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General Review Article

基于多靶点配体的合理药物设计研究进展

卷 27, 期 28, 2020

页: [4720 - 4740] 页: 21

弟呕挨: 10.2174/0929867327666200102120652

价格: $65

摘要

由于在治疗与耐药性有关的复杂疾病和健康状况方面具有优势，多靶点药物在过去十年中获得了相当多的关注。单靶点药物虽然具有很高的选择性，但不一定疗效更好或副作用更少。因此，开发能够同时作用于多个靶点的药物越来越受到重视，但对药物化学家来说，这是一个巨大的挑战。每个靶标必须有足够的活性和充分特征的药代动力学参数。多靶点药物已被广泛应用于临床，本文将对其进行简要讨论。此外，我们将讨论多靶点配体在指导前瞻性药物重定位中的可能应用。

关键词: 多靶点药物，阿尔茨海默病，帕金森病，癌症，被忽视的热带疾病，药代动力学参数。

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[1]
Csermely, P.; Agoston, V.; Pongor, S. The efficiency of multi-target drugs: the network approach might help drug design. Trends Pharmacol. Sci., 2005, 26(4), 178-182.
[http://dx.doi.org/10.1016/j.tips.2005.02.007] [PMID: 15808341]
[2]
Chen, Z.F.; Orvig, C.; Liang, H. Multi-Target metal-based anticancer agents. Curr. Top. Med. Chem., 2017, 17(28), 3131-3145.
[http://dx.doi.org/10.2174/1568026617666171004155437] [PMID: 28982336]
[3]
Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target directed ligands to combat neurodegenerative diseases. J. Med. Chem., 2008, 51(3), 347-372.
[http://dx.doi.org/10.1021/jm7009364] [PMID: 18181565]
[4]
Kumar, A.; Tiwari, A.; Sharma, A. Changing paradigm from one target one ligand Towards multi-target directed ligand design for key drug targets of Alzheimer Disease: an important role of in silico methods in multi-target directed ligands design. Curr. Neuropharmacol., 2018, 16(6), 726-739.
[http://dx.doi.org/10.2174/1570159X16666180315141643] [PMID: 29542413]
[5]
Bolognesi, M.L. Polypharmacology in a single drug: multitarget drugs. Curr. Med. Chem., 2013, 20(13), 1639-1645.
[http://dx.doi.org/10.2174/0929867311320130004] [PMID: 23410164]
[6]
Bolognesi, M.L.; Rosini, M.; Andrisano, V.; Bartolini, M.; Minarini, A.; Tumiatti, V.; Melchiorre, C. MTDL design strategy in the context of Alzheimer’s disease: from lipocrine to memoquin and beyond. Curr. Pharm. Des., 2009, 15(6), 601-613.
[http://dx.doi.org/10.2174/138161209787315585] [PMID: 19199985]
[7]
Morphy, R.; Rankovic, Z. Designing multiple ligands - medicinal chemistry strategies and challenges. Curr. Pharm. Des., 2009, 15(6), 587-600.
[http://dx.doi.org/10.2174/138161209787315594] [PMID: 19199984]
[8]
Roth, B.L.; Sheffler, D.J.; Kroeze, W.K. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat. Rev. Drug Discov., 2004, 3(4), 353-359.
[http://dx.doi.org/10.1038/nrd1346] [PMID: 15060530]
[9]
Anusuya, S.; Natarajan, J. Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy. Infect. Genet. Evol., 2012, 12(8), 1899-1910.
[http://dx.doi.org/10.1016/j.meegid.2012.08.013] [PMID: 22981928]
[10]
Geldenhuys, W.J.; Van der Schyf, C.J. Rationally designed multi-targeted agents against neurodegenerative diseases. Curr. Med. Chem., 2013, 20(13), 1662-1672.
[http://dx.doi.org/10.2174/09298673113209990112] [PMID: 23410161]
[11]
Luni, C.; Doyle, F.J. Robust multi-drug therapy design and application to insulin resistance in type 2 diabetes. Int. J. Robust. Nonlin., 2011, 21(15), 1730-1741.
[http://dx.doi.org/10.1002/rnc.1756]
[12]
Genin, E.; Hannequin, D.; Wallon, D.; Sleegers, K.; Hiltunen, M.; Combarros, O.; Bullido, M.J.; Engelborghs, S.; De Deyn, P.; Berr, C.; Pasquier, F.; Dubois, B.; Tognoni, G.; Fiévet, N.; Brouwers, N.; Bettens, K.; Arosio, B.; Coto, E.; Del Zompo, M.; Mateo, I.; Epelbaum, J.; Frank-Garcia, A.; Helisalmi, S.; Porcellini, E.; Pilotto, A.; Forti, P.; Ferri, R.; Scarpini, E.; Siciliano, G.; Solfrizzi, V.; Sorbi, S.; Spalletta, G.; Valdivieso, F.; Vepsäläinen, S.; Alvarez, V.; Bosco, P.; Mancuso, M.; Panza, F.; Nacmias, B.; Bossù, P.; Hanon, O.; Piccardi, P.; Annoni, G.; Seripa, D.; Galimberti, D.; Licastro, F.; Soininen, H.; Dartigues, J.F.; Kamboh, M.I.; Van Broeckhoven, C.; Lambert, J.C.; Amouyel, P.; Campion, D. APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol. Psychiatry, 2011, 16(9), 903-907.
