Assessment of Anticholinergic and Antidiabetic Properties of Some Natural and Synthetic Molecules: An In vitro and In silico Approach


Cite item

Full Text

Abstract

Introduction:This study aimed to determine the in vitro and in silico effects of some natural and synthetic molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes.

Background:Alzheimer's disease (AD) and Type II diabetes mellitus (T2DM) are considered the most important diseases of today’s world. However, the side effects of therapeutic agents used in both diseases limit their use. Therefore, developing drugs with high therapeutic efficacy and better pharmacological profile is important.

Objective:This study sets out to determine the related enzyme inhibitors used in treating AD and T2DM, considered amongst the most important diseases of today’s world.

Methods:In the current study, the in vitro and in silico effects of dienestrol, hesperetin, Lthyroxine, 3,3',5-Triiodo-L-thyronine (T3) and dobutamine molecules on AChE, BChE and α- glycosidase enzyme activities were investigated.

Results:All the molecules showed an inhibitory effect on the enzymes. The IC50 and Ki values of the L-Thyroxine molecule, which showed the strongest inhibition effect for the AChE enzyme, were determined as 1.71 µM and 0.83 ± 0.195 µM, respectively. In addition, dienestrol, T3, and dobutamine molecules showed a more substantial inhibition effect than tacrine. The dobutamine molecule showed the most substantial inhibition effect for the BChE enzyme, and IC50 and Ki values were determined as 1.83 µM and 0.845 ± 0.143 µM, respectively. The IC50 and Ki values for the hesperetin molecule, which showed the strongest inhibition for the α-glycosidase enzyme, were determined as 13.57 µM and 12.33 ± 2.57 µM, respectively.

Conclusion:According to the results obtained, the molecules used in the study may be considered potential inhibitor candidates for AChE, BChE and α-glycosidase.

About the authors

Veysel Çomaklı

Department of Nutrition and Dietetics, İbrahim Çeçen University of Ağrı

Author for correspondence.
Email: info@benthamscience.net

İmdat Aygül

Department of Nutrition and Dietetics,, Gümüşhane University

Email: info@benthamscience.net

Rüya Sağlamtaş

Department of Medical Services and Techniques,, İbrahim Çeçen University of Ağrı,

Email: info@benthamscience.net

Müslüm Kuzu

Department of NutritioDepartment of Nutrition and Dieteticsn and Dietetics, Karabük University

