Discovery of novel flavonoid derivatives as potential dual inhibitors against α-glucosidase and α-amylase: virtual screening, synthesis, and biological evaluation.

Publisher: ESCOM Science Publishers Country of Publication: Netherlands NLM ID: 9516534 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-501X (Electronic) Linking ISSN: 13811991 NLM ISO Abbreviation: Mol Divers Subsets: MEDLINE

Original Publication: Leiden, The Netherlands : ESCOM Science Publishers, c1995-

Flavonoids*/chemistry ; Flavonoids*/pharmacology ; Glycoside Hydrolase Inhibitors*/chemistry ; Glycoside Hydrolase Inhibitors*/pharmacology ; Glycoside Hydrolase Inhibitors*/chemical synthesis ; Molecular Docking Simulation* ; alpha-Amylases*/antagonists & inhibitors ; alpha-Amylases*/chemistry ; alpha-Glucosidases*/metabolism ; alpha-Glucosidases*/chemistry ; Molecular Dynamics Simulation*; Structure-Activity Relationship ; Drug Discovery ; Drug Evaluation, Preclinical ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/chemical synthesis

Diabetes mellitus is one of the top ten causes of death worldwide, accounting for 6.7 million deaths in 2021, and is one of the most rapidly growing global health emergencies of this century. Although several classes of therapeutic drugs have been invented and applied in clinical practice, diabetes continues to pose a serious and growing threat to public health and places a tremendous burden on those affected and their families. The strategy of reducing carbohydrate digestibility by inhibiting the activities of α-glucosidase and α-amylase is regarded as a promising preventative treatment for type 2 diabetes. In this study, we investigated the dual inhibitory effect against two polysaccharide hydrolytic enzymes of flavonoid derivatives from an in-house chemical database. By combining molecular docking and structure-activity relationship analysis, twelve compounds with docking energies less than or equal to - 8.0 kcal mol ^-1 and containing required structural features for dual inhibition of the two enzymes were identified and subjected to chemical synthesis and in vitro evaluation. The obtained results showed that five compounds exhibited dual inhibitory effects on the target enzymes with better IC 50 values than the approved positive control acarbose. Molecular dynamics simulations were performed to elucidate the binding of these flavonoids to the enzymes. The predicted pharmacokinetic and toxicological properties suggest that these compounds are viable for further development as type 2 diabetes drugs.
(© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Sapra A, Vaqar S, Bhandari P (2019) Diabetes Mellitus. In: StatPearls [Internet] (ed). StatPearls Publishing, Treasure Island (FL), pp 1–12.
IDF Diabetes Atlas. Available at https://www.diabetesatlas.org . Accessed 30 Dec 2022.
Deshpande AD, Harris-Hayes M, Schootman M (2008) Epidemiology of Diabetes and diabetes-related complications. Phys Ther 88:1254–1264. https://doi.org/10.2522/ptj.20080020. (PMID: 10.2522/ptj.20080020188018583870323)
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, and on behalf of the American Diabetes A (2022) Classification and diagnosis of diabetes: standards of care in diabetes—2023. Diabetes Care 46:S19–S40. https://doi.org/10.2337/dc23-S002. (PMID: 10.2337/dc23-S0029810477)
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, Association obotAD, (2022) 9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes—2023. Diabetes Care 46:S140–S157. https://doi.org/10.2337/dc23-S009. (PMID: 10.2337/dc23-S0099810476)