[http://dx.doi.org/10.1038/mp.2011.52] [PMID: 21556001]
[13]
Bolognesi, M.L.; Matera, R.; Minarini, A.; Rosini, M.; Melchiorre, C. Alzheimer’s disease: new approaches to drug discovery. Curr. Opin. Chem. Biol., 2009, 13(3), 303-308.
[http://dx.doi.org/10.1016/j.cbpa.2009.04.619] [PMID: 19467915]
[14]
Metcalfe, M.J.; Figueiredo-Pereira, M.E. Relationship between tau pathology and neuroinflammation in Alzheimer’s disease. Mt. Sinai J. Med., 2010, 77(1), 50-58.
[http://dx.doi.org/10.1002/msj.20163] [PMID: 20101714]
[15]
Carpenter, B.D.; Balsis, S.; Otilingam, P.G.; Hanson, P.K.; Gatz, M. The Alzheimer’s Disease Knowledge Scale: development and psychometric properties. Gerontologist, 2009, 49(2), 236-247.
[http://dx.doi.org/10.1093/geront/gnp023] [PMID: 19363018]
[16]
Barranco-Quintana, J.L.; Allam, M.F.; Del Castillo, A.; Navajas, R.F.C. Alzheimer’s disease risk factors. Rev. Neurol., 2005, 40(10), 613-618.
[PMID: 15926136]
[17]
Moreira, P.I.; Zhu, X.; Liu, Q.; Honda, K.; Siedlak, S.L.; Harris, P.L.; Smith, M.A.; Perry, G. Compensatory responses induced by oxidative stress in Alzheimer disease. Biol. Res., 2006, 39(1), 7-13.
[http://dx.doi.org/10.4067/S0716-97602006000100002] [PMID: 16629160]
[18]
Gong, C.X.; Lidsky, T.; Wegiel, J.; Zuck, L.; Grundke-Iqbal, I.; Iqbal, K. Phosphorylation of microtubule associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer’s disease. J. Biol. Chem., 2000, 275(8), 5535-5544.
[http://dx.doi.org/10.1074/jbc.275.8.5535] [PMID: 10681533]
[19]
Farber, S.A.; Slack, B.E.; Blusztajn, J.K. Acceleration of phosphatidylcholine synthesis and breakdown by inhibitors of mitochondrial function in neuronal cells: a model of the membrane defect of Alzheimer’s disease. FASEB J., 2000, 14(14), 2198-2206.
[http://dx.doi.org/10.1096/fj.99-0853] [PMID: 11053240]
[20]
Pohanka, M. Oxidative stress in Alzheimer disease as a target for therapy. Bratisl. Lek Listy, 2018, 119(9), 535-543.
[http://dx.doi.org/10.4149/BLL_2018_097] [PMID: 30226062]
[21]
Sonnen, J.A.; Larson, E.B.; Gray, S.L.; Wilson, A.; Kohama, S.G.; Crane, P.K.; Breitner, J.C.S.; Montine, T.J. Free radical damage to cerebral cortex in Alzheimer’s disease, microvascular brain injury, and smoking. Ann. Neurol., 2009, 65(2), 226-229.
[http://dx.doi.org/10.1002/ana.21508] [PMID: 19259965]
[22]
Oz, M.; Lorke, D.E.; Yang, K.H.S.; Petroianu, G. On the interaction of β-amyloid peptides and α7-nicotinic acetylcholine receptors in Alzheimer’s disease. Curr. Alzheimer Res., 2013, 10(6), 618-630.
[http://dx.doi.org/10.2174/15672050113109990132] [PMID: 23627750]
[23]
Suo, W.Z. Accelerating Alzheimer’s pathogenesis by GRK5 deficiency via cholinergic dysfunction. Adv. Alzheimer Dis., 2013, 02(04), 148-160.
[http://dx.doi.org/10.4236/aad.2013.24020]
[24]
Enz, A.; Amstutz, R.; Boddeke, H.; Gmelin, G.; Malanowski, J. Brain selective inhibition of acetylcholinesterase: a novel approach to therapy for Alzheimer’s disease. Prog. Brain Res., 1993, 98, 431-438.
[http://dx.doi.org/10.1016/S0079-6123(08)62429-2] [PMID: 8248533]
[25]
Whitehouse, P.J. Quality of life: the bridge from the cholinergic basal forebrain to cognitive science and bioethics. J. Alzheimers Dis., 2006, 9(Suppl. 3), 447-453.
[http://dx.doi.org/10.3233/JAD-2006-9S351] [PMID: 16914884]
[26]
Lane, R.M.; Potkin, S.G.; Enz, A. Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int. J. Neuropsychopharmacol., 2006, 9(1), 101-124.
[http://dx.doi.org/10.1017/S1461145705005833] [PMID: 16083515]
[27]
Wang, Y.; Wang, H.; Chen, H.Z. AChE inhibition-based multi-target-directed ligands, a novel pharmacological approach for the symptomatic and disease-modifying therapy of Alzheimer’s disease. Curr. Neuropharmacol., 2016, 14(4), 364-375.