Email: info@benthamscience.net

Ramazan Demirdağ

Department of Nutrition and Dietetics, İbrahim Çeçen University of Ağrı

Email: info@benthamscience.net

Hülya Akincioğlu

Department of Chemistry, İbrahim Çeçen University of Ağrı

Email: info@benthamscience.net

Şevki Adem

Department of Chemistry, Çankırı Karatekin University

Email: info@benthamscience.net

İlhami Gülçin

Department of Chemistry, Atatürk University

Email: info@benthamscience.net

References

  1. Friedli, M.J.; Inestrosa, N.C. Huperzine A and its neuroprotective molecular signaling in alzheimer’s disease. Molecules, 2021, 26(21), 6531. doi: 10.3390/molecules26216531 PMID: 34770940
  2. Chiang, T.I.; Yu, Y.H.; Lin, C.H.; Lane, H.Y. Novel biomarkers of alzheimer’s disease: Based upon N-methyl-D-aspartate receptor hypoactivation and oxidative stress. Clin. Psychopharmacol. Neurosci., 2021, 19(3), 423-433. doi: 10.9758/cpn.2021.19.3.423 PMID: 34294612
  3. Aras, A.; Türkan, F.; Yildiko, U.; Atalar, M.N.; Kılıç, Ö.; Alma, M.H.; Bursal, E. Biochemical constituent, enzyme inhibitory activity, and molecular docking analysis of an endemic plant species, Thymus migricus. Chem. Pap., 2021, 75(3), 1133-1146. doi: 10.1007/s11696-020-01375-z
  4. Bartolini, M.; Bertucci, C.; Cavrini, V.; Andrisano, V. β-Amyloid aggregation induced by human acetylcholinesterase: Inhibition studies. Biochem. Pharmacol., 2003, 65(3), 407-416. doi: 10.1016/S0006-2952(02)01514-9 PMID: 12527333
  5. Lolak, N.; Akocak, S.; Türkeş, C.; Taslimi, P.; Işık, M.; Beydemir, Ş.; Gülçin, İ.; Durgun, M. Synthesis, characterization, inhibition effects, and molecular docking studies as acetylcholinesterase, α-glycosidase, and carbonic anhydrase inhibitors of novel benzenesulfonamides incorporating 1,3,5-triazine structural motifs. Bioorg. Chem., 2020, 100, 103897. doi: 10.1016/j.bioorg.2020.103897 PMID: 32413628
  6. Türkan, F.; Huyut, Z.; Taslimi, P.; Gülçin, İ. The effects of some antibiotics from cephalosporin groups on the acetylcholinesterase and butyrylcholinesterase enzymes activities in different tissues of rats. Arch. Physiol. Biochem., 2019, 125(1), 12-18. doi: 10.1080/13813455.2018.1427766 PMID: 29364753
  7. Benazzouz-Touami, A.; Chouh, A.; Halit, S.; Terrachet-Bouaziz, S.; Makhloufi-Chebli, M.; Ighil-Ahriz, K.; Silva, A.M.S. New Coumarin-Pyrazole hybrids: Synthesis, Docking studies and Biological evaluation as potential cholinesterase inhibitors. J. Mol. Struct., 2022, 1249, 131591. doi: 10.1016/j.molstruc.2021.131591
  8. Domínguez, R.O.; Pagano, M.A.; Marschoff, E.R.; González, S.E.; Repetto, M.G.; Serra, J.A. Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: Associations and a hypothesis. Neurología, 2014, 29(9), 567-572. doi: 10.1016/j.nrleng.2014.10.001 PMID: 24140159
  9. Günsel, A.; Taslimi, P.; Atmaca, G.Y.; Bilgiçli, A.T.; Pişkin, H.; Ceylan, Y.; Erdoğmuş, A.; Yarasir, M.N.; Gülçin, İ. Novel potential metabolic enzymes inhibitor, photosensitizer and antibacterial agents based on water-soluble phthalocyanine bearing imidazole derivative. J. Mol. Struct., 2021, 1237, 130402. doi: 10.1016/j.molstruc.2021.130402
  10. Deswal, L.; Verma, V.; Devinder, K.; Deswal, Y.; Kumar, A.; Rajnish, K.; Parshad, M.; Bhatia, M. Synthesis, antimicrobial and α-Glucosidase inhibition of new benzimidazole-1,2,3-Triazole-Indoline derivatives: A combined experimental and computational venture. Chem. Pap., 2022, 1, 1-16.
