.; Liao, Y.-J.; Gong, D.-M. Food Chem. 2016, 190, 207. doi: 10.1016/j.foodchem.2015.05.088
[7]	Li, H.; Yang, J.-C.; Wang, M.-F.; Ma, X.-Z.; Peng, X. Food Chem. 2023, 420, 136113. doi: 10.1016/j.foodchem.2023.136113
[8]	Cardullo, N.; Muccilli, V.; Pulvirenti, L.; Cornu, A.; Pouysegu, L.; Deffieux, D.; Quideau, S.; Tringali, C. Food Chem. 2020, 313, 126099. doi: 10.1016/j.foodchem.2019.126099
[9]	Wang, X.; Deng, Y.; Xie, P.; Liu, L.; Zhang, C.; Cheng, J.; Zhang, Y.; Liu, Y.; Huang, L.; Jiang, J. Food Chem. 2023, 404, 134481. doi: 10.1016/j.foodchem.2022.134481
[10]	Xu, Y.; Rashwan, A. K.; Ge, Z.; Li, Y.; Ge, H.; Li, J.; Xie, J.; Liu, S.; Fang, J.; Cheng, K.; Chen, W. Food Chem. 2023, 399, 133999. doi: 10.1016/j.foodchem.2022.133999
[11]	Hu, J.-F.; Lai, X.-H.; Wu, X.-D.; Wang, H.-Y.; Weng, N.-H.; Lu, J.; Lyu, M.; Wang, S.-J. Foods 2023, 12, 183. doi: 10.3390/foods12010183
[12]	Tian, T.; Chen, G.; Zhang, H.; Yang, F. Molecules 2021, 26, 4638. doi: 10.3390/molecules26154638
[13]	Dai, T.; Chen, J.; Mcclements, D. J.; Li, T.; Liu, C. Int. J. Biol. Macromol. 2019, 130, 315. doi: 10.1016/j.ijbiomac.2019.02.105
[14]	Chen, X.-Y.; Sun-Waterhouse, D.; Yao, W.-Z.; Li, X.; Zhao, M.-M.; You, L.-J. Food Chem. 2021, 365, 130524. doi: 10.1016/j.foodchem.2021.130524
[15]	Wang, X.-Q.; Wang, W.-J.; Peng, M.-Y.; Zhang, X.-Z. Biomaterials 2021, 266, 120474. doi: 10.1016/j.biomaterials.2020.120474
[16]	Cheung, E. C.; Vousden, K. H. Nat. Rev. Cancer 2022, 22, 280. doi: 10.1038/s41568-021-00435-0
[17]	Murphy, M. P.; Bayir, H.; Belousov, V.; Chang, C. J.; Davies, K. J. A.; Davies, M. J.; Dick, T. P.; Finkel, T.; Forman, H. J.; Janssen-Heininger, Y.; Gems, D.; Kagan, V. E.; Kalyanaraman, B.; Larsson, N.; Milne, G. L.; Nystrom, T.; Poulsen, H. E.; Radi, R.; Van Remmen, H.; Schumacker, P. T.; Thornalley, P. J.; Toyokuni, S.; Winterbourn, C. C.; Yin, H.; Halliwell, B. Nat. Metab. 2022, 4, 651. doi: 10.1038/s42255-022-00591-z
[18]	Juan, C. A.; Perez De La Lastra, J. M.; Plou, F. J.; Perez-Lebena, E. Int. J. Mol. Sci. 2021, 22, 4642. doi: 10.3390/ijms22094642
[19]	Sies, H.; Belousov, V. V.; Chandel, N. S.; Davies, M. J.; Jones, D. P.; Mann, G. E.; Murphy, M. P.; Yamamoto, M.; Winterbourn, C. Nat. Rev. Mol. Cell Biol. 2022, 23, 499. doi: 10.1038/s41580-022-00456-z
[20]	Zhang, C.-Y.; Wang, X.; Du, J.-F.; Gu, Z.-J.; Zhao, Y.-L. Adv. Sci. 2021, 8, 2002797. doi: 10.1002/advs.v8.3
[21]	Kalyane, D.; Choudhary, D.; Polaka, S.; Goykar, H.; Karanwad, T.; Rajpoot, K.; Tekade, R. K. Prog. Mater. Sci. 2022, 130, 100974. doi: 10.1016/j.pmatsci.2022.100974
[22]	Montllor-Albalate, C.; Kim, H.; Thompson, A. E.; Jonke, A. P.; Torres, M. P.; Reddi, A. R. Proc. Natl. Acad. Sci. U. S. A. 2022, 119, e2023328119.
[23]	Hoseinifar, S. H.; Yousefi, S.; Van Doan, H.; Ashouri, G.; Gioacchini, G.; Maradonna, F.; Carnevali, O. Rev. Fish. Sci. Aquac. 2020, 29, 198.