[http://dx.doi.org/10.2174/1570159X14666160119094820] [PMID: 26786145]
[28]
Melchiorre, C.; Andrisano, V.; Bolognesi, M.L.; Budriesi, R.; Cavalli, A.; Cavrini, V.; Rosini, M.; Tumiatti, V.; Recanatini, M. Acetylcholinesterase noncovalent inhibitors based on a polyamine backbone for potential use against Alzheimer’s disease. J. Med. Chem., 1998, 41(22), 4186-4189.
[http://dx.doi.org/10.1021/jm9810452] [PMID: 9784091]
[29]
Karran, E.; Mercken, M.; De Strooper, B. The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat. Rev. Drug Discov., 2011, 10(9), 698-712.
[http://dx.doi.org/10.1038/nrd3505] [PMID: 21852788]
[30]
Ahmad, W.; Ijaz, B.; Shabbiri, K.; Ahmed, F.; Rehman, S. Oxidative toxicity in diabetes and Alzheimer’s disease: mechanisms behind ROS/ RNS generation. J. Biomed. Sci., 2017, 24(1), 76.
[http://dx.doi.org/10.1186/s12929-017-0379-z] [PMID: 28927401]
[31]
Bush, A.I. The metal theory of Alzheimer’s disease. J. Alzheimers Dis., 2013, 33(Suppl. 1), S277-S281.
[http://dx.doi.org/10.3233/JAD-2012-129011] [PMID: 22635102]
[32]
Shamloo, A.; Asadbegi, M.; Khandan, V.; Amanzadi, A. Designing a new multifunctional peptide for metal chelation and Aβ inhibition. Arch. Biochem. Biophys., 2018, 653, 1-9.
[http://dx.doi.org/10.1016/j.abb.2018.06.004] [PMID: 29906409]
[33]
Pudlo, M.; Luzet, V.; Ismaïli, L.; Tomassoli, I.; Iutzeler, A.; Refouvelet, B. Quinolone-benzylpiperidine derivatives as novel acetylcholinesterase inhibitor and antioxidant hybrids for Alzheimer disease. Bioorg. Med. Chem., 2014, 22(8), 2496-2507.
[http://dx.doi.org/10.1016/j.bmc.2014.02.046] [PMID: 24657052]
[34]
Luo, Z.; Sheng, J.; Sun, Y.; Lu, C.; Yan, J.; Liu, A.; Luo, H.B.; Huang, L.; Li, X. Synthesis and evaluation of multi-target-directed ligands against Alzheimer’s disease based on the fusion of donepezil and ebselen. J. Med. Chem., 2013, 56(22), 9089-9099.
[http://dx.doi.org/10.1021/jm401047q] [PMID: 24160297]
[35]
Ono, K.; Hasegawa, K.; Naiki, H.; Yamada, M. Curcumin has potent anti-amyloidogenic effects for Alzheimer’s beta-amyloid fibrils in vitro. J. Neurosci. Res., 2004, 75(6), 742-750.
[http://dx.doi.org/10.1002/jnr.20025] [PMID: 14994335]
[36]
Meena, P.; Nemaysh, V.; Khatri, M.; Manral, A.; Luthra, P.M.; Tiwari, M. Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer’s disease. Bioorg. Med. Chem., 2015, 23(5), 1135-1148.
[http://dx.doi.org/10.1016/j.bmc.2014.12.057] [PMID: 25624107]
[37]
Huang, L.; Miao, H.; Sun, Y.; Meng, F.; Li, X. Discovery of indanone derivatives as multi-target-directed ligands against Alzheimer’s disease. Eur. J. Med. Chem., 2014, 87, 429-439.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.081] [PMID: 25282266]
[38]
Najafi, Z.; Mahdavi, M.; Saeedi, M.; Karimpour-Razkenari, E.; Asatouri, R.; Vafadarnejad, F.; Moghadam, F.H.; Khanavi, M.; Sharifzadeh, M.; Akbarzadeh, T. Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors. Eur. J. Med. Chem., 2017, 125, 1200-1212.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.008] [PMID: 27863370]
[39]
Najafi, Z.; Mahdavi, M.; Saeedi, M.; Karimpour-Razkenari, E.; Edraki, N.; Sharifzadeh, M.; Khanavi, M.; Akbarzadeh, T. Novel tacrine-coumarin hybrids linked to 1,2,3-triazole as anti-Alzheimer’s compounds: In vitro and in vivo biological evaluation and docking study. Bioorg. Chem., 2019, 83, 303-316.
[http://dx.doi.org/10.1016/j.bioorg.2018.10.056] [PMID: 30396115]
[40]
Chierrito, T.P.C.; Pedersoli-Mantoani, S.; Roca, C.; Requena, C.; Sebastian-Perez, V.; Castillo, W.O.; Moreira, N.C.S.; Pérez, C.; Sakamoto-Hojo, E.T.; Takahashi, C.S.; Jiménez-Barbero, J.; Cañada, F.J.; Campillo, N.E.; Martinez, A.; Carvalho, I. From dual binding site acetylcholinesterase inhibitors to allosteric modulators: A new avenue for disease-modifying drugs in Alzheimer’s disease. Eur. J. Med. Chem., 2017, 139, 773-791.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.051] [PMID: 28863358]
[41]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science, 2002, 297(5580), 353-356.