Ghani U (2020) Chapter one - Introduction, rationale and the current clinical status of oral α-glucosidase inhibitors. In: Ghani U (ed) Alpha-glucosidase inhibitors. Elsevier, Amsterdam, pp 1–15.
Gong L, Feng D, Wang T, Ren Y, Liu Y, Wang J (2020) Inhibitors of α-amylase and α-glucosidase: potential linkage for whole cereal foods on prevention of hyperglycemia. Food Sci Nutr 8:6320–6337. https://doi.org/10.1002/fsn3.1987. (PMID: 10.1002/fsn3.1987333125197723208)
Poovitha S, Parani M (2016) In vitro and in vivo α-amylase and α-glucosidase inhibiting activities of the protein extracts from two varieties of bitter gourd (Momordica charantia L.). BMC Complement Altern Med 16:185. https://doi.org/10.1186/s12906-016-1085-1. (PMID: 10.1186/s12906-016-1085-1274544184959359)
Chiasson J-L, Josse RG, Leiter LA, Mihic M, Nathan DM, Palmason C, Cohen RM, Wolever TM (1996) The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance. Diabetes Care 19:1190–1193. https://doi.org/10.2337/diacare.19.11.1190. (PMID: 10.2337/diacare.19.11.11908908378)
Brayer GD, Luo Y, Withers SG (1995) The structure of human pancreatic α-amylase at 1.8 Å resolution and comparisons with related enzymes. Protein Sci 4:1730–1742. https://doi.org/10.1002/pro.5560040908. (PMID: 10.1002/pro.556004090885280712143216)
Proença C, Ribeiro D, Freitas M, Fernandes E (2022) Flavonoids as potential agents in the management of type 2 diabetes through the modulation of α-amylase and α-glucosidase activity: a review. Crit Rev Food Sci Nutr 62:3137–3207. https://doi.org/10.1080/10408398.2020.1862755. (PMID: 10.1080/10408398.2020.186275533427491)
Li C, Begum A, Numao S, Park KH, Withers SG, Brayer GD (2005) Acarbose rearrangement mechanism implied by the kinetic and structural analysis of human pancreatic α-amylase in complex with analogues and their elongated counterparts. Biochemistry 44:3347–3357. https://doi.org/10.1021/bi048334e. (PMID: 10.1021/bi048334e15736945)
Sim L, Willemsma C, Mohan S, Naim HY, Pinto BM, Rose DR (2010) Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains. J Biol Chem 285:17763–17770. https://doi.org/10.1074/jbc.M109.078980. (PMID: 10.1074/jbc.M109.078980203568442878540)
Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, Rose DR (2008) Human intestinal maltase–glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. J Mol Biol 375:782–792. https://doi.org/10.1016/j.jmb.2007.10.069. (PMID: 10.1016/j.jmb.2007.10.06918036614)
Ren L, Qin X, Cao X, Wang L, Bai F, Bai G, Shen Y (2011) Structural insight into substrate specificity of human intestinal maltase-glucoamylase. Protein Cell 2:827–836. https://doi.org/10.1007/s13238-011-1105-3. (PMID: 10.1007/s13238-011-1105-3220580374875297)
Le M-T, Trinh D-TT, Ngo T-D, Tran-Nguyen V-K, Nguyen D-N, Hoang T, Nguyen H-M, Do T-G-S, Mai TT, Tran T-D, Thai K-M (2022) Chalcone derivatives as potential inhibitors of P-glycoprotein and NorA: an in silico and in vitro study. BioMed Res Int 2022:9982453. https://doi.org/10.1155/2022/9982453. (PMID: 10.1155/2022/9982453353787888976639)
Ashraf J, Mughal EU, Sadiq A, Naeem N, Muhammad SA, Qousain T, Zafar MN, Khan BA, Anees M (2020) Design and synthesis of new flavonols as dual ɑ-amylase and ɑ-glucosidase inhibitors: structure-activity relationship, drug-likeness, in vitro and in silico studies. J Mol Struct 1218:128458. https://doi.org/10.1016/j.molstruc.2020.128458. (PMID: 10.1016/j.molstruc.2020.128458)
