4,184
Views
65
CrossRef citations to date
0
Altmetric
Editorial

The use of multi-target drugs in the treatment of neurodegenerative diseases

Pages 293-298 | Published online: 10 Jan 2014

References

  • Burgut FT, Benaur M, Hencliffe C. Late-life depression: a neuropsychiatric approach. Expert Rev. Neurother.6(1), 65–72 (2006).
  • Cummings JL, Zhong K. Treatments for behavioural disorders in neurodegenerative diseases: drug development strategies. Nat. Rev. Drug Discov.5(1), 64–74 (2006).
  • Jellinger KA. Basic mechanisms of neurodegeneration: a critical update. J. Cell. Mol. Med.14(3), 457–487 (2010).
  • Cavallucci V, D’Amelio M. Matter of life and death: the pharmacological approaches targeting apoptosis in brain diseases. Curr. Pharm. Des.17(3), 215–229 (2011).
  • Lang AE. Clinical trials of disease-modifying therapies for neurodegenerative diseases: the challenges and the future. Nat. Med.16(11), 1223–1226 (2010).
  • Ferreira IL, Resende R, Ferreiro E et al. Multiple defects in energy metabolism in Alzheimer’s disease. Curr. Drug Targets11(10), 1193–1206 (2010).
  • Piau A, Nourhashémi F, Hein C et al. Progress in the development of new drugs in Alzheimer’s disease. J. Nutr. Health Aging15(1), 45–57 (2011).
  • Van der Schyf CJ, Youdim MB. Multifunctional drugs as neurotherapeutics. Neurotherapeutics6(1), 1–3 (2009).
  • Pruss RM. Phenotypic screening strategies for neurodegenerative diseases: a pathway to discover novel drug candidates and potential disease targets or mechanisms. CNS Neurol. Disord. Drug Targets9(6), 693–700 (2010).
  • Levy OA, Malagelada C, Greene LA. Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Apoptosis14(4), 478–500 (2009).
  • Bar-Am O, Amit T, Weinreb O et al. Propargylamine containing compounds as modulators of proteolytic cleavage of amyloid-β protein precursor: involvement of MAPK and PKC activation. J. Alzheimers Dis.21(2), 361–371 (2010).
  • Van der Schyf CJ, Geldenhuys WJ, Youdim MB. Multifunctional drugs with different CNS targets for neuropsychiatric disorders. J. Neurochem.99(4), 1033–1048 (2006).
  • Chertkow Y, Weinreb O, Youdim MB et al. Molecular mechanisms underlying synergistic effects of SSRI-antipsychotic augmentation in treatment of negative symptoms in schizophrenia. J. Neural Transm.116(11), 1529–1541 (2009).
  • Rutherford GW, Sangani PR, Kennedy GE. Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection. Cochrane Database Syst. Rev.4, CD002037 (2003).
  • Chung KF, Adcock IM. Combination therapy of long-acting β2-adrenoceptor agonists and corticosteroids for asthma. Treat. Respir. Med.3(5), 279–289 (2004).
  • Frishman WH, Zuckerman AL. Amlodipine/atorvastatin: the first cross risk factor polypill for the prevention and treatment of cardiovascular disease. Expert Rev. Cardiovasc. Ther.2(5), 675–681 (2004).
  • Zerkak D, Dougados M. Benefit/risk of combination therapies. Clin. Exp. Rheumatol.22(5 Suppl. 35), S71–S76 (2004).
  • Keith CT, Borisy AA, Stockwell BR. Multicomponent therapeutics for networked systems. Nat. Rev. Drug Discov.4(1), 71–78 (2005).
  • Smid P, Coolen HK, Keizer HG et al. Synthesis, structure-activity relationships, and biological properties of 1-heteroaryl-4-[ω-(1H-indol-3-yl)alkyl]piperazines, novel potential antipsychotics combining potent dopamine D2 receptor antagonism with potent serotonin reuptake inhibition. J. Med. Chem.48(22), 6855–6869 (2005).