  11. Gülçin, İ.; Trofimov, B.; Kaya, R.; Taslimi, P.; Sobenina, L.; Schmidt, E.; Petrova, O.; Malysheva, S.; Gusarova, N.; Farzaliyev, V.; Sujayev, A.; Alwasel, S.; Supuran, C.T. Synthesis of nitrogen, phosphorus, selenium and sulfur-containing heterocyclic compounds – Determination of their carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase and α-glycosidase inhibition properties. Bioorg. Chem., 2020, 103, 104171. doi: 10.1016/j.bioorg.2020.104171 PMID: 32891857
  12. Gülçin, İ.; Gören, A.C.; Taslimi, P.; Alwasel, S.H.; Kılıc, O.; Bursal, E. Anticholinergic, antidiabetic and antioxidant activities of Anatolian pennyroyal (Mentha pulegium)-analysis of its polyphenol contents by LC-MS/MS. Biocatal. Agric. Biotechnol., 2020, 23, 101441. doi: 10.1016/j.bcab.2019.101441
  13. Tam, K.Y.; Ju, Y. Pathological mechanisms and therapeutic strategies for Alzheimer’s disease. Neural Regen. Res., 2022, 17(3), 543-549. doi: 10.4103/1673-5374.320970 PMID: 34380884
  14. Akocak, S.; Taslimi, P.; Lolak, N.; Işık, M.; Durgun, M.; Budak, Y.; Türkeş, C.; Gülçin, İ.; Beydemir, Ş. Synthesis, characterization, and inhibition study of novel substituted phenylureido sulfaguanidine derivatives as α‐Glycosidase and cholinesterase inhibitors. Chem. Biodivers., 2021, 18(4), e2000958. doi: 10.1002/cbdv.202000958 PMID: 33620128
  15. Wierzbicka, A.; Mańkowska‐wierzbicka, D.; Cieślewicz, S.; Stelmach‐mardas, M.; Mardas, M. Interventions preventing vaginitis, vaginal atrophy after brachytherapy or radiotherapy due to malignant tumors of the female reproductive organs-a systematic review. Int J Environ Res Public Health., 2021, 18(8), 3932.
  16. Carraher, C.E., Jr; Roner, M.R.; Shahi, K.; Barot, G. Structural Consideration in designing organotin polyethers to arrest the growth of breast cancer cells In vitro. Materials, 2011, 4(4), 801-815. doi: 10.3390/ma4040801 PMID: 28879951
  17. Hong, X.; Luo, X.; Wang, L.; Gong, D.; Zhang, G. New insights into the inhibition of hesperetin on polyphenol oxidase: Inhibitory kinetics, binding characteristics, conformational change and computational simulation. Foods, 2023, 12(4), 905. doi: 10.3390/foods12040905 PMID: 36832979
  18. Finan, B.; Parlee, S.D.; Yang, B. Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH. Mol. Metab., 2021, 46, 101153. doi: 10.1016/j.molmet.2020.101153 PMID: 33359400
  19. Mullur, R.; Liu, Y.Y.; Brent, G.A. Thyroid hormone regulation of metabolism. Physiol. Rev., 2014, 94(2), 355-382. doi: 10.1152/physrev.00030.2013 PMID: 24692351
  20. Ruffolo, R.R., Jr. The pharmacology of dobutamine. Am. J. Med. Sci., 1987, 294(4), 244-248. doi: 10.1097/00000441-198710000-00005 PMID: 3310640
  21. Ellman, G.L.; Courtney, K.D.; Andres, V., Jr.; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7(2), 88-95. doi: 10.1016/0006-2952(61)90145-9 PMID: 13726518
  22. Yiğit, M.; Celepci, D.B.; Taslimi, P.; Yiğit, B.; Çetinkaya, E.; Özdemir, İ.; Aygün, M.; Gülçin, İ. Selenourea and thiourea derivatives of chiral and achiral enetetramines: Synthesis, characterization and enzyme inhibitory properties. Bioorg. Chem., 2022, 120, 105566. doi: 10.1016/j.bioorg.2021.105566 PMID: 34974209
  23. Sujayev, A.; Taslimi, P.; Kaya, R.; Safarov, B.; Aliyeva, L.; Farzaliyev, V.; Gulçin, İ. Synthesis, characterization and biological evaluation of N ‐substituted triazinane‐2‐thiones and theoretical–experimental mechanism of condensation reaction. Appl. Organomet. Chem., 2020, 34(2), e5329. doi: 10.1002/aoc.5329