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[42]
Tang, B.L.; Liou, Y.C. Novel modulators of amyloid-beta precursor protein processing. J. Neurochem., 2007, 100(2), 314-323.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04215.x] [PMID: 17241154]
[43]
Yahiaoui, S.; Hamidouche, K.; Ballandonne, C.; Davis, A.; de Oliveira Santos, J.S.; Freret, T.; Boulouard, M.; Rochais, C.; Dallemagne, P. Design, synthesis, and pharmacological evaluation of multitarget-directed ligands with both serotonergic subtype 4 receptor (5-HT4R) partial agonist and 5-HT6R antagonist activities, as potential treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2016, 121, 283-293.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.048] [PMID: 27266998]
[44]
Sarajärvi, T.; Jäntti, M.; Paldanius, K.M.A.; Natunen, T.; Wu, J.C.; Mäkinen, P.; Tarvainen, I.; Tuominen, R.K.; Talman, V.; Hiltunen, M. Protein kinase C -activating isophthalate derivatives mitigate Alzheimer’s disease-related cellular alterations. Neuropharmacology, 2018, 141, 76-88.
[http://dx.doi.org/10.1016/j.neuropharm.2018.08.020] [PMID: 30138694]
[45]
Cacciatore, I.; Marinelli, L.; Fornasari, E.; Cerasa, L.S.; Eusepi, P.; Türkez, H.; Pomilio, C.; Reale, M.; D’Angelo, C.; Costantini, E.; Di Stefano, A. Novel NSAID-derived drugs for the potential treatment of Alzheimer’s disease. Int. J. Mol. Sci., 2016, 17(7) E1035
[http://dx.doi.org/10.3390/ijms17071035] [PMID: 27376271]
[46]
Flagmeier, P.; Meisl, G.; Vendruscolo, M.; Knowles, T.P.J.; Dobson, C.M.; Buell, A.K.; Galvagnion, C. Mutations associated with familial Parkinson’s disease alter the initiation and amplification steps of α-synuclein aggregation. Proc. Natl. Acad. Sci. USA, 2016, 113(37), 10328-10333.
[http://dx.doi.org/10.1073/pnas.1604645113] [PMID: 27573854]
[47]
Rolli-Derkinderen, M.; Leclair-Visonneau, L.; Bourreille, A.; Coron, E.; Neunlist, M.; Derkinderen, P. Is Parkinson’s disease a chronic low-grade inflammatory bowel disease? J. Neurol., 2019.
[http://dx.doi.org/10.1007/s00415-019-09321-0] [PMID: 30989372]
[48]
Pozo Devoto, V.M.; Falzone, T.L. Mitochondrial dynamics in Parkinson’s disease: a role for α-synuclein? Dis. Model. Mech., 2017, 10(9), 1075-1087.
[http://dx.doi.org/10.1242/dmm.026294] [PMID: 28883016]
[49]
Guzior, N.; Wieckowska, A.; Panek, D.; Malawska, B. Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer’s disease. Curr. Med. Chem., 2015, 22(3), 373-404.
[http://dx.doi.org/10.2174/0929867321666141106122628] [PMID: 25386820]
[50]
Haddad, D.; Nakamura, K. Understanding the susceptibility of dopamine neurons to mitochondrial stressors in Parkinson’s disease. FEBS Lett., 2015, 589(24 Pt A), 3702-3713.
[http://dx.doi.org/10.1016/j.febslet.2015.10.021] [PMID: 26526613]
[51]
Faust, K.; Gehrke, S.; Yang, Y.; Yang, L.; Beal, M.F.; Lu, B. Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a Drosophila model of Parkinson’s disease. BMC Neurosci., 2009, 10, 109.
[http://dx.doi.org/10.1186/1471-2202-10-109] [PMID: 19723328]
[52]
Long-Smith, C.M.; Sullivan, A.M.; Nolan, Y.M. The influence of microglia on the pathogenesis of Parkinson’s disease. Prog. Neurobiol., 2009, 89(3), 277-287.
[http://dx.doi.org/10.1016/j.pneurobio.2009.08.001] [PMID: 19686799]
[53]
Ferré, S.; Popoli, P.; Giménez-Llort, L.; Rimondini, R.; Müller, C.E.; Strömberg, I.; Ögren, S.O.; Fuxe, K. Adenosine/dopamine interaction: implications for the treatment of Parkinson’s disease. Parkinsonism Relat. Disord., 2001, 7(3), 235-241.
[http://dx.doi.org/10.1016/S1353-8020(00)00063-8] [PMID: 11331192]
[54]
Morelli, M.; Di Paolo, T.; Wardas, J.; Calon, F.; Xiao, D.; Schwarzschild, M.A. Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications. Prog. Neurobiol., 2007, 83(5), 293-309.
[http://dx.doi.org/10.1016/j.pneurobio.2007.07.001] [PMID: 17826884]
[55]
Jenner, P.; Mori, A.; Hauser, R.; Morelli, M.; Fredholm, B.B.; Chen, J.F. Adenosine, adenosine A 2A antagonists, and Parkinson’s disease. Parkinsonism Relat. Disord., 2009, 15(6), 406-413.
