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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Inhibition of Amyloid Fibrillation of HEWL by 4-Methylcoumarin and 4-Methylthiocoumarin Derivatives

Author(s): Shivani Kumar, Manoj Kumar, Yogesh K. Tyagi* and Suresh Kumar*

Volume 22, Issue 2, 2021

Published on: 15 September, 2020

Page: [232 - 244] Pages: 13

DOI: 10.2174/1389201021666200915112849

Price: $65

Abstract

Background: Several human diseases like Parkinson’s, Alzheimer’s disease, and systemic amyloidosis are associated with the misfolding and aggregation of protein molecules.

Objective: The present study demonstrated the comparison of 4-methyl coumarin and 4-methylthiocoumarin derivative for their anti-amyloidogenic and disaggregation activities. The hen egg-white lysozyme is used as a model system to study protein aggregation and disaggregation under in vitro conditions.

Methods: Techniques used in the study were Thioflavin T fluorescence assay, intrinsic fluorescence assay, circular dichroism, transmission electron microscopy, and molecular dynamics.

Results: Fifteen compounds were screened for their anti-amyloidogenic and disaggregation potential. Six compounds significantly inhibited the fibril formation, whereas ten compounds showed disaggregation property of pre-formed fibrils. Under in vitro conditions, the compound C3 and C7 showed significant inhibition of fibril formation in a concentration-dependent manner as compared to control. C3 and C7 demonstrated 93% and 76% inhibition of fibril formation, respectively. Furthermore, C3 and C7 exhibited 83% and 76% disaggregation activity, respectively, of pre-formed HEWL fibrils at their highest concentration. These anti-amyloidogenic and disaggregation potential of C3 and C7 were validated by intrinsic fluorescence, CD, molecular dynamics, and TEM study.

Discussion: 4-methylthiocoumarins derivatives have shown better anti-amyloidogenic activity as compared to 4-methylcoumarin derivatives for both amyloid formation as well as disaggregation of preformed amyloid fibrils. Structurally, the derivatives of 4-methylthiocoumarins (C3 and C7) contain thio group on 2nd position that might be responsible for anti-amyloidogenic activity as compared to 4- methylcoumarin derivatives (C2 and C4).

Conclusion: C3 and C7 are novel 4-methylthiocoumarin derivatives that can be used as a lead for alleviation and symptoms associated with protein aggregation disorders.

Keywords: HEWL, 4-methylcoumarin, 4-methylthiocoumarin, anti-amyloidogenic activity, amyloidosis, amyloid fibril.