  24. Zengin, M.; Genc, H.; Taslimi, P.; Kestane, A.; Guclu, E.; Ogutlu, A.; Karabay, O.; Gulçin, İ. Novel thymol bearing oxypropanolamine derivatives as potent some metabolic enzyme inhibitors – Their antidiabetic, anticholinergic and antibacterial potentials. Bioorg. Chem., 2018, 81, 119-126. doi: 10.1016/j.bioorg.2018.08.003 PMID: 30118983
  25. Yılmaz, M.A.; Taslimi, P.; Kılıç, Ö.; Gülçin, İ.; Dey, A.; Bursal, E. Unravelling the phenolic compound reserves, antioxidant and enzyme inhibitory activities of an endemic plant species, Achillea pseudoaleppica. J. Biomol. Struct. Dyn., 2023, 41(2), 445-456. doi: 10.1080/07391102.2021.2007792 PMID: 34822320
  26. Akıncıoğlu, A.; Göksu, S.; Naderi, A.; Akıncıoğlu, H.; Kılınç, N.; Gülçin, İ. Cholinesterases, carbonic anhydrase inhibitory properties and in silico studies of novel substituted benzylamines derived from dihydrochalcones. Comput. Biol. Chem., 2021, 94, 107565. doi: 10.1016/j.compbiolchem.2021.107565 PMID: 34474201
  27. Tao, Y.; Zhang, Y.; Cheng, Y.; Wang, Y. Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomed. Chromatogr., 2013, 27(2), 148-155. doi: 10.1002/bmc.2761 PMID: 22674728
  28. Burmaoglu, S.; Yilmaz, A.O.; Taslimi, P.; Algul, O.; Kilic, D.; Gulcin, I. Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity. Arch. Pharm., 2018, 351(2), 1700314. doi: 10.1002/ardp.201700314 PMID: 29323749
  29. Taslimi, P.; Kandemir, F.M.; Demir, Y.; İleritürk, M.; Temel, Y.; Caglayan, C.; Gulçin, İ. The antidiabetic and anticholinergic effects of chrysin on cyclophosphamide‐induced multiple organ toxicity in rats: Pharmacological evaluation of some metabolic enzyme activities. J. Biochem. Mol. Toxicol., 2019, 33(6), e22313. doi: 10.1002/jbt.22313 PMID: 30801880
  30. Kuzu, M.; Aslan, A.; Ahmed, I.; Comakli, V.; Demirdag, R.; Uzun, N. Purification of glucose-6-phosphate dehydrogenase and glutathione reductase enzymes from the gill tissue of Lake Van fish and analyzing the effects of some chalcone derivatives on enzyme activities. Fish Physiol. Biochem., 2016, 42(2), 483-491. doi: 10.1007/s10695-015-0153-7 PMID: 26676512
  31. Türkoğlu, E.A.; Kuzu, M.; Ayasan, T.; Inci, H.; Eratak, S.V. Inhibitory effects of some flavonoids on thioredoxin reductase purified from chicken liver. Braz. J. Poult. Sci., 2019, 21(2), eRBCA-2019-0982. doi: 10.1590/1806-9061-2018-0982
  32. Temel, Y.; Koçyigit, U.M.; Taysı, M.Ş.; Gökalp, F.; Gürdere, M.B.; Budak, Y.; Ceylan, M.; Gülçin, İ.; Çiftci, M. Purification of glutathione S-transferase enzyme from quail liver tissue and inhibition effects of (3a R, 4 S, 7 R, 7a S)-2-(4-((E)-3-(aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1 H -4,7-methanoisoindole-1,3(2 H)-dione derivatives on the enzyme activity. J. Biochem. Mol. Toxicol., 2018, 32(3), e22034. doi: 10.1002/jbt.22034 PMID: 29350485
  33. Metzler, M.; Fischer, L.J. The metabolism of diethylstilbestro. Crit. Rev. Biochem., 1981, 10(3), 171-212. doi: 10.3109/10409238109113599
  34. Elhennawy, M.G.; Abdelaleem, E.A.; Zaki, A.A.; Mohamed, W.R. Cinnamaldehyde and hesperetin attenuate TNBS‐induced ulcerative colitis in rats through modulation of the JAk2/STAT3/SOCS3 pathway. J. Biochem. Mol. Toxicol., 2021, 35(5), e22730. doi: 10.1002/jbt.22730 PMID: 33522063