[24]	Lv, R.; Dong, Y.; Bao, Z.; Zhang, S.; Lin, S.; Sun, N. Trends Food Sci. Technol. 2022, 122, 171. doi: 10.1016/j.tifs.2022.02.026
[25]	Rajput, V. D.; Harish; Singh, R. K.; Verma, K. K.; Sharma, L.; Quiroz-Figueroa, F. R.; Meena, M.; Gour, V. S.; Minkina, T.; Sushkova, S.; Mandzhieva, S. Biology-Basel. 2021, 10, 267.
[26]	Kasai, S.; Shimizu, S.; Tatara, Y.; Mimura, J.; Itoh, K. Biomolecules 2020, 10, 320. doi: 10.3390/biom10020320
[27]	Khalil, I.; Yehye, W. A.; Etxeberria, A. E.; Alhadi, A. A.; Dezfooli, S. M.; Julkapli, N. B. M.; Basirun, W. J.; Seyfoddin, A. Antioxidants. 2020, 9, 24. doi: 10.3390/antiox9010024
[28]	Wang, Q.; Cheng, C.-Q.; Zhao, S.; Liu, Q.-Y.; Zhang, Y.-H.; Liu, W.-L.; Zhao, X.-Z.; Zhang, H.; Pu, J.; Zhang, S.; Zhang, H.-G.; Du, Y.; Wei, H. Angew. Chem. Int. Ed. 2022, 61, e202201101.
[29]	Gulcin, I. Arch. Toxicol. 2020, 94, 651. doi: 10.1007/s00204-020-02689-3
[30]	Forman, H. J.; Zhang, H. Nat. Rev. Drug Discov. 2021, 20, 689. doi: 10.1038/s41573-021-00233-1
[31]	Wei, Y. -G. Polyoxometalates 2022, 1, 9140014. doi: 10.26599/POM.2022.9140014
[32]	Zhang, H.-Y.; Zhao, W.; Li, H.-Q.; Zhuang, Q.-H.; Sun, Z.-Q.; Cui, D.-Y.; Chen, X.-J.; Guo, A.; Ji, X.; An, S.; Chen, W.; Song, Y. Polyoxometalates 2022, 1, 9140011. doi: 10.26599/POM.2022.9140011
[33]	Feng, X.-J.; Li, Y.-G.; Zhang, Z.-M.; Wang, E.-B. Acta Chim. Sinica 2013, 71, 1575 (in Chinese). doi: 10.6023/A13060664
	(冯小佳, 李阳光, 张志明, 王恩波, 化学学报, 2013, 71, 1575.)
[34]	Wang, H.-N.; Zhang, A.-G.; Zhang, Z.-T.; Hong, R.; Yue, Q.; Zhao, X.; Lu, Y.; Liu, S.-X. Acta Chim. Sinica 2021, 79, 920 (in Chinese). doi: 10.6023/A21040130
	(王赫男, 张安歌, 张仲田, 洪瑞, 岳倩, 赵雪, 鹿颖, 刘术侠, 化学学报, 2021, 79, 920.)
[35]	Wei, Z.-Y.; Chang, Y.-L.; Yu, H.; Han, S.; Wei, Y.-G. Acta Chim. Sinica 2020, 78, 725 (in Chinese). doi: 10.6023/A20050187
	(魏哲宇, 常亚林, 余焓, 韩生, 魏永革, 化学学报, 2020, 78, 725.)
[36]	Liu, S.-X.; Wang, C.-L.; Yu, M.; Li, Y.-X.; Wang, E.-B. Acta Chim. Sinica 2005, 63, 1069 (in Chinese).
	(刘术侠, 王春玲, 于淼, 李玉新, 王恩波, 化学学报, 2005, 63, 1069.)
[37]	Chen, K.; Dai, G.-Y.; Liu, S.-Q.; Wei, Y.-G. Chin. Chem. Lett. 2023, 34, 107638. doi: 10.1016/j.cclet.2022.06.061
[38]	Li, B.; Wu, L.-X. Polyoxometalates 2023, 2, 9140016. doi: 10.26599/POM.2022.9140016
[39]	Li, J.; Zhang, D.; Chi, Y.; Hu, C. Polyoxometalates 2022, 1, 9140012. doi: 10.26599/POM.2022.9140012
[40]	Xia, Y.; Wei, Y.-G.; Guo, H.-Y. Acta Chim. Sinica 2005, 63, 1931 (in Chinese).
	(夏芸, 魏永革, 郭洪猷, 化学学报, 2005, 63, 1931.)