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[1]
Chaari, A.; Fahy, C.; Chevillot-Biraud, A.; Rholam, M. Insights into kinetics of agitation-induced aggregation of hen lysozyme under heat and acidic conditions from various spectroscopic methods. PLoS One, 2015, 10(11), e0142095.
[http://dx.doi.org/10.1371/journal.pone.0142095] [PMID: 26571264]
[2]
Alam, P.; Chaturvedi, S.K.; Siddiqi, M.K.; Rajpoot, R.K.; Ajmal, M.R.; Zaman, M.; Khan, R.H. Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases. Sci. Rep., 2016, 6, 26759.
[http://dx.doi.org/10.1038/srep26759] [PMID: 27230476]
[3]
Ramazzotti, M.; Melani, F.; Marchi, L.; Mulinacci, N.; Gestri, S.; Tiribilli, B.; Degl’Innocenti, D. Mechanisms for the inhibition of amyloid aggregation by small ligands. Biosci. Rep., 2016, 36(5), e00385.
[http://dx.doi.org/10.1042/BSR20160101] [PMID: 27512096]
[4]
Roqanian, S.; Meratan, A.A.; Ahmadian, S.; Shafizadeh, M.; Ghasemi, A.; Karami, L. Polyphenols protect mitochondrial membrane against permeabilization induced by HEWL oligomers: Possible mechanism of action. Int. J. Biol. Macromol., 2017, 103, 709-720.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.05.130] [PMID: 28545969]
[5]
Ow, S.Y.; Dunstan, D.E. The effect of concentration, temperature and stirring on hen egg white lysozyme amyloid formation. Soft Matter, 2013, 9(40), 9692-9701.
[http://dx.doi.org/10.1039/c3sm51671g] [PMID: 26029778]
[6]
Mariño, L.; Pauwels, K.; Casasnovas, R.; Sanchis, P.; Vilanova, B.; Muñoz, F.; Donoso, J.; Adrover, M. Ortho-methylated 3-hydroxypyridines hinder hen egg-white lysozyme fibrillogenesis. Sci. Rep., 2015, 5, 12052.
[http://dx.doi.org/10.1038/srep12052] [PMID: 26169912]
[7]
Härd, T.; Lendel, C. Inhibition of amyloid formation. J. Mol. Biol., 2012, 421(4-5), 441-465.
[http://dx.doi.org/10.1016/j.jmb.2011.12.062] [PMID: 22244855]
[8]
Srikrishna, D.; Godugu, C.; Dubey, P.K. A review on pharmacological properties of coumarins. Mini Rev. Med. Chem., 2018, 18(2), 113-141.
[http://dx.doi.org/10.2174/1389557516666160801094919] [PMID: 27488585]
[9]
Kumar, K.A.; Renuka, N.; Pavithra, G.; Kumar, G.V. Comprehensive review on coumarins: Molecules of potential chemical and pharmacological interest. J. Chem. Pharm. Res., 2015, 7(9), 67-81.
[10]
Hamulakova, S.; Janovec, L.; Soukup, O.; Jun, D.; Kuca, K. Synthesis, in vitro acetylcholinesterase inhibitory activity and molecular docking of new acridine-coumarin hybrids. Int. J. Biol. Macromol., 2017, 104(Pt A), 333-338.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.06.006] [PMID: 28601645]
[11]
de Souza, L.G.; Rennã, M.N.; Figueroa-Villar, J.D. Coumarins as cholinesterase inhibitors: A review. Chem. Biol. Interact., 2016, 254, 11-23.
[http://dx.doi.org/10.1016/j.cbi.2016.05.001] [PMID: 27174134]
[12]
Baruah, P.; Basumatary, G.; Yesylevskyy, S.O.; Aguan, K.; Bez, G.; Mitra, S. Novel coumarin derivatives as potent acetylcholinesterase inhibitors: Insight into efficacy, mode and site of inhibition. J. Biomol. Struct. Dyn., 2019, 37(7), 1750-1765.
[http://dx.doi.org/10.1080/07391102.2018.1465853] [PMID: 29663860]
[13]
Raza, A.; Saeed, A.; Ibrar, A.; Muddassar, M.; Khan, A.A.; Iqbal, J. Pharmacological evaluation and docking studies of 3-thiadiazolyl-and thioxo-1, 2, 4-triazolylcoumarin derivatives as cholinesterase inhibitors. ISRN Pharmacol., 2012.
