The therapeutic value of thiazole and thiazolidine derivatives in Alzheimer's disease: a systematic literature review

Zahra Abdollahi, Mojgan Nejabat, Khalil Abnous, Farzin Hadizadeh

Abstract


Background and purpose: Alzheimer's disease (AD) is a common neurodegenerative disease and the fifth leading cause of death among the elderly. The development of drugs for AD treatment is based on inhibiting cholinesterase (ChE) activity and inhibiting amyloid-beta peptide and tau protein aggregations. Many in vitro findings have demonstrated that thiazole- and thiazolidine-based compounds have a good inhibitory effect on ChE and other elements involved in the AD pathogenicity cascade.

Experimental approach: In the present review, we collected available documents to verify whether these synthetic compounds can be a step forward in developing new medications for AD. A systematic literature search was performed in major electronic databases in April 2021. Twenty-eight relevant in vitro and in vivo studies were found and used for data extraction.

Findings/Results: Findings demonstrated that thiazole- and thiazolidine-based compounds could ameliorate AD's pathologic condition by affecting various targets, including inhibition of ChE activity, amyloid-beta, and tau aggregation in addition to cyclin-dependent kinase 5/p25, beta-secretase-1, cyclooxygenase, and glycogen synthase kinase-3β.

Conclusion and implications: Due to multitarget effects at micromolar concentration, this review demonstrated that these synthetic compounds could be considered promising candidates for developing                  anti-Alzheimer drugs.


Keywords


Alzheimer's disease; Amyloid beta; Cholinesterase; Glycogen synthase kinase; Thiazolidine; Thiazole

Full Text:

PDF

References


Alzheimer’s association report. 2021 Alzheimer's disease facts and figures. Alzheimers Dement. 2021;17(3):327-406.DOI: 10.1002/alz.12328.

Hassanzadeh A, Yegdaneh A, Rabbani M. Effects of hydroalcoholic, methanolic, and hexane extracts of brown algae Sargassum angustifolium on scopolamine-induced memory impairment and learning deficit in rodents. Res Pharm Sci, 2023;18(3):292-302.DOI: 10.4103/1735-5362.371585.

Stix G. Alzheimer's: forestalling the darkness. Sci Am. 2010;302(6):50-57.DOI: 10.1038/scientificamerican0610-50.

Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013;80(19):1778-1183.DOI: 10.1212/WNL.0b013e31828726f5.

Teymuori M, Yegdaneh A, Rabbani M. Effects of Piper nigrum fruit and Cinnamum zeylanicum bark alcoholic extracts, alone and in combination, on scopolamine-induced memory impairment in mice. Res Pharm Sci. 2021;16(5):474-481.DOI: 10.4103/1735-5362.323914.

Whitwell JL, Jack CR, Przybelski SA, Parisi JE, Senjem ML, Boeve BF, et al. Temporoparietal atrophy: a marker of AD pathology independent of clinical diagnosis. Neurobiol Aging. 2011;32(9):1531-1541.DOI 10.1016/j.neurobiolaging.2009.10.012.

Lin L, Zheng LJ, Zhang LJ. Neuroinflammation, gut microbiome, and Alzheimer’s disease. Mol Neurobiol. 2018;55(11):8243-8250.DOI: 10.1007/s12035-018-0983-2.

Mirzaee M, Semnani S, Roshandel G, Nejabat M, HesariH Z, Joshaghani H. Strontium and antimony serum levels in healthy individuals living in high‐and low‐risk areas of esophageal cancer. J Clin Lab Anal. 2020;34(7):e23269,1-8.DOI: 10.1002/jcla.23269.

Engel M, Do-Ha D, MunozL SS, Ooi L. Common pitfalls of stem cell differentiation: a guide to improving protocols for neurodegenerative disease models and research. Cell Mol Life Sci. 2016;73(19):3693-3709.DOI: 10.1007/s00018-016-2265-3.

Jones S V, Kounatidis I. Nuclear factor-kappa B and Alzheimer disease, unifying genetic and environmental risk factors from cell to humans. Front Immunol. 2017;8:1805,1-9.DOI: 10.3389/fimmu.2017.01805.

Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1(1):a006189,1-24.DOI: 10.1101/cshperspect.a006189.