  35. Ren, H.; Hao, J.; Liu, T.; Zhang, D.; Lv, H.; Song, E.; Zhu, C. Hesperetin suppresses inflammatory responses in lipopolysaccharide-induced RAW 264.7 Cells via the Inhibition of NF-κB and activation of Nrf2/HO-1 pathways. Inflammation, 2016, 39(3), 964-973. doi: 10.1007/s10753-016-0311-9 PMID: 26994999
  36. Cho, J. Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin. Arch. Pharm. Res., 2006, 29(8), 699-706. doi: 10.1007/BF02968255 PMID: 16964766
  37. Svanfelt, J.; Eriksson, J.; Kronberg, L. Analysis of thyroid hormones in raw and treated waste water. J. Chromatogr. A, 2010, 1217(42), 6469-6474. doi: 10.1016/j.chroma.2010.08.032 PMID: 20850122
  38. Noda, M. Thyroid hormone in the CNS: Contribution of neuron–glia interaction. Vitam. Horm., 2018, 106, 313-331. doi: 10.1016/bs.vh.2017.05.005 PMID: 29407440
  39. Mielgo, V.; Valls i Soler, A.; Rey-Santano, C. Dobutamine in paediatric population: A systematic review in juvenile animal models. PLoS One, 2014, 9(4), e95644. doi: 10.1371/journal.pone.0095644 PMID: 24755688
  40. Hu, Q.; Guan, X.Q.; Song, L.L.; Wang, H.N.; Xiong, Y.; Liu, J.L.; Yin, H.; Cao, Y.F.; Hou, J.; Yang, L.; Ge, G.B. Inhibition of pancreatic lipase by environmental xenoestrogens. Ecotoxicol. Environ. Saf., 2020, 192, 110305. doi: 10.1016/j.ecoenv.2020.110305 PMID: 32070782
  41. Maitreesophone, P.; Khine, H.E.E.; Nealiga, J.Q.L.; Kongkatitham, V.; Panuthai, P.; Chaotham, C.; Likhitwitayawuid, K.; Sritularak, B. α-Glucosidase and pancreatic lipase inhibitory effects and anti-adipogenic activity of dendrofalconerol B, a bisbibenzyl from Dendrobium harveyanum. S. Afr. J. Bot., 2022, 146, 187-195. doi: 10.1016/j.sajb.2021.10.025
  42. Türk, E.; Ozan Tekeli, I.; Özkan, H.; Uyar, A.; Cellat, M.; Kuzu, M.; Yavas, I.; Alizadeh Yegani, A.; Yaman, T.; Güvenç, M. The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats. Andrologia, 2021, 53(2), e13930. doi: 10.1111/and.13930 PMID: 33368464
  43. Taskin, T.; Kahvecioglu, D.; Turkoglu, A.; Dogan, A.; Kuzu, M.; Turkoğlu, A. In vitro biological activities of different extracts from alcea dissecta. Clin. Exp. Heal. Sci., 2022, 12(1), 53-60.
  44. Gishen, N.Z.; Taddese, S.; Zenebe, T.; Dires, K.; Tedla, A.; Mengiste, B.; Shenkute, D.; Tesema, A.; Shiferaw, Y.; Lulekal, E. In vitro antimicrobial activity of six Ethiopian medicinal plants against Staphylococcus aureus, Escherichia coli and Candida albicans. Eur. J. Integr. Med., 2020, 36, 101121. doi: 10.1016/j.eujim.2020.101121
  45. Amin Huseen, N.H. Docking Study of naringin binding with COVID-19 main protease enzyme. Iraqi J. Pharm Sci., 2020, 29(2), 231-238. doi: 10.31351/vol29iss2pp231-238
  46. Rasouli, H.; Hosseini-Ghazvini, S.M.B.; Adibi, H.; Khodarahmi, R. Differential α-amylase/α-glucosidase inhibitory activities of plant-derived phenolic compounds: A virtual screening perspective for the treatment of obesity and diabetes. Food Funct., 2017, 8(5), 1942-1954. doi: 10.1039/C7FO00220C PMID: 28470323
  47. Kuzu, M.; Kandemir, F.M.; Yıldırım, S.; Çağlayan, C.; Küçükler, S. Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin. Environ. Sci. Pollut. Res. Int., 2021, 28(9), 10818-10831. doi: 10.1007/s11356-020-11327-5 PMID: 33099738
  48. Turk, E.; Kandemir, F.M.; Yildirim, S.; Caglayan, C.; Kucukler, S.; Kuzu, M. Protective effect of hesperidin on sodium arsenite-induced nephrotoxicity and hepatotoxicity in rats. Biol. Trace Elem. Res., 2019, 189(1), 95-108. doi: 10.1007/s12011-018-1443-6 PMID: 30066062