Ullah A, Munir S, Badshah SL, Khan N, Ghani L, Poulson BG, Emwas A-H, Jaremko M (2020) Important flavonoids and their role as a therapeutic agent. Molecules 25:5243. https://doi.org/10.3390/molecules25225243. (PMID: 10.3390/molecules252252437697716)
Zhu J, Chen C, Zhang B, Huang Q (2020) The inhibitory effects of flavonoids on α-amylase and α-glucosidase. Crit Rev Food Sci Nutr 60:695–708. https://doi.org/10.1080/10408398.2018.1548428. (PMID: 10.1080/10408398.2018.1548428)
Mahapatra DK, Asati V, Bharti SK (2015) Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives. Eur J Med Chem 92:839–865. https://doi.org/10.1016/j.ejmech.2015.01.051. (PMID: 10.1016/j.ejmech.2015.01.05125638569)
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242. https://doi.org/10.1093/nar/28.1.235. (PMID: 10.1093/nar/28.1.23510592235102472)
Khoo CM (2017) Diabetes Mellitus treatment. In: Quah SR (ed) International encyclopedia of public health, 2nd edn. Academic Press, Oxford, pp 288–293. (PMID: 10.1016/B978-0-12-803678-5.00108-9)
Williams LK, Li C, Withers SG, Brayer GD (2012) Order and disorder: differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target. J Med Chem 55:10177–10186. https://doi.org/10.1021/jm301273u. (PMID: 10.1021/jm301273u23050660)
Lasko TA, Bhagwat JG, Zou KH, Ohno-Machado L (2005) The use of receiver operating characteristic curves in biomedical informatics. J Biomed Inform 38:404–415. https://doi.org/10.1016/j.jbi.2005.02.008. (PMID: 10.1016/j.jbi.2005.02.00816198999)
Erickson JA, Jalaie M, Robertson DH, Lewis RA, Vieth M (2004) Lessons in molecular recognition: the effects of ligand and protein flexibility on molecular docking accuracy. J Med Chem 47:45–55. https://doi.org/10.1021/jm030209y. (PMID: 10.1021/jm030209y14695819)
Mysinger MM, Carchia M, Irwin JJ, Shoichet BK (2012) Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking. J Med Chem 55:6582–6594. https://doi.org/10.1021/jm300687e. (PMID: 10.1021/jm300687e227160433405771)
Empereur-Mot C, Zagury J-F, Montes M (2016) Screening explorer–an interactive tool for the analysis of screening results. J Chem Inf Model 56:2281–2286. https://doi.org/10.1021/acs.jcim.6b00283. (PMID: 10.1021/acs.jcim.6b0028327808512)
Empereur-mot C, Guillemain H, Latouche A, Zagury J-F, Viallon V, Montes M (2015) Predictiveness curves in virtual screening. J Cheminform 7:52. https://doi.org/10.1186/s13321-015-0100-8. (PMID: 10.1186/s13321-015-0100-8265392504631717)
Molecular Operating Environment (MOE) (2022) Version 2022.10. Chemical Computing Group Inc., Montreal.
O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) Open babel: an open chemical toolbox. J Cheminform 3:33. https://doi.org/10.1186/1758-2946-3-33. (PMID: 10.1186/1758-2946-3-33219823003198950)
Eberhardt J, Santos-Martins D, Tillack AF, Forli S (2021) AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings. J Chem Inf Model 61:3891–3898. https://doi.org/10.1021/acs.jcim.1c00203. (PMID: 10.1021/acs.jcim.1c002033427879410683950)
Adasme MF, Linnemann KL, Bolz SN, Kaiser F, Salentin S, Haupt VJ, Schroeder M (2021) PLIP 2021: expanding the scope of the protein–ligand interaction profiler to DNA and RNA. Nucleic Acids Res 49:W530–W534. https://doi.org/10.1093/nar/gkab294. (PMID: 10.1093/nar/gkab294339502148262720)