Shega JW, Ellner L, Lau DT, Maxwell L. Cholinesterase inhibitor and N-methyl-D-aspartic acid receptor antagonist use in older adults with end-stage dementia: a survey of hospice medical directors. J Palliat Med. 2009;12(9):779-783.DOI: 10.1089/jpm.2009.0059.

Pashaei H, Rouhani A, Nejabat M, Hadizadeh F, Mirzaei S, Nadri H, et al. Synthesis and molecular dynamic simulation studies of novel N-(1-benzylpiperidin-4-yl) quinoline-4-carboxamides as potential acetylcholinesterase inhibitors. J Mol Struct. 2021;1244:130919,1-10.DOI: 10.1016/j.molstruc.2021.130919.

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1-e34.DOI: 10.1016/j.jclinepi.2009.06.006.

da Silva DS, Soares MSP, Martini F, Pesarico AP, de Mattos BDS, de Souza AA, et al. In vitro effects of 2-{4-[methylthio(methylsulfonyl)]phenyl}-3-substitutedthiazolidin-4-ones on the acetyl-cholinesterase activity in rat brain and lymphocytes: isoform selectivity, kinetic analysis, and molecular docking. Neurochem Res. 2020;45(2):241-253.DOI: 10.1007/s11064-019-02929-8.

Rynearson KD, Buckle RN, Herr RJ, Mayhew NJ, Chen X, Paquette WD, et al. Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators. Bioorg Med Chem. 2020;28(22):115734,1-24.DOI: 10.1016/j.bmc.2020.115734.

Rynearson KD, Buckle RN, Herr RJ, Mayhew NJ, Chen X, Paquette WD, et al. Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators. Bioorg Med Chem. 2020;28(22):115734,1-24.DOI: 10.1016/j.bmc.2020.115734.

das Neves AM, Berwaldt GA, Avila CT, Goulart TB, Moreira BC, Ferreira TP, et al. Synthesis of thiazolidin-4-ones and thiazinan-4-ones from 1-(2-aminoethyl)pyrrolidine as acetylcholinesterase inhibitors. J Enzyme Inhib Med Chem. 2020;35(1):31-41.DOI: 10.1080/14756366.2019.1680659.

Abdullaha M, Ali M, Kour D, Kumar A, Bharate SB. Discovery of benzo[cd]indol-2-one and benzylidene-thiazolidine-2,4-dione as new classes of NLRP3 inflammasome inhibitors via ER-beta structure based virtual screening. Bioorg Chem. 2020;95:103500,1-22.DOI: 10.1016/j.bioorg.2019.103500.

Petrache AL, Khan AA, Nicholson MW, Monaco A, Kuta-Siejkowska M, Haider S, et al. Selective modulation of alpha5 GABAA receptors exacerbates aberrant inhibition at key hippocampal neuronal circuits in APP mouse model of Alzheimer's disease. Front Cell Neurosci. 2020;14:568194, 1-18.DOI: 10.3389/fncel.2020.568194.

Ghotbi G, Mahdavi M, Najafi Z, Moghadam FH, Hamzeh-Mivehroud M, Davaran S, et al. Design, synthesis, biological evaluation, and docking study of novel dual-acting thiazole-pyridiniums inhibiting acetylcholinesterase and β-amyloid aggregation for Alzheimer’s disease. Bioorg Chem. 2020;103:104186,1-15.DOI: 10.1016/j.bioorg.2020.104186.

Jiang X, Zhou J, Wang Y, Chen L, Duan Y, Huang J, et al. Rational design and biological evaluation of a new class of thiazolopyridyl tetrahydroacridines as cholinesterase and GSK-3 dual inhibitors for Alzheimer’s disease. Eur J Med Chem. 2020;207:112751,1-16.DOI: 10.1016/j.ejmech.2020.112751.

Noori MS, Bhatt PM, Courreges MC, Ghazanfari D, Cuckler C, Orac CM, et al. Identification of a novel selective and potent inhibitor of glycogen synthase kinase-3. Am J Physiol Cell Physiol. 2019;317(6):C1289-C1303.DOI: 10.1152/ajpcell.00061.2019.

Salehi N, Mirjalili BBF, Nadri H, Abdolahi Z, Forootanfar H, Samzadeh-Kermani A, et al. Synthesis and biological evaluation of new N-benzylpyridinium-based benzoheterocycles as potential anti-Alzheimer's agents. Bioorg Chem. 2019;83:559-568.DOI: 10.1016/j.bioorg.2018.11.010.