[http://dx.doi.org/10.1016/j.parkreldis.2008.12.006] [PMID: 19446490]
[56]
Petzer, J.P.; Castagnoli, N., Jr.; Schwarzschild, M.A.; Chen, J.F.; Van der Schyf, C.J. Dual-target-directed drugs that block monoamine oxidase B and adenosine A(2A) receptors for Parkinson’s disease. Neurotherapeutics, 2009, 6(1), 141-151.
[http://dx.doi.org/10.1016/j.nurt.2008.10.035] [PMID: 19110205]
[57]
Fišar, Z. Drugs related to monoamine oxidase activity. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2016, 69, 112-124.
[http://dx.doi.org/10.1016/j.pnpbp.2016.02.012] [PMID: 26944656]
[58]
Chen, J.F.; Steyn, S.; Staal, R.; Petzer, J.P.; Xu, K.; Van Der Schyf, C.J.; Castagnoli, K.; Sonsalla, P.K.; Castagnoli, N., Jr; Schwarzschild, M.A. 8-(3-Chlorostyryl)caffeine may attenuate MPTP neurotoxicity through dual actions of monoamine oxidase inhibition and A2A receptor antagonism. J. Biol. Chem., 2002, 277(39), 36040-36044.
[http://dx.doi.org/10.1074/jbc.M206830200] [PMID: 12130655]
[59]
Pretorius, J.; Malan, S.F.; Castagnoli, N., Jr; Bergh, J.J.; Petzer, J.P. Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues. Bioorg. Med. Chem., 2008, 16(18), 8676-8684.
[http://dx.doi.org/10.1016/j.bmc.2008.07.088] [PMID: 18723354]
[60]
Stössel, A.; Schlenk, M.; Hinz, S.; Küppers, P.; Heer, J.; Gütschow, M.; Müller, C.E. Dual targeting of adenosine A(2A) receptors and monoamine oxidase B by 4H-3,1-benzothiazin-4-ones. J. Med. Chem., 2013, 56(11), 4580-4596.
[http://dx.doi.org/10.1021/jm400336x] [PMID: 23631427]
[61]
Robinson, S.J.; Petzer, J.P.; Terre’Blanche, G.; Petzer, A.; van der Walt, M.M.; Bergh, J.J.; Lourens, A.C. 2-Aminopyrimidines as dual adenosine A1/A2A antagonists. Eur. J. Med. Chem., 2015, 104, 177-188.
[http://dx.doi.org/10.1016/j.ejmech.2015.09.035] [PMID: 26462195]
[62]
Mori, A. Adenosine A2A receptor antagonists as a novel non-dopaminergic therapy for Parkinson’s disease: A potential mechanism of the antiparkinsonian action. J. Neurol. Sci., 2006, 248(1-2), 319-319.
[63]
Müller, W.E.; Eckert, A.; Kurz, C.; Eckert, G.P.; Leuner, K. Mitochondrial dysfunction: common final pathway in brain aging and Alzheimer’s disease--therapeutic aspects. Mol. Neurobiol., 2010, 41(2-3), 159-171.
[http://dx.doi.org/10.1007/s12035-010-8141-5] [PMID: 20461558]
[64]
Ammal Kaidery, N.; Thomas, B. Current perspective of mitochondrial biology in Parkinson’s disease. Neurochem. Int., 2018, 117, 91-113.
[http://dx.doi.org/10.1016/j.neuint.2018.03.001] [PMID: 29550604]
[65]
Biju, K.C.; Evans, R.C.; Shrestha, K.; Carlisle, D.C.B.; Gelfond, J.; Clark, R.A. Methylene blue ameliorates olfactory dysfunction and motor deficits in a chronic MPTP/probenecid mouse model of Parkinson’s disease. Neuroscience, 2018, 380, 111-122.
[http://dx.doi.org/10.1016/j.neuroscience.2018.04.008] [PMID: 29684508]
[66]
Zaitone, S.A.; Abo-Elmatty, D.M.; Elshazly, S.M. Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats. Indian J. Pharmacol., 2012, 44(6), 774-779.
[http://dx.doi.org/10.4103/0253-7613.103300] [PMID: 23248410]
[67]
Tan, W.; Xue-bin, C.; Tian, Z.; Xiao-wu, C.; Pei-pei, H.; Zhi-bin, C.; Bei-sha, T. Effects of simvastatin on the expression of inducible nitric oxide synthase and brain-derived neurotrophic factor in a lipopolysaccharide-induced rat model of Parkinson disease. Int. J. Neurosci., 2016, 126(3), 278-286.
[http://dx.doi.org/10.3109/00207454.2015.1012758] [PMID: 26000813]
[68]
Kuang, S.; Yang, L.; Rao, Z.; Zhong, Z.; Li, J.; Zhong, H.; Dai, L.; Tang, X. Effects of ginkgo biloba extract on A53T alpha-synuclein transgenic mouse models of Parkinson’s disease. Can. J. Neurol. Sci., 2018, 45(2), 182-187.
[http://dx.doi.org/10.1017/cjn.2017.268] [PMID: 29506601]
[69]
Shirooie, S.; Nabavi, S.F.; Dehpour, A.R.; Belwal, T.; Habtemariam, S.; Argüelles, S.; Sureda, A.; Daglia, M.; Tomczyk, M.; Sobarzo-Sanchez, E.; Xu, S.; Nabavi, S.M. Targeting mTORs by omega-3 fatty acids: A possible novel therapeutic strategy for neurodegeneration? Pharmacol. Res., 2018, 135, 37-48.