[14]
Borg, S.; Vollinga, R.C.; Labarre, M.; Payza, K.; Terenius, L.; Luthman, K. Design, synthesis, and evaluation of Phe-Gly mimetics: Heterocyclic building blocks for pseudopeptides. J. Med. Chem., 1999, 42(21), 4331-4342.
[http://dx.doi.org/10.1021/jm990197+] [PMID: 10543877]
[15]
Goel, A.; Prasad, A.K.; Parmar, V.S.; Ghosh, B.; Saini, N. Apoptogenic effect of 7,8-diacetoxy-4-methylcoumarin and 7,8-diacetoxy-4-methylthiocoumarin in human lung adenocarcinoma cell line: Role of NF-kappaB, Akt, ROS and MAP kinase pathway. Chem. Biol. Interact., 2009, 179(2-3), 363-374.
[http://dx.doi.org/10.1016/j.cbi.2008.10.060] [PMID: 19061872]
[16]
De Poi, L.P.; Pitzurra, M.; Negri, M.D.E. Antibacterial properties of thiocoumarin and its 7-substituted derivatives. Boll. Chim. Farm., 1962, 101, 376-379.
[PMID: 13884474]
[17]
Mokrov, G.V.; Voronina, T.A.; Litvinova, S.A.; Kovalev, I.G.; Nerobkova, L.N.; Durnev, A.D.; Seredenin, S.B. Synthesis and anticonvulsant activity of 4-amino-3-nitro-1-thiocoumarins and 4-amino-3-nitroquinolin-2-ones. Pharm. Chem. J., 2019, 53(3), 194-200.
[http://dx.doi.org/10.1007/s11094-019-01978-1]
[18]
Raj, H.G.; Parmar, V.S.; Jain, S.C.; Goel, S. Poonam; Himanshu; Malhotra, S.; Singh, A.; Olsen, C.E.; Wengel, J. Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part I: Dioxygenated 4-methyl coumarins as superb antioxidant and radical scavenging agents. Bioorg. Med. Chem., 1998, 6(6), 833-839.
[http://dx.doi.org/10.1016/S0968-0896(98)00043-1] [PMID: 9681149]
[19]
Tyagi, Y.K.; Tyagi, S.; Raj, H.G.; Gupta, R.K. Synthesis of novel 4-methylcoumarins and comparative specificities of substituted derivatives for acetoxy drug: Protein transacetylase. Sci. Pharm., 2008, 76(3), 395-414.
[http://dx.doi.org/10.3797/scipharm.0805-08]
[20]
Tyagi, Y.K.; Shvetambri, T.; Raj, H.G.; Gupta, R.K. In vitro antioxidant activity evaluation of 4-methyl coumarin derivatives. Asian J. Chem., 2010, 22(5), 3622-3628.
[21]
Joloudar, T.N.; Saboury, A.A.; Shasaltaneh, M.D.; Bahramikia, S.; Ebrahimi, M.A.; Ghasemi, A. Inhibitory effect of safranal and crocin, two principle compounds of Crocus sativus, on fibrillation of lysozyme. J. Iran ChemSoc., 2017, 14(11), 2407-2416.
[http://dx.doi.org/10.1007/s13738-017-1175-0]
[22]
Vieira, M.N.; Figueroa-Villar, J.D.; Meirelles, M.N.L.; Ferreira, S.T.; De Felice, F.G. Small molecule inhibitors of lysozyme amyloid aggregation. Cell Biochem. Biophys., 2006, 44(3), 549-553.
[http://dx.doi.org/10.1385/CBB:44:3:549] [PMID: 16679543]
[23]
Mahdavimehr, M.; Meratan, A.A.; Ghobeh, M.; Ghasemi, A.; Saboury, A.A.; Nemat-Gorgani, M. Inhibition of HEWL fibril formation by taxifolin: Mechanism of action. PLoS One, 2017, 12(11), e0187841.
[http://dx.doi.org/10.1371/journal.pone.0187841] [PMID: 29131828]
[24]
Kuo, C.T.; Chen, Y.L.; Hsu, W.T.; How, S.C.; Cheng, Y.H.; Hsueh, S.S.; Liu, H.S.; Lin, T.H.; Wu, J.W.; Wang, S.S. Investigating the effects of erythrosine B on amyloid fibril formation derived from lysozyme. Int. J. Biol. Macromol., 2017, 98, 159-168.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.01.110] [PMID: 28137461]
[25]
Humblet-Hua, N.P.; Sagis, L.M.; van der Linden, E. Effects of flow on Hen Egg White Lysozyme (HEWL) fibril formation: Length distribution, flexibility, and kinetics. J. Agric. Food Chem., 2008, 56(24), 11875-11882.