Liu M, Yin H, Liu G, Dong J, Qian Z, Miao J (2014) Xanthohumol, a prenylated chalcone from beer hops, acts as an α-glucosidase inhibitor in vitro. J Agric Food Chem 62:5548–5554. https://doi.org/10.1021/jf500426z. (PMID: 10.1021/jf500426z24897556)
Proença C, Freitas M, Ribeiro D, Oliveira EFT, Sousa JLC, Tomé SM, Ramos MJ, Silva AMS, Fernandes PA, Fernandes E (2017) α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure–activity relationship study. J Enzyme Inhib Med Chem 32:1216–1228. https://doi.org/10.1080/14756366.2017.1368503. (PMID: 10.1080/14756366.2017.1368503289335646009965)
Sun H, Song X, Tao Y, Li M, Yang K, Zheng H, Jin Z, Dodd RH, Pan G, Lu K, Yu P (2018) Synthesis & α-glucosidase inhibitory & glucose consumption-promoting activities of flavonoid–coumarin hybrids. Future Med Chem 10:1055–1066. https://doi.org/10.4155/fmc-2017-0293. (PMID: 10.4155/fmc-2017-029329676183)
Seo WD, Kim JH, Kang JE, Ryu HW, Curtis-Long MJ, Lee HS, Yang MS, Park KH (2005) Sulfonamide chalcone as a new class of α-glucosidase inhibitors. Bioorg Med Chem Lett 15:5514–5516. https://doi.org/10.1016/j.bmcl.2005.08.087. (PMID: 10.1016/j.bmcl.2005.08.08716202584)
Chatsumpun N, Sritularak B, Likhitwitayawuid K (2017) New biflavonoids with α-glucosidase and pancreatic lipase inhibitory activities from boesenbergia rotunda. Molecules 22:1862. https://doi.org/10.3390/molecules22111862. (PMID: 10.3390/molecules22111862290841646150212)
Cheng N, Yi W-B, Wang Q-Q, Peng S-M, Zou X-Q (2014) Synthesis and α-glucosidase inhibitory activity of chrysin, diosmetin, apigenin, and luteolin derivatives. Chin Chem Lett 25:1094–1098. https://doi.org/10.1016/j.cclet.2014.05.021. (PMID: 10.1016/j.cclet.2014.05.021)
Chen Y-G, Li P, Li P, Yan R, Zhang X-Q, Wang Y, Zhang X-T, Ye W-C, Zhang Q-W (2013) α-Glucosidase inhibitory effect and simultaneous quantification of three major flavonoid glycosides in microctis folium. Molecules 18:4221–4232. https://doi.org/10.3390/molecules18044221. (PMID: 10.3390/molecules18044221236124746270556)
Tajudeen Bale A, Mohammed Khan K, Salar U, Chigurupati S, Fasina T, Ali F, Kanwal WA, Taha M, Sekhar Nanda S, Ghufran M, Perveen S (2018) Chalcones and bis-chalcones: as potential α-amylase inhibitors; synthesis, in vitro screening, and molecular modelling studies. Bioorg Chem 79:179–189. https://doi.org/10.1016/j.bioorg.2018.05.003. (PMID: 10.1016/j.bioorg.2018.05.00329763804)
Saleem F, Kanwal KKM, Chigurupati S, Solangi M, Nemala AR, Mushtaq M, Ul-Haq Z, Taha M, Perveen S (2021) Synthesis of azachalcones, their α-amylase, α-glucosidase inhibitory activities, kinetics, and molecular docking studies. Bioorg Chem 106:104489. https://doi.org/10.1016/j.bioorg.2020.104489. (PMID: 10.1016/j.bioorg.2020.10448933272713)
Sahnoun M, Trabelsi S, Bejar S (2017) Citrus flavonoids collectively dominate the α-amylase and α-glucosidase inhibitions. Biologia 72:764–773. https://doi.org/10.1515/biolog-2017-0091. (PMID: 10.1515/biolog-2017-0091)
Li K, Yao F, Xue Q, Fan H, Yang L, Li X, Sun L, Liu Y (2018) Inhibitory effects against α-glucosidase and α-amylase of the flavonoids-rich extract from Scutellaria baicalensis shoots and interpretation of structure–activity relationship of its eight flavonoids by a refined assign-score method. Chem Cent J 12:82. https://doi.org/10.1186/s13065-018-0445-y. (PMID: 10.1186/s13065-018-0445-y6042199)
Meshram G, Vala V, Wagh P, Deshpande SS (2016) Ultrasound accelerated synthesis of novel benzimidazole derived chalcones as glucosidases inhibitor and antimicrobial agents. Indian J Chem Sect B 55:613–623.