Jonczyk J, Lodarski K, Staszewski M, Godyn J, Zareba P, Soukup O, et al. Search for multifunctional agents against Alzheimer's disease among non-imidazole histamine H3 receptor ligands. In vitro and in vivo pharmacological evaluation and computational studies of piperazine derivatives. Bioorg Chem. 2019;90:103084,1-39.DOI: 10.1016/j.bioorg.2019.103084.

Selnick HG, Hess JF, Tang C, Liu K, Schachter JB, Ballard JE, et al. Discovery of MK-8719, a potent O-GlcNAcase inhibitor as a potential treatment for tauopathies. J Med Chem. 2019;62(22):10062-10097.DOI: 10.1021/acs.jmedchem.9b01090.

Sagar SR, Singh DP, Das RD, Panchal NB, Sudarsanam V, Nivsarkar M, et al. Pharmacological investigation of quinoxaline-bisthiazoles as multitarget-directed ligands for the treatment of Alzheimer's disease. Bioorg Chem. 2019;89:102992,1-43.DOI: 10.1016/j.bioorg.2019.102992.

Rajeshwari R, Chand K, Candeias E, Cardoso SM, Chaves S, Santos MA. New multitarget hybrids bearing tacrine and phenylbenzothiazole motifs as potential drug candidates for Alzheimer's disease. Molecules. 2019;24(3):587,1-15.DOI: 10.3390/molecules24030587.

Aitken L, Benek O, McKelvie BE, Hughes RE, Hroch L, Schmidt M, et al. Novel benzothiazole-based ureas as 17beta-HSD10 inhibitors, a potential Alzheimer's disease treatment. Molecules. 2019;24(15):2757,1-25.DOI: 10.3390/molecules24152757.

Gandini A, Bartolini M, Tedesco D, Martinez-Gonzalez L, Roca C, Campillo NE, et al. Tau-centric multitarget approach for Alzheimer's disease: development of first-in-class dual glycogen synthase kinase 3beta and tau-aggregation inhibitors. J Med Chem. 2018;61(17):7640-7656.

DOI: 10.1021/acs.jmedchem.8b00610.

Sagar SR, Singh DP, Panchal NB, Das RD, Pandya DH, Sudarsanam V, et al. Thiazolyl-thiadiazines as beta site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibitors and anti-inflammatory agents: multitarget-directed ligands for the efficient management of Alzheimer's Disease. ACS Chem Neurosci. 2018;9(7):1663-1679.DOI: 10.1021/acschemneuro.8b00063.

Yan G, Hao L, Niu Y, Huang W, Wang W, Xu F, et al. 2-Substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamides as BACE1 inhibitors: synthesis, biological evaluation and docking studies. Eur J Med Chem. 2017;137:462-475.DOI: 10.1016/j.ejmech.2017.06.020.

Shidore M, Machhi J, Shingala K, Murumkar P, Sharma MK, Agrawal N, et al. Benzylpiperidine-linked diarylthiazoles as potential anti-Alzheimer's agents: synthesis and biological evaluation. J Med Chem. 2016;59(12):5823-5846.DOI: 10.1021/acs.jmedchem.6b00426.

Luo J, Lee SH, VandeVrede L, Qin Z, Ben Aissa M, Larson J, et al. A multifunctional therapeutic approach to disease modification in multiple familial mouse models and a novel sporadic model of Alzheimer's disease. Mol Neurodegener. 2016;11:35,1-14.DOI: 10.1186/s13024-016-0103-6.

Sun ZQ, Tu LX, Zhuo FJ, Liu SX. Design and discovery of novel thiazole acetamide derivatives as anticholinesterase agent for possible role in the management of Alzheimer's. Bioorg Med Chem Lett. 2016;26(3):747-750.DOI: 10.1016/j.bmcl.2016.01.001.

Turan-Zitouni G, Ozdemir A, Kaplancikli ZA, Altintop MD, Temel HE, Ciftci GA. Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors. J Enzyme Inhib Med Chem. 2013;28(3):509-514.DOI: 10.3109/14756366.2011.653355.