[http://dx.doi.org/10.1016/j.phrs.2018.07.004] [PMID: 29990625]
[70]
Yong-Kee, C.J.; Sidorova, E.; Hanif, A.; Perera, G.; Nash, J.E. Mitochondrial dysfunction precedes other sub-cellular abnormalities in an in vitro model linked with cell death in Parkinson’s disease. Neurotox. Res., 2012, 21(2), 185-194.
[http://dx.doi.org/10.1007/s12640-011-9259-6] [PMID: 21773851]
[71]
Almeida, A.S.; Vieira, H.L.A. Role of cell metabolism and mitochondrial function during adult neurogenesis. Neurochem. Res., 2017, 42(6), 1787-1794.
[http://dx.doi.org/10.1007/s11064-016-2150-3] [PMID: 28000162]
[72]
Giedt, R.J.; Pfeiffer, D.R.; Matzavinos, A.; Kao, C.Y.; Alevriadou, B.R. Mitochondrial dynamics and motility inside living vascular endothelial cells: role of bioenergetics. Ann. Biomed. Eng., 2012, 40(9), 1903-1916.
[http://dx.doi.org/10.1007/s10439-012-0568-6] [PMID: 22527011]
[73]
Golpich, M.; Amini, E.; Mohamed, Z.; Azman Ali, R.; Mohamed Ibrahim, N.; Ahmadiani, A. Mitochondrial dysfunction and biogenesis in neurodegenerative diseases: pathogenesis and treatment. CNS Neurosci. Ther., 2017, 23(1), 5-22.
[http://dx.doi.org/10.1111/cns.12655] [PMID: 27873462]
[74]
Umeno, A.; Biju, V.; Yoshida, Y. In vivo ROS production and use of oxidative stress-derived biomarkers to detect the onset of diseases such as Alzheimer’s disease, Parkinson’s disease and diabetes. Free Radic. Res., 2017, 51(4), 413-427.
[http://dx.doi.org/10.1080/10715762.2017.1315114] [PMID: 28372523]
[75]
Yue, P.; Gao, L.; Wang, X.; Ding, X.; Teng, J. Pretreatment of glial cell-derived neurotrophic factor and geranylgeranylacetone ameliorates brain injury in Parkinson’s disease by its anti-apoptotic and anti-oxidative property. J. Cell. Biochem., 2018, 119(7), 5491-5502.
[http://dx.doi.org/10.1002/jcb.26712] [PMID: 29377238]
[76]
Nomura, D.K.; Dix, M.M.; Cravatt, B.F. Activity-based protein profiling for biochemical pathway discovery in cancer. Nat. Rev. Cancer, 2010, 10(9), 630-638.
[http://dx.doi.org/10.1038/nrc2901] [PMID: 20703252]
[77]
Gou, Y.; Zhang, Z.; Li, D.; Zhao, L.; Cai, M.; Sun, Z.; Li, Y.; Zhang, Y.; Khan, H.; Sun, H.; Wang, T.; Liang, H.; Yang, F. HSA-based multi-target combination therapy: regulating drugs’ release from HSA and overcoming single drug resistance in a breast cancer model. Drug Deliv., 2018, 25(1), 321-329.
[http://dx.doi.org/10.1080/10717544.2018.1428245] [PMID: 29350051]
[78]
Jin, H.; Dan, H.G.; Rao, G.W. Research progress in quinazoline derivatives as multi-target tyrosine kinase inhibitors. Heterocycl. Commun., 2018, 24(1), 1-10.
[http://dx.doi.org/10.1515/hc-2017-0066]
[79]
Gossage, L.; Eisen, T. Targeting multiple kinase pathways: a change in paradigm. Clin. Cancer Res., 2010, 16(7), 1973-1978.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-3182] [PMID: 20215532]
[80]
Kranenburg, O.; Emmink, B.L.; Knol, J.; van Houdt, W.J.; Rinkes, I.H.M.B.; Jimenez, C.R. Proteomics in studying cancer stem cell biology. Expert Rev. Proteomics, 2012, 9(3), 325-336.
[http://dx.doi.org/10.1586/epr.12.24] [PMID: 22809210]
[81]
Raevsky, O.A.; Mukhametov, A.; Grigorev, V.Y.; Ustyugov, A.; Tsay, S.C.; Jih-Ru Hwu, R.; Yarla, N.S.; Tarasov, V.V.; Aliev, G.; Bachurin, S.O. Applications of multi-target computer-aided methodologies in molecular design of CNS drugs. Curr. Med. Chem., 2018, 25(39), 5293-5314.
[http://dx.doi.org/10.2174/0929867324666170920154111] [PMID: 28933295]
[82]
Okura, R.; Yoshioka, H.; Yoshioka, M.; Hiromasa, K.; Nishio, D.; Nakamura, M. Expression of AID in malignant melanoma with BRAF(V600E) mutation. Exp. Dermatol., 2014, 23(5), 347-348.