[http://dx.doi.org/10.1021/jf803377n] [PMID: 19035658]
[26]
Lieu, V.H.; Wu, J.W.; Wang, S.S.S.; Wu, C.H. Inhibition of amyloid fibrillization of hen egg-white lysozymes by rifampicin and p-benzoquinone. Biotechnol. Prog., 2007, 23(3), 698-706.
[http://dx.doi.org/10.1021/bp060353n] [PMID: 17492832]
[27]
Diamond, R. Real-space refinement of the structure of hen egg-white lysozyme. J. Mol. Biol., 1974, 82(3), 371-391.
[http://dx.doi.org/10.1016/0022-2836(74)90598-1] [PMID: 4856347]
[28]
Kaminski, G.A.; Friesner, R.A.; Tirado-Rives, J.; Jorgensen, W.L. Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J. Phys. Chem. B, 2001, 105(28), 6474-6487.
[http://dx.doi.org/10.1021/jp003919d]
[29]
Garbuzynskiy, S.O.; Lobanov, M.Y.; Galzitskaya, O.V. Fold amyloid: A method of prediction of amyloidogenic regions from protein sequence. Bioinformatics, 2010, 26(3), 326-332.
[http://dx.doi.org/10.1093/bioinformatics/btp691] [PMID: 20019059]
[30]
Shelley, J.C.; Cholleti, A.; Frye, L.L.; Greenwood, J.R.; Timlin, M.R.; Uchimaya, M. Epik: A software program for pK(a) prediction and protonation state generation for drug-like molecules. J. Comput. Aided Mol. Des., 2007, 21(12), 681-691.
[http://dx.doi.org/10.1007/s10822-007-9133-z] [PMID: 17899391]
[31]
Watts, K.S.; Dalal, P.; Murphy, R.B.; Sherman, W.; Friesner, R.A.; Shelley, J.C. ConfGen: A conformational search method for efficient generation of bioactive conformers. J. Chem. Inf. Model., 2010, 50(4), 534-546.
[http://dx.doi.org/10.1021/ci100015j] [PMID: 20373803]
[32]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K.; Shaw, D.E.; Francis, P.; Shenkin, P.S. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem., 2004, 47(7), 1739-1749.
[http://dx.doi.org/10.1021/jm0306430] [PMID: 15027865]
[33]
Bowers, K.J.; Chow, D.E.; Xu, H.; Dror, R.O.; Eastwood, M.P.; Gregersen, B.A.; Salmon, J.K. Scalable algorithms for molecular dynamics simulations on commodity clusters. In: SC’06: Proceedings of the 2006 ACM/IEEE Conference on Supercomputing IEEE; , 2006; pp. 43-43.
[http://dx.doi.org/10.1109/SC.2006.54]
[34]
Jorgensen, W.L.; Chandrasekhar, J.; Madura, J.D.; Impey, R.W.; Klein, M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys., 1983, 79(2), 926-935.
[http://dx.doi.org/10.1063/1.445869]
[35]
Tuckerman, M.B.B.J.M.; Berne, B.J.; Martyna, G.J. Reversible multiple time scale molecular dynamics. J. Chem. Phys., 1992, 97(3), 1990-2001.
[http://dx.doi.org/10.1063/1.463137]
[36]
Martyna, G.J.; Klein, M.L.; Tuckerman, M. Nosé-Hoover chains: The canonical ensemble via continuous dynamics. J. Chem. Phys., 1992, 97(4), 2635-2643.
[http://dx.doi.org/10.1063/1.463940]
[37]
Martyna, G.J.; Tobias, D.J.; Klein, M.L. Constant pressure molecular dynamics algorithms. J. Chem. Phys., 1994, 101(5), 4177-4189.
[http://dx.doi.org/10.1063/1.467468]
[38]
Darden, T.; York, D.; Pedersen, L. Particle mesh Ewald: An N⋅ log (N) method for Ewald sums in large systems. J. Chem. Phys., 1993, 98(12), 10089-10092.
[http://dx.doi.org/10.1063/1.464397]
[39]
Daina, A.; Michielin, O.; Zoete, V. Swiss ADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7, 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[40]
PreADMET, version 2.0. Bioinformatics and Molecular Design Research Center, Seoul, Korea, 2008.http://preadmet.bmdrc.org
[41]