  • Schmitt B, Bernhardt T, Moeller HJ et al. Combination therapy in Alzheimer’s disease: a review of current evidence. CNS Drugs18(13), 827–844 (2004).
  • Holmes HM, Sachs GA, Shega JW et al. Integrating palliative medicine into the care of persons with advanced dementia: identifying appropriate medication use. J. Am. Geriatr. Soc.56(7), 1306–1311 (2008).
  • Morphy R, Rankovic Z. Designed multiple ligands. An emerging drug discovery paradigm. J. Med. Chem.48(21), 6523–6543 (2005).
  • Morphy R, Rankovic Z. Designing multiple ligands – medicinal chemistry strategies and challenges. Curr. Pharm. Des.15(6), 587–600 (2009).
  • Stahl SM. Multifunctional drugs: a novel concept for psychopharmacology. CNS Spectr.14(2), 71–73 (2009).
  • Youdim MB, Van der Schyf CJ. Magic bullets or novel multimodal drugs with various targets for Parkinson’s disease? Nat. Rev. Drug Discov.6(6), iii–vi (2007).
  • Bolognesi ML, Matera R, Minarini A et al. Alzheimer’s disease: new approaches to drug discovery. Curr. Opin. Chem. Biol.13(3), 303–308 (2009).
  • Bolognesi ML, Rosini M, Andrisano V. MTDL design strategy in the context of Alzheimer’s disease: from lipocrine to memoquin and beyond. Curr. Pharm. Des.15(6), 601–613 (2009).
  • Durrant JD, Amaro RE, Xie L et al. A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology. PLoS Comput. Biol.6(1), e1000648 (2010).
  • Schrattenholz A, Groebe K, Soskic V. Systems biology approaches and tools for analysis of interactomes and multi-target drugs. Methods Mol. Biol.662, 29–58 (2010).
  • Tsuji S. Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum. Mol. Genet.19(R1), R65–R70 (2010).
  • Bolognesi ML, Banzi R, Bartolini M et al. Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer’s disease. J. Med. Chem.50(20), 4882–4897 (2007).
  • Bolognesi ML, Cavalli A, Melchiorre C. Memoquin: a multi-target-directed ligand as an innovative therapeutic opportunity for Alzheimer’s disease. Neurotherapeutics6(1), 152162 (2009).
  • Bolognesi ML, Bartolini M, Rosini M et al. Structure–activity relationships of memoquin: influence of the chain chirality in the multi-target mechanism of action. Bioorg. Med. Chem. Lett.19(15), 4312–4315 (2009).
  • Bolognesi ML, Cavalli A, Bergamini C et al. Toward a rational design of multitarget-directed antioxidants: merging memoquin and lipoic acid molecular frameworks. J. Med. Chem.52(23), 7883–7886 (2009).
  • Bolognesi ML, Bartolini M, Tarozzi A. Multitargeted drugs discovery: balancing anti-amyloid and anticholinesterase capacity in a single chemical entity. Bioorg. Med. Chem. Lett. DOI: 10.1016/j.bmcl.2010.12.093 (2010) (Epub ahead of print).
  • Weinstock M, Bejar C, Wang RH et al. TV3326, a novel neuroprotective drug with cholinesterase and monoamine oxidase inhibitory activities for the treatment of Alzheimer’s disease. J. Neural. Transm. Suppl.60, 157–169 (2000).
  • Weinreb O, Amit T, Bar-Am O et al. The neuroprotective mechanism of action of the multimodal drug ladostigil. Front. Biosci.13, 5131–5137 (2008).
  • Sagi Y, Weinstock M, Youdim MB. Attenuation of MPTP-induced dopaminergic neurotoxicity by TV3326, a cholinesterase-monoamine oxidase inhibitor. J. Neurochem.86(2), 290–297 (2003).
  • Youdim MB, Buccafusco JJ. CNS targets for multi-functional drugs in the treatment of Alzheimer’s and Parkinson’s diseases. J. Neural Transm.112(4), 519–537 (2005).