[41]	Du, D.-Y.; Yan, L.-K.; Su, Z.-M.; Li, S.-L.; Lan, Y.-Q.; Wang, E.-B. Coord. Chem. Rev. 2013, 257, 702. doi: 10.1016/j.ccr.2012.10.004
[42]	Chen, L.; Chen, W.-L.; Wang, X.-L.; Li, Y.-G.; Su, Z.-M.; Wang, E.-B. Chem. Soc. Rev. 2019, 48, 260. doi: 10.1039/C8CS00559A
[43]	Li, N.; Liu, J.; Dong, B.-X; Lan, Y.-Q. Angew. Chem. Int. Ed. 2020, 59, 20779. doi: 10.1002/anie.v59.47
[44]	Wang, Z.-M; Xin, X.; Zhang, M.; Li, Z.; Lv, H.-J; Yang, G.-Y. Sci. China-Chem. 2022, 65, 1515. doi: 10.1007/s11426-022-1276-4
[45]	Bijelic, A.; Aureliano, M.; Rompel, A. Angew. Chem. Int. Ed. 2019, 58, 2980. doi: 10.1002/anie.v58.10
[46]	Aureliano, M.; Gumerova, N. I.; Sciortino, G.; Garribba, E.; Rompel, A.; Crans, D. C. Coord. Chem. Rev. 2021, 447, 214143. doi: 10.1016/j.ccr.2021.214143
[47]	Francese, R.; Civra, A.; Ritta, M.; Donalisio, M.; Argenziano, M.; Cavalli, R.; Mougharbel, A. S.; Kortz, U.; Lembo, D. Antiviral Res. 2019, 163, 29. doi: 10.1016/j.antiviral.2019.01.005
[48]	Chen, X.-S.; Shuai, D.; Jiang, Z.-D.; Yang, H.; Luo, D.; Ni, H.; Wang, L.; Chen, B.-N. Acta Chim. Sinica 2022, 80, 116 (in Chinese). doi: 10.6023/A21110528
	(陈祥松, 帅蝶, 姜泽东, 杨晗, 罗丹, 倪辉, 王力, 陈丙年, 化学学报, 2022, 80, 116.)
[49]	Shuai, D.; Zhao, M.-J.; Chen, B.-N.; Wang, L. Chem. J. Chin. Univ. 2021, 42, 3579 (in Chinese).
	(帅蝶, 赵美娟, 陈丙年, 王力, 高等学校化学学报, 2021, 42, 3579.)
[50]	Lyon, D. K.; Miller, W. K.; Novet, T.; Domaille, P. J.; Evitt, E.; Johnson, D. C.; Finke, R. G. J. Am. Chem. Soc. 1991, 113, 7209. doi: 10.1021/ja00019a018
[51]	Qian, X.-Y.; Tong, X.; Wu, Q.-Y.; He, Z.-Q.; Cao, F.-H.; Yan, W.-F. Dalton Trans. 2012, 41, 9897. doi: 10.1039/c2dt30467h
[52]	Xu, Y.-P.; Yu, H.; Jiang, X.; Shi, J.-J.; Li, B.; Li, L.; Wu, L.-X.; Wang, M. Chin. J. Chem. 2022, 40, 813. doi: 10.1002/cjoc.v40.7
[53]	Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Free Radic. Biol. Med. 1999, 26, 1231. doi: 10.1016/S0891-5849(98)00315-3
[54]	Foh, M. B. K.; Amadou, I.; Foh, B. M.; Kamara, M. T.; Xia, W. Int. J. Mol. Sci. 2010, 11, 1851. doi: 10.3390/ijms11041851
[55]	Zhu, Y.; Qiu, L.; Zhou, J.; Guo, H.; Hu, Y.; Li, Z.; Wang, Q.; Chen, Q.; Liu, B. J. Enzym. Inhib. Med. Chem. 2010, 25, 798. doi: 10.3109/14756360903476398
[56]	Chen, X.-S.; Shuai, D.; Yang, H.; Luo, D.; Wang, L.; Chen, B.-N. Z. Anorg. Allg. Chem. 2022, 648, e202100319.
[57]	Thaipong, K.; Boonprakob, U.; Crosby, K.; Cisneros-Zevallos, L.; Byrne, D. H. J. Food Compos. Anal. 2006, 19, 669. doi: 10.1016/j.jfca.2006.01.003
[58]	Yu, X.; Yang, M.; Dong, J.; Shen, R. J. Food Sci. 2018, 83, 844. doi: 10.1111/jfds.2018.83.issue-3
[59]	Wang, L.-Y.; Ma, M.-T.; Yu, Z.-P.; Du, S.-K. Food Chem. 2021, 352, 129399. doi: 10.1016/j.foodchem.2021.129399
[60]	Huang, S.-Q.; Ding, S.-D.; Fan, L.-P. Int. J. Biol. Macromol. 2012, 50, 1183. doi: 10.1016/j.ijbiomac.2012.03.019

多酸型α-葡萄糖苷酶抑制剂的抗氧化性能研究