Keri RS, Quintanova C, Marques SM, Esteves AR, Cardoso SM, Santos MA. Design, synthesis and neuroprotective evaluation of novel tacrine-benzothiazole hybrids as multi-targeted compounds against Alzheimer’s disease. Bioorg Med Chem. 2013;21(15):4559-4569.DOI: 10.1016/j.bmc.2013.05.028.

Geng J, Li M, Wu L, Ren J, Qu X. Liberation of copper from amyloid plaques: making a risk factor useful for Alzheimer's disease treatment. J Med Chem. 2012;55(21):9146-9155.DOI: 10.1021/jm3003813.

Wang Y, Wang F, Yu JP, Jiang FC, Guan XL, Wang CM, et al. Novel multipotent phenylthiazole-tacrine hybrids for the inhibition of cholinesterase activity, beta-amyloid aggregation and Ca2+ overload. Bioorg Med Chem. 2012;20(21): 6513-6522.DOI: 10.1016/j.bmc.2012.08.040.

Lagoja I, Pannecouque C, Griffioen G, Wera S, Rojasdelaparra VM, Van Aerschot A. Substituted 2-aminothiazoles are exceptional inhibitors of neuronal degeneration in tau-driven models of Alzheimer's disease. Eur J Pharm Sci. 2011;43(5):386-392.DOI: 10.1016/j.ejps.2011.05.014.

Zare-Zardini H, Ferdowsian F, Soltaninejad H, Ghorani Azam A, Soleymani S, Zare-Shehneh M, et al. Application of nanotechnology in biomedicine: a major focus on cancer therapy. J Nano Res. 2015;35:55-66.DOI: 10.4028/www.scientific.net/JNanoR.35.55.

Shiradkar MR, Akula KC, Dasari V, Baru V, Chiningiri B, Gandhi S, et al. Clubbed thiazoles by MAOS: a novel approach to cyclin-dependent kinase 5/p25 inhibitors as a potential treatment for Alzheimer's disease. Bioorg Med Chem. 2007;15(7):2601-2610.DOI: 10.1016/j.bmc.2007.01.043.

Pickhardt M, Larbig G, Khlistunova I, Coksezen A, Meyer B, Mandelkow EM, et al. Phenylthiazolyl-hydrazide and its derivatives are potent inhibitors of tau aggregation and toxicity in vitro and in cells. Biochemistry. 2007;46(35):10016-10023.DOI: 10.1021/bi700878g.

Gulisano W, Maugeri D, Baltrons MA, Fa M, Amato A, Palmeri A, et al. Role of amyloid-beta and tau proteins in Alzheimer's disease: confuting the amyloid cascade. J Alzheimers Dis. 2018;64(s1):S611-S631.DOI: 10.3233/JAD-179935.

Pickett EK, Herrmann AG, McQueen J, Abt K, Dando O, Tulloch J, et al. Amyloid beta and tau cooperate to cause reversible behavioral and transcriptional deficits in a model of Alzheimer's disease. Cell Rep. 2019;29(11):3592-3604. e5.DOI: 10.1016/j.celrep.2019.11.044.

Chen J, Fan A, Li S, Xiao Y, Fu Y, Chen JS, et al. APP mediates tau uptake and its overexpression leads to the exacerbated tau pathology. Cell Mol Life Sci. 2023;80(5):123.DOI: 10.1007/s00018-023-04774-z.

Cole SL, Vassar R. The Alzheimer's disease beta-secretase enzyme, BACE1. Mol Neurodegener. 2007;2:22,1-25.DOI: 10.1186/1750-1326-2-22.

Chico LK, Van Eldik LJ, Watterson DM. Targeting protein kinases in central nervous system disorders. Nat Rev Drug Discov. 2009;8(11):892-909.DOI: 10.1038/nrd2999.

Masand N, Gupta SP, Khosa RL, Patil VM. Heterocyclic secretase inhibitors for the treatment of Alzheimer's disease: an overview. Cent Nerv Syst Agents Med Chem. 2017;17(1):3-25.DOI: 10.2174/1570159X13666151029105752.

Sharma PC, Sinhmar A, Sharma A, Rajak H, Pathak DP. Medicinal significance of benzothiazole scaffold: an insight view. J Enzyme Inhib Med Chem. 2012;28(2):240-266.DOI: 10.3109/14756366.2012.720572.

Iqbal J, al-Rashida M, Babar A, Hameed A, Khan MS, Munawar MA, et al. Cholinesterase inhibitory activities of N-phenylthiazol-2-amine derivatives and their molecular docking studies. Med Chem. 2015;11(5):489-496.DOI: 10.2174/1573406411666141230104536.