Kiruthiga N, Prabha T, Selvinthanuja C, Srinivasan K, Sivakumar T (2018) Design, synthesis and evaluation of recent flavones as anti-diabetics. Int J Chem Pharm Anal 5:1–12.
Lo Piparo E, Scheib H, Frei N, Williamson G, Grigorov M, Chou CJ (2008) Flavonoids for Controlling starch digestion: structural requirements for inhibiting human α-amylase. J Med Chem 51:3555–3561. https://doi.org/10.1021/jm800115x. (PMID: 10.1021/jm800115x18507367)
Tran T-D, Nguyen T-C-V, Nguyen N-S, Nguyen D-M, Nguyen T-T-H, Le M-T, Thai K-M (2016) Synthesis of novel chalcones as acetylcholinesterase inhibitors. Appl Sci 6:198. https://doi.org/10.3390/app6070198. (PMID: 10.3390/app6070198)
Wang Z-W, Wang J-S, Luo J, Kong L-Y (2013) α-Glucosidase inhibitory triterpenoids from the stem barks of Uncaria laevigata. Fitoterapia 90:30–37. https://doi.org/10.1016/j.fitote.2013.07.005. (PMID: 10.1016/j.fitote.2013.07.00523856092)
Granados-Guzmán G, Castro-Ríos R, Waksman de Torres N, Salazar-Aranda R (2018) Optimization and validation of a microscale in vitro method to assess α-glucosidase inhibition activity. Curr Anal Chem 14:458–464. (PMID: 10.2174/1573411013666170911154755302942496142409)
Kusano R, Ogawa S, Matsuo Y, Tanaka T, Yazaki Y, Kouno I (2011) α-Amylase and lipase inhibitory activity and structural characterization of acacia bark proanthocyanidins. J Nat Prod 74:119–128. https://doi.org/10.1021/np100372t. (PMID: 10.1021/np100372t21192716)
Xiao Z, Storms R, Tsang A (2006) A quantitative starch-iodine method for measuring alpha-amylase and glucoamylase activities. Anal Biochem 351:146–148. https://doi.org/10.1016/j.ab.2006.01.036. (PMID: 10.1016/j.ab.2006.01.03616500607)
Ahmed MU, Ibrahim A, Dahiru NJ, Mohammed HS (2020) Alpha amylase inhibitory potential and mode of inhibition of oils from Allium sativum (Garlic) and Allium cepa (Onion). Clin Med Insights Endocrinol Diabetes 13:1179551420963106. https://doi.org/10.1177/1179551420963106. (PMID: 10.1177/1179551420963106330881877545766)
Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, Lindahl E (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2:19–25. https://doi.org/10.1016/j.softx.2015.06.001. (PMID: 10.1016/j.softx.2015.06.001)
Mackerell AD Jr, Feig M, Brooks Iii CL (2004) Extending the treatment of backbone energetics in protein force fields: Limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J Comput Chem 25:1400–1415. https://doi.org/10.1002/jcc.20065. (PMID: 10.1002/jcc.2006515185334)
Zoete V, Cuendet MA, Grosdidier A, Michielin O (2011) SwissParam: A fast force field generation tool for small organic molecules. J Comput Chem 32:2359–2368. https://doi.org/10.1002/jcc.21816. (PMID: 10.1002/jcc.2181621541964)
Bhardwaj VK, Singh R, Sharma J, Rajendran V, Purohit R, Kumar S (2021) Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors. J Biomol Struct Dyn 39:3449–3458. https://doi.org/10.1080/07391102.2020.1766572. (PMID: 10.1080/07391102.2020.176657232397940)
Humphrey W, Dalke A, Schulten K (1996) VMD: Visual molecular dynamics. J Mol Graph 14:33–38. https://doi.org/10.1016/0263-7855(96)00018-5. (PMID: 10.1016/0263-7855(96)00018-58744570)
Schrödinger LLC., The PyMOL Molecular Graphics System. 2020. 2.0.
Guerra F, Siemers M, Mielack C, Bondar A-N (2018) Dynamics of long-distance hydrogen-bond networks in photosystem II. J Phys Chem B 122:4625–4641. https://doi.org/10.1021/acs.jpcb.8b00649. (PMID: 10.1021/acs.jpcb.8b0064929589763)