[http://dx.doi.org/10.1111/exd.12402] [PMID: 24684646]
[83]
Poulikakos, P.I.; Zhang, C.; Bollag, G.; Shokat, K.M.; Rosen, N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature, 2010, 464(7287), 427-430.
[http://dx.doi.org/10.1038/nature08902] [PMID: 20179705]
[84]
Wada, M.; Horinaka, M.; Yamazaki, T.; Katoh, N.; Sakai, T. The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells. PLoS One, 2014, 9(11) e113217
[http://dx.doi.org/10.1371/journal.pone.0113217] [PMID: 25422890]
[85]
Den, R.B.; Lu, B. Heat shock protein 90 inhibition: rationale and clinical potential. Ther. Adv. Med. Oncol., 2012, 4(4), 211-218.
[http://dx.doi.org/10.1177/1758834012445574] [PMID: 22754594]
[86]
Rasouliha, B.H.; Zhou, Y.S.; Chen, W.N. iTRAQ-coupled 2D LC-MS/MS analysis of protein profile in MCF-7 human breast cancer cells incubated with doxorubicin: Potential role of heat shock protein 90. J. Med. Imag. Health. In., 2011, 1(2), 193-195.
[http://dx.doi.org/10.1166/jmihi.2011.1026]
[87]
Moulick, K.; Ahn, J.H.; Zong, H.; Rodina, A.; Cerchietti, L.; Gomes DaGama, E.M.; Caldas-Lopes, E.; Beebe, K.; Perna, F.; Hatzi, K.; Vu, L.P.; Zhao, X.; Zatorska, D.; Taldone, T.; Smith-Jones, P.; Alpaugh, M.; Gross, S.S.; Pillarsetty, N.; Ku, T.; Lewis, J.S.; Larson, S.M.; Levine, R.; Erdjument-Bromage, H.; Guzman, M.L.; Nimer, S.D.; Melnick, A.; Neckers, L.; Chiosis, G. Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90. Nat. Chem. Biol., 2011, 7(11), 818-826.
[http://dx.doi.org/10.1038/nchembio.670] [PMID: 21946277]
[88]
Zhang, Q.; Zhai, S.; Li, L.; Li, X.; Zhou, H.; Liu, A.; Su, G.; Mu, Q.; Du, Y.; Yan, B. Anti-tumor selectivity of a novel tubulin and HSP90 dual-targeting inhibitor in non-small cell lung cancer models. Biochem. Pharmacol., 2013, 86(3), 351-360.
[http://dx.doi.org/10.1016/j.bcp.2013.05.019] [PMID: 23743233]
[89]
Detmar, M. Tumor angiogenesis. J. Investig. Dermatol. Symp. Proc., 2000, 5(1), 20-23.
[http://dx.doi.org/10.1046/j.1087-0024.2000.00003.x] [PMID: 11147670]
[90]
Di Cesare, E.; Verrico, A.; Miele, A.; Giubettini, M.; Rovella, P.; Coluccia, A.; Famiglini, V.; La Regina, G.; Cundari, E.; Silvestri, R.; Lavia, P. Mitotic cell death induction by targeting the mitotic spindle with tubulin-inhibitory indole derivative molecules. Oncotarget, 2017, 8(12), 19738-19759.
[http://dx.doi.org/10.18632/oncotarget.14980] [PMID: 28160569]
[91]
Chekler, E.L.P.; Kiselyov, A.S.; Ouyang, X.; Chen, X.; Pattaropong, V.; Wang, Y.; Tuma, M.C.; Doody, J.F. Discovery of dual VEGFR-2 and tubulin inhibitors with in vivo efficacy. ACS Med. Chem. Lett., 2010, 1(9), 488-492.
[http://dx.doi.org/10.1021/ml1001568] [PMID: 24900236]
[92]
Li, X.; Wu, C.; Lin, X.; Cai, X.; Liu, L.; Luo, G.; You, Q.; Xiang, H. Synthesis and biological evaluation of 3-aryl-quinolin derivatives as anti-breast cancer agents targeting ERα and VEGFR-2. Eur. J. Med. Chem., 2019, 161, 445-455.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.045] [PMID: 30384047]
[93]
Campo, L.; Mathew, M.; Breuer, E.K.; Small, W. The role of TACC3 in the progression from ductal carcinoma in situ to invasive breast cancer. Cancer Res., 2017, 77.
[http://dx.doi.org/10.1158/1538-7445.AM2017-3019]
[94]
de Oliveira Viana, J.; Ishiki, H.M.; Scotti, M.T.; Scotti, L. Multi-target antitubercular drugs. Curr. Top. Med. Chem., 2018, 18(9), 750-758.
[http://dx.doi.org/10.2174/1568026618666180528124414] [PMID: 29807515]
[95]
Ghazaei, C. Mycobacterium tuberculosis and lipids: Insights into molecular mechanisms from persistence to virulence. J. Res. Med. Sci., 2018, 23, 63.
[http://dx.doi.org/10.4103/jrms.JRMS_904_17] [PMID: 30181745]
[96]
Saravanan, P.; Patra, S. Discovery of potential dual inhibitors against lipases Rv0183 and Rv3802c for tuberculosis therapeutics. Lett. Drug Des. Discov., 2016, 13(2), 185-195.
[http://dx.doi.org/10.2174/1570180812999150812165215]
[97]
Watts, C. Neglected tropical diseases: a DFID perspective. Plos. Neglect. Trop. D, 2017, 11(4) e0005492.