Tang W, Lin C, Yu Q, Zhang D, Liu Y, Zhang L, et al. novel medicinal chemistry strategies targeting CDK5 for Drug Discovery. J Med Chem. 2023;66(11):7140-7161.DOI: 10.1021/acs.jmedchem.3c00566.

Rodriguez-Rodriguez C, de Groot SN, Rimola A, Alvarez-Larena A, Lloveras V, Vidal-Gancedo J, et al. Design, selection, and characterization of thioflavin-based intercalation compounds with metal chelating properties for application in Alzheimer's disease. J Am Chem Soc. 2009;131(4):1436-1451.DOI: 10.1021/ja806062g.

Ahmadi A, Roghani M, Noori S, Nahri-Niknafs B. Substituted aminobenzothiazole derivatives of tacrine: synthesis and study on learning and memory impairment in scopolamine-induced model of amnesia in rat. Mini Rev Med Chem. 2019;19(1):72-78.DOI: 10.2174/1389557518666180716122608.

Demirayak Ş, Şahin Z, Ertaş M, F Bülbül E, Bender C, Biltekin S N, et al. Novel thiazole-piperazine derivatives as potential cholinesterase inhibitors. J Heterocycl Chem. 2019;56(12):3370-3386.DOI: 10.1002/jhet.3734.

Raza R, Saeed A, Arif M, Mahmood S, Muddassar M, Raza A, et al. Synthesis and biological evaluation of 3-thiazolocoumarinyl Schiff-base derivatives as cholinesterase inhibitors. Chem Biol Drug Des. 2012;80(4):605-615.DOI: 10.1111/j.1747-0285.2012.01435.x.

Ghafoorianfar S, Ghorani-Azam A, Mohajeri SA, Farzin D. Efficiency of nanoparticles for treatment of ocular infections: systematic literature review. J Drug Deliv Sci Technol. 2020;57:101765,1-22.DOI: 10.1016/j.jddst.2020.101765.

Mohseni S, Aghayan M, Ghorani-Azam A, Behdani M, Asoodeh A. Evaluation of antibacterial properties of barium zirconate titanate (BZT) nanoparticle. Braz J Microbiol. 2014;45(4):1393-1399.DOI: 10.1590/s1517-83822014000400033.

Sanchis I, Spinelli R, Aschemacher N, Humpola MV, Siano A. Acetylcholinesterase inhibitory activity of a naturally occurring peptide isolated from Boana pulchella (Anura: Hylidae) and its analogs. Amino Acids. 2020;52(3):387-396.DOI: 10.1007/s00726-019-02815-1.

Riahi-Zanjani B, Balali-Mood M, Es’haghi Z, Asoodeh A, Ghorani-Azam A. Molecular modeling and experimental study of a new peptide-based microextraction fiber for preconcentrating morphine in urine samples. J Mol Model. 2019;25(3):25,1-12.DOI: 10.1007/s00894-019-3925-7.

Asoodeh A, Sepahi S, Ghorani‐Azam A. Purification and modeling amphipathic alpha helical antimicrobial peptides from skin secretions of Euphlyctis cyanophlyctis. Chem Biol Drug Des. 2014;83(4):411-417.DOI: 10.1111/cbdd.12256.

Ghorani-Azam A, Balali-Mood M, Aryan E, Karimi G, Riahi-Zanjani B. Effect of amino acid substitution on biological activity of cyanophlyctin-β and brevinin-2R. J Mol Struct. 2018;1158:14-18.DOI: 10.1016/j.molstruc.2018.01.015.

Baig MH, Ahmad K, Rabbani G, Choi I. Use of peptides for the management of Alzheimer’s disease: diagnosis and inhibition. Front Aging Neurosci. 2018;10:21,1-6.DOI: 10.3389/fnagi.2018.00021.

Nepovimova E, Svobodova L, Dolezal R, Hepnarova V, Junova L, Jun D, et al. Tacrine-benzothiazoles: novel class of potential multitarget anti-Alzheimeŕs drugs dealing with cholinergic, amyloid and mitochondrial systems. Bioorg Chem. 2021;107:104596,1-19.DOI: 10.1016/j.bioorg.2020.104596.


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.