Dong J, Wang N-N, Yao Z-J, Zhang L, Cheng Y, Ouyang D, Lu A-P, Cao D-S (2018) ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively collected ADMET database. J Cheminform 10:29. https://doi.org/10.1186/s13321-018-0283-x. (PMID: 10.1186/s13321-018-0283-x299430746020094)
Yadav P, Lal K, Kumar A, Guru SK, Jaglan S, Bhushan S (2017) Green synthesis and anticancer potential of chalcone linked-1,2,3-triazoles. Eur J Med Chem 126:944–953. https://doi.org/10.1016/j.ejmech.2016.11.030. (PMID: 10.1016/j.ejmech.2016.11.03028011424)
Nasli Esfahani A, Iraji A, Alamir A, Moradi S, Asgari MS, Hosseini S, Mojtabavi S, Nasli-Esfahani E, Faramarzi MA, Bandarian F, Larijani B, Hamedifar H, Hajimiri MH, Mahdavi M (2022) Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors. Mol Divers 26:1995–2009. https://doi.org/10.1007/s11030-021-10310-7. (PMID: 10.1007/s11030-021-10310-734515954)
Zawawi NKNA, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F (2017) Synthesis, molecular docking studies of hybrid benzimidazole as α-glucosidase inhibitor. Bioorg Chem 70:184–191. https://doi.org/10.1016/j.bioorg.2016.12.009. (PMID: 10.1016/j.bioorg.2016.12.00928043716)
Halliwell B, Rafter J, Jenner A (2005) Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not? Am J Clin Nutr 81:268S-276S. https://doi.org/10.1093/ajcn/81.1.268S. (PMID: 10.1093/ajcn/81.1.268S15640490)
Fan X, Fan Z, Yang Z, Huang T, Tong Y, Yang D, Mao X, Yang M (2022) Flavonoids-natural gifts to promote health and longevity. Int J Mol Sci 23:2176. https://doi.org/10.3390/ijms23042176. (PMID: 10.3390/ijms23042176352162908879655)
Xu SL, Zhu KY, Bi CW, Yan L, Men SW, Dong TT, Tsim KW (2013) Flavonoids, derived from traditional Chinese medicines, show roles in the differentiation of neurons: possible targets in developing health food products. Birth Defects Res C Embryo Today 99:292–299. https://doi.org/10.1002/bdrc.21054. (PMID: 10.1002/bdrc.2105424339039)
Lam TP, Tran NVN, Pham LHD, Lai NVT, Dang BTN, Truong NLN, Nguyen-Vo SK, Mai TT, Tran TD (2023) Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies. J Chem. https://doi.org/10.26434/chemrxiv-2023-cdlf8-v3.
Ryu HW, Lee BW, Curtis-Long MJ, Jung S, Ryu YB, Lee WS, Park KH (2010) Polyphenols from broussonetia papyrifera displaying potent α-glucosidase inhibition. J Agric Food Chem 58:202–208. https://doi.org/10.1021/jf903068k. (PMID: 10.1021/jf903068k19954213)
Rocha S, Sousa A, Ribeiro D, Correia CM, Silva VLM, Santos CMM, Silva AMS, Araújo AN, Fernandes E, Freitas M (2019) A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives. Food Funct 10:5510–5520. https://doi.org/10.1039/C9FO01298B. (PMID: 10.1039/C9FO01298B31414099)
Basu S, Debroy R, Kumar H, Singh H, Ramaiah S, Anbarasu A (2023) Bioactive phytocompounds against specific target proteins of Borrelia recurrentis responsible for louse-borne relapsing fever: genomics and structural bioinformatics evidence. Med Vet Entomol 37:213–218. https://doi.org/10.1111/mve.12623. (PMID: 10.1111/mve.1262336377635)

162/2019/HĐ-ĐHYD University of Medicine and Pharmacy at Ho Chi Minh City

Keywords: Biological evaluation; Chalcone; Diabetes treatment; Dual actions; Dynamics simulations; Molecular docking

0 (Flavonoids)
0 (Glycoside Hydrolase Inhibitors)
EC 3.2.1.1 (alpha-Amylases)
EC 3.2.1.20 (alpha-Glucosidases)
0 (Enzyme Inhibitors)

Date Created: 20230627 Date Completed: 20240724 Latest Revision: 20240724

20240726

10.1007/s11030-023-10680-0

37369956