  49. Li, B.; Huang, A.L.; Zhang, Y.L.; Li, Z.; Ding, H.W.; Huang, C.; Meng, X.M.; Li, J. Design, synthesis and evaluation of hesperetin derivatives as potential multifunctional anti-alzheimer agents. Molecules, 2017, 22(7), 1067. doi: 10.3390/molecules22071067 PMID: 28672874
  50. Chen, D.W.; Du, Z.; Zhang, C.Z.; Zhang, W.H.; Cao, Y.F.; Sun, H.Z.; Zhu, Z.T.; Yang, K.; Liu, Y.Z.; Zhao, Z.W.; Fu, Z.W.; Gu, W.Q.; Yu, Y.; Fang, Z.Z. The inhibition of UDP-glucuronosyltransferases (UGTs) by tetraiodothyronine (T4) and triiodothyronine (T3). Xenobiotica, 2018, 48(3), 250-257. doi: 10.1080/00498254.2017.1304593 PMID: 28285550
  51. Fu, A.L.; Zhou, C.Y.; Chen, X. Thyroid hormone prevents cognitive deficit in a mouse model of Alzheimer’s disease. Neuropharmacology, 2010, 58(4-5), 722-729. doi: 10.1016/j.neuropharm.2009.12.020 PMID: 20045708
  52. Kizilbay, G.; Karaman, M. Possible inhibition mechanism of dobutamine hydrochloride as potent inhibitor for human glucose-6-phosphate dehydrogenase enzyme. J. Biomol. Struct. Dyn., 2022, 40(1), 204-212. doi: 10.1080/07391102.2020.1811155 PMID: 32835622
  53. Hassan, M.; Raza, H.; Abbasi, M.A.; Moustafa, A.A.; Seo, S.Y. The exploration of novel Alzheimer’s therapeutic agents from the pool of FDA approved medicines using drug repositioning, enzyme inhibition and kinetic mechanism approaches. Biomed. Pharmacother., 2019, 109, 2513-2526. doi: 10.1016/j.biopha.2018.11.115 PMID: 30551512
  54. Ashrafian, H.; Zadeh, E.H.; Khan, R.H. Review on Alzheimer’s disease: Inhibition of amyloid beta and tau tangle formation. Int. J. Biol. Macromol., 2021, 167, 382-394. doi: 10.1016/j.ijbiomac.2020.11.192 PMID: 33278431
  55. Popescu, I.; Yin, G.; Velmurugan, S.; Erickson, J.R.; Despa, F.; Despa, S. Lower sarcoplasmic reticulum Ca2+ threshold for triggering afterdepolarizations in diabetic rat hearts. Heart Rhythm, 2019, 16(5), 765-772. doi: 10.1016/j.hrthm.2018.11.001 PMID: 30414461
  56. Sugimoto, H.; Ogura, H.; Arai, Y.; Iimura, Y.; Yamanishi, Y. Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor. Jpn. J. Pharmacol., 2002, 89(1), 7-20. doi: 10.1254/jjp.89.7 PMID: 12083745
  57. Syaifie, P.H.; Widya Hemasita, A.; Nugroho, D.W.; Mardliyati, E.; Anshori, I. In Silico investigation of propolis compounds as potential neuroprotective agent. Biointerface Res. Appl. Chem., 2021, 12(6), 8285-8306. doi: 10.33263/BRIAC126.82858306
  58. Vitorović-Todorović, M.; Cvijetić, I.; Zloh, M.; Perdih, A. Molecular recognition of acetylcholinesterase and its subnanomolar reversible inhibitor: A molecular simulations study. J. Biomol. Struct. Dyn., 2022, 40(4), 1671-1691. doi: 10.1080/07391102.2020.1831960 PMID: 33047663
  59. Aleixandre, A.; Gil, J.V.; Sineiro, J.; Rosell, C.M. Understanding phenolic acids inhibition of α-amylase and α-glucosidase and influence of reaction conditions. Food Chem., 2022, 372, 131231. doi: 10.1016/j.foodchem.2021.131231 PMID: 34624776
  60. Li, Y.; Sang, S.; Ren, W.; Pei, Y.; Bian, Y.; Chen, Y.; Sun, H. Inhibition of Histone Deacetylase 6 (HDAC6) as a therapeutic strategy for Alzheimer’s disease: A review (2010-2020). Eur. J. Med. Chem., 2021, 226, 113874. doi: 10.1016/j.ejmech.2021.113874 PMID: 34619465
  61. Padhi, S.; Dash, M.; Behera, A. Nanophytochemicals for the treatment of type II diabetes mellitus: A review. Environ. Chem. Lett., 2021, 19(6), 4349-4373. doi: 10.1007/s10311-021-01283-y

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Bentham Science Publishers