Brudar, S.; Hribar-Lee, B. The role of buffers in wild-type HEWL amyloid fibril formation mechanism. Biomolecules, 2019, 9(2), 65.
[http://dx.doi.org/10.3390/biom9020065] [PMID: 30769878]
[42]
Rambaran, R.N.; Serpell, L.C. Amyloid fibrils: Abnormal protein assembly. Prion, 2008, 2(3), 112-117.
[http://dx.doi.org/10.4161/pri.2.3.7488] [PMID: 19158505]
[43]
Ulicna, K.; Bednarikova, Z.; Hsu, W.T.; Holztragerova, M.; Wu, J.W.; Hamulakova, S.; Wang, S.S.; Gazova, Z. Lysozyme amyloid fibrillization in presence of tacrine/acridone-coumarin heterodimers. Colloids Surf. B Biointerfaces, 2018, 166, 108-118.
[http://dx.doi.org/10.1016/j.colsurfb.2018.03.010] [PMID: 29550545]
[44]
Soto-Ortega, D.D.; Murphy, B.P.; Gonzalez-Velasquez, F.J.; Wilson, K.A.; Xie, F.; Wang, Q.; Moss, M.A. Inhibition of amyloid-β aggregation by coumarin analogs can be manipulated by functionalization of the aromatic center. Bioorg. Med. Chem., 2011, 19(8), 2596-2602.
[http://dx.doi.org/10.1016/j.bmc.2011.03.010] [PMID: 21458277]
[45]
Kisilevsky, R.; Lemieux, L.J.; Fraser, P.E.; Kong, X.; Hultin, P.G.; Szarek, W.A. Arresting amyloidosis in vivo using small-molecule anionic sulphonates or sulphates: Implications for Alzheimer’s disease. Nat. Med., 1995, 1(2), 143-148.
[http://dx.doi.org/10.1038/nm0295-143] [PMID: 7585011]
[46]
Zhao, C.; Rakesh, K.P.; Ravidar, L.; Fang, W.Y.; Qin, H.L. Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: A critical review. Eur. J. Med. Chem., 2019, 162, 679-734.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.017] [PMID: 30496988]
[47]
Chong, X.; Sun, L.; Sun, Y.; Chang, L.; Chang, A.K.; Lu, X.; Zhou, X.; Liu, J.; Zhang, B.; Jones, G.W.; He, J. Insights into the mechanism of how Morin suppresses amyloid fibrillation of hen egg white lysozyme. Int. J. Biol. Macromol., 2017, 101, 321-325.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.03.107] [PMID: 28341174]
[48]
Swetha, R.; Kumar, D.; Gupta, S.K.; Ganeshpurkar, A.; Singh, R.; Gutti, G.; Kumar, D.; Jana, S.; Krishnamurthy, S.; Singh, S.K. Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer’s disease. Future Med. Chem., 2019, 11(24), 3161-3178.
[http://dx.doi.org/10.4155/fmc-2019-0106] [PMID: 31838895]
[49]
Ishtikhar, M.; Usmani, S.S.; Gull, N.; Badr, G.; Mahmoud, M.H.; Khan, R.H. Inhibitory effect of copper nanoparticles on rosin modified surfactant induced aggregation of lysozyme. Int. J. Biol. Macromol., 2015, 78, 379-388.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.03.069] [PMID: 25863156]
[50]
Alam, P.; Chaturvedi, S.K.; Anwar, T.; Siddiqi, M.K.; Ajmal, M.R.; Badr, G.; Khan, R.H. Biophysical and molecular docking insight into the interaction of cytosine β-D arabinofuranoside with human serum albumin. J. Lumin., 2015, 164, 123-130.
[http://dx.doi.org/10.1016/j.jlumin.2015.03.011]
[51]
Das, T.; Kolli, V.; Karmakar, S.; Sarkar, N. Functionalisation of polyvinylpyrrolidone on gold nanoparticles enhances its anti-amyloidogenic propensity towards hen egg white lysozyme. Biomedicines, 2017, 5(2), 19.
[PMID: 28536362]
[52]
Nichol, C.A. Pharmacokinetics: Selectivity of action related to physicochemical properties and kinetic patterns of anticancer drugs. Cancer, 1977, 40(1)(Suppl.), 519-528.
[http://dx.doi.org/10.1002/1097-0142(197707)40:1+<519::AIDCNCR2820400718>3.0.CO;2-4] [PMID: 328135]

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