  • Magaki S, Raghavan R, Mueller C et al. Iron, copper, and iron regulatory protein 2 in Alzheimer’s disease and related dementias. Neurosci. Lett.418(1), 72–76 (2007).
  • Zheng H, Weiner LM, Bar-Am O et al. Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. Bioorg. Med. Chem.13(3), 773–783 (2005).
  • Youdim MB, Stephenson G, Ben Shachar D. Ironing iron out in Parkinson’s disease and other neurodegenerative diseases with iron chelators: a lesson from 6-hydroxydopamine and iron chelators, desferal and VK-28. Ann. NY Acad. Sci.1012, 306–325 (2004).
  • Van der Schyf CJ, Gal S, Geldenhuys WJ et al. Multifunctional neuroprotective drugs targeting monoamine oxidase inhibition, iron chelation, adenosine receptors, and cholinergic and glutamatergic action for neurodegenerative diseases. Expert Opin. Investig. Drugs.15(8), 873–886 (2006).
  • Chimenti F, Bolasco A, Manna F et al. Synthesis, biological evaluation and 3D-QSAR of 1,3,5-trisubstituted-4,5-dihydro-(1H)-pyrazole derivatives as potent and highly selective monoamine oxidase A inhibitors. Curr. Med. Chem.13(12), 1411–1428 (2006).
  • Choi JS, Braymer JJ, Nanga RP, Ramamoorthy A, Lim MH. Design of small molecules that target metal-Aβ species and regulate metal-induced Aβ aggregation and neurotoxicity. Proc. Natl Acad. Sci. USA107(51), 21990–21995 (2010).
  • Mancino AM, Hindo SS, Kochi A et al. Effects of clioquinol on metal-triggered amyloid-β aggregation revisited. Inorg. Chem.48(20), 9596–9598 (2009).
  • Hindo SS, Mancino AM, Braymer JJ et al. Small molecule modulators of copper-induced Aβ aggregation. J. Am. Chem. Soc.131(46), 16663–16665 (2009).
  • Frédérick R, Ooms F, Castagnoli N Jr et al. (E)-8-(3-chlorostyryl)-1,3,7-trimethylxanthine, a caffeine derivative acting both as antagonist of adenosine A2A receptors and as inhibitor of MAO-B. Acta Crystallogr. C61(Pt 9), O531–O532 (2005).
  • Dall’Igna OP, Fett P, Gomes MW et al. Caffeine and adenosine A2A receptor antagonists prevent β-amyloid (25–35)-induced cognitive deficits in mice. Exp. Neurol.203(1), 241–245 (2007).
  • Prediger RD, Batista LC, Takahashi RN. Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats. Involvement of adenosine A1 and A2A receptors. 26(6), 957–964 (2005).
  • Petzer JP, Castagnoli N Jr, Schwarzschild MA et al. Dual-target-directed drugs that block monoamine oxidase B and adenosine A2A receptors for Parkinson’s disease. Neurotherapeutics6(1), 141–151 (2009).
  • Krieglstein J, Lippert K, Pöch G. Apparent independent action of nimodipine and glutamate antagonists to protect cultured neurons against glutamate-induced damage. Neuropharmacology35(12), 1737–1742 (1996).
  • Stuiver BT, Douma BR, Bakker R et al. In vivo protection against NMDA-induced neurodegeneration by MK-801 and nimodipine: combined therapy and temporal course of protection. Neurodegeneration5(2), 153–159 (1996).
  • Kiewert C, Hartmann J, Stoll J et al. NGP1-01 is a brain-permeable dual blocker of neuronal voltage- and ligand-operated calcium channels. Neurochem. Res.31(3), 395–399 (2006).
  • Geldenhuys WJ, Malan SF, Bloomquist JR et al. Structure-activity relationships of pentacycloundecylamines at the N-methyl-D-aspartate receptor. Bioorg. Med. Chem.15(3), 1525–1532 (2007).
  • Van der Schyf CJ, Geldenhuys WJ. Polycyclic compounds: ideal drug scaffolds for the design of multiple mechanism drugs? Neurotherapeutics6(1), 175–186 (2009).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.