[http://dx.doi.org/10.1371/journal.pntd.0005492] [PMID: 28426666]
[98]
Molyneux, D.H. Neglected tropical diseases: now more than just ‘other diseases’--the post-2015 agenda. Int. Health, 2014, 6(3), 172-180.
[http://dx.doi.org/10.1093/inthealth/ihu037] [PMID: 24969646]
[99]
Coelho, G.S.; Andrade, J.S.; Xavier, V.F.; Sales Junior, P.A.; Rodrigues de Araujo, B.C.; Fonseca, K.D.S.; Caetano, M.S.; Murta, S.M.F.; Vieira, P.M.; Carneiro, C.M.; Taylor, J.G. Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi. Chem. Biol. Drug Des., 2019, 93(3), 337-350.
[http://dx.doi.org/10.1111/cbdd.13420] [PMID: 30362274]
[100]
Aguilera, E.; Varela, J.; Birriel, E.; Serna, E.; Torres, S.; Yaluff, G.; de Bilbao, N.V.; Aguirre-López, B.; Cabrera, N.; Díaz Mazariegos, S.; de Gómez-Puyou, M.T.; Gómez-Puyou, A.; Pérez-Montfort, R.; Minini, L.; Merlino, A.; Cerecetto, H.; González, M.; Alvarez, G. Potent and selective inhibitors of trypanosoma cruzi triosephosphate isomerase with concomitant inhibition of cruzipain: inhibition of parasite growth through multitarget activity. Chem. Med. Chem., 2016, 11(12), 1328-1338.
[http://dx.doi.org/10.1002/cmdc.201500385] [PMID: 26492824]
[101]
Belluti, F.; Uliassi, E.; Veronesi, G.; Bergamini, C.; Kaiser, M.; Brun, R.; Viola, A.; Fato, R.; Michels, P.A.M.; Krauth-Siegel, R.L.; Cavalli, A.; Bolognesi, M.L. Toward the development of dual-targeted glyceraldehyde-3-phosphate dehydrogenase/trypanothione reductase inhibitors against Trypanosoma brucei and Trypanosoma cruzi. ChemMedChem, 2014, 9(2), 371-382.
[http://dx.doi.org/10.1002/cmdc.201300399] [PMID: 24403089]
[102]
Stolp, Z.D.; Smurthwaite, C.A.; Reed, C.; Williams, W.; Dharmawan, A.; Djaballah, H.; Wolkowicz, R. A multiplexed cell-based assay for the identification of modulators of pre-membrane processing as a target against dengue virus. J. Biomol. Screen., 2015, 20(5), 616-626.
[http://dx.doi.org/10.1177/1087057115571247] [PMID: 25724189]
[103]
Sankarasubramanian, J.; Pavithra, K.B.; Kavitha, B. Identification of potent inhibitor for RNA dependent RNA polymerase (RDRP) of dengue virus serotype-3: A molecular docking study. J. Appl. Bioinforma. Comput. Biol., 2015, 04(01)
[http://dx.doi.org/10.4172/2329-9533.1000113]
[104]
Mustafa, M.S.; Rasotgi, V.; Jain, S.; Gupta, V. Discovery of fifth serotype of dengue virus (DENV-5): A new public health dilemma in dengue control. Med. J. Armed Forces India, 2015, 71(1), 67-70.
[http://dx.doi.org/10.1016/j.mjafi.2014.09.011] [PMID: 25609867]
[105]
Qamar, M.T.U.; Arooj, M.; Rabbia, N.; Amna, A.; Tabeer, F.; Tehreem, J.; Zubair, A.; Usman Ali, A.J.B. Molecular docking based screening of plant flavonoids as Dengue NS1 inhibitors. Bioinformation, 2014, 10(7), 460-465.
[http://dx.doi.org/10.6026/97320630010460] [PMID: 25187688]
[106]
Senthilvel, P.; Lavanya, P.; Kumar, K.M.; Swetha, R.; Anitha, P.; Bag, S.; Sarveswari, S.; Vijayakumar, V.; Ramaiah, S.; Anbarasu, A. Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly. Bioinformation, 2013, 9(18), 889-895.
[http://dx.doi.org/10.6026/97320630009889] [PMID: 24307765]
[107]
de Sousa, L.R.F.; Wu, H.; Nebo, L.; Fernandes, J.B.; da Silva, M.F.D.F.; Kiefer, W.; Kanitz, M.; Bodem, J.; Diederich, W.E.; Schirmeister, T.; Vieira, P.C. Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: inhibition kinetics and docking studies. Bioorg. Med. Chem., 2015, 23(3), 466-470.
[http://dx.doi.org/10.1016/j.bmc.2014.12.015] [PMID: 25564380]
[108]
Ye, H.; Ye, L.; Kang, H.; Zhang, D.; Tao, L.; Tang, K.; Liu, X.; Zhu, R.; Liu, Q.; Chen, Y.Z.; Li, Y.; Cao, Z. HIT: linking herbal active ingredients to targets. Nucleic Acids Res., 2011, 39(Database issue), D1055-D1059.
[http://dx.doi.org/10.1093/nar/gkq1165] [PMID: 21097881]

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