Multifunctional compounds: Smart molecules for multifactorial diseases

European Journal of Medicinal Chemistry

Volumn 76, Issue , 2014, Pages 31-42

  Bansal, Yogita ^a   Silakari, Om ^a  

^a PUNJABI UNIVERSITY   (India)

Author keywords

Chimeric; Hybrid; Multifactorial; Multifunctional; Multiple ligands; Multitarget

Indexed keywords

5 [N METHYL N PROPARGYLAMINOMETHYL] 8 HYDROXYQUINOLINE; ANTIDEPRESSANT AGENT; ANTIDIABETIC AGENT; ANTIDOTE; ANTIINFLAMMATORY AGENT; ANTIMALARIAL AGENT; ANTIOXIDANT; ANTIPARKINSON AGENT; ARTEMISNIN; ATYPICAL ANTIPSYCHOTIC AGENT; BERBERINE; CURCUMIN; DONEPEZIL; DULOXETINE; HYPOCHOLESTEROLEMIC AGENT; LADOSTIGIL; LAPATINIB; LEONURINE; MONOAMINE OXIDASE B INHIBITOR; MULTIFUNCTIONAL COMPOUND; NONSTEROID ANTIINFLAMMATORY AGENT; ORGANOPHOSPHORUS COMPOUND; QUININE; RIVASTIGMINE; SUNITINIB; TACRINE; UNCLASSIFIED DRUG; ZIPRASIDONE;

ALZHEIMER DISEASE; ANTIMALARIAL ACTIVITY; ASTHMA; ATHEROSCLEROSIS; DEPRESSION; DIABETES MELLITUS; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HYBRIDIZATION; HYPERTENSION; INTOXICATION; MALARIA FALCIPARUM; METABOLIC SYNDROME X; MULTIPLE SCLEROSIS; NEOPLASM; ORGANOPHOSPHORUS POISONING; OSTEOARTHRITIS; PARKINSON DISEASE; PHARMACOPHORE; REVIEW; RHEUMATOID ARTHRITIS; SCHIZOPHRENIA; DRUG DESIGN; MEDICINAL CHEMISTRY;

CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN;

EID: 84896736436     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.01.060     Document Type: Short Survey

References (112)

1. Y. Shahin, J.A. Khan, and I. Chetter Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials Atherosclerosis 221 2012 18 33
2. M. Sata Role of chronic inflammation in the pathogenesis of atherosclerosis Nihon Yakurigaku Zasshi 138 2011 182 186
3. C. Weber, and H. Noels Atherosclerosis: current pathogenesis and therapeutic options Natural Medicines 17 2011 1410 1422
4. M.P. Lichtenstein, P. Carriba, R. Masgrau, A. Pujol, and E. Galea Staging anti-inflammatory therapy in alzheimer's disease Frontiers in Aging Neuroscience 2 2010 1 6
5. W.J. Geldenhuys, M.B.H. Youdim, R.T. Carroll, and C.J. Van der Schyf The emergence of designed multiple ligands for neurodegenerative disorders Progress in Neurobiology 94 2011 347 359
6. H.Y. Zhang One-compound-multiple-targets strategy to combat Alzheimer's disease FEBS Letters 579 2005 5260 5264
7. C.J. Van der Schyf, and W.J. Geldenhuys Multimodal drugs and their future for Alzheimer's and Parkinson's disease International Review of Neurobiology 100 2011 107 125
8. M.B.H. Youdima, W.J. Geldenhuysb, and C.J. Van der Schyf Why should we use multifunctional neuroprotective and neurorestorative drugs for Parkinson's disease? Parkinsonism & Related Disorders 13 2007 S281 S291
9. A. Gella, and N. Durany Oxidative stress in Alzheimer disease Cell Adhesion & Migration 3 2009 88 93
10. Y. Christen Oxidative stress and Alzheimer disease American Journal of Clinical Nutrition 71 2000 621S 629S (Pubitemid 30061247)
11. P. Cirillo, Y.Y. Sautin, J. Kanellis, D.-H. Kang, L. Gesualdo, T. Nakagawa, and R.J. Johnson Systemic inflammation, metabolic syndrome and progressive renal disease Nephrology Dialysis Transplantation 24 2009 1384 1387
12. I.B. McInnes, and G. Schett The pathogenesis of rheumatoid arthritis The New England Journal of Medicine 365 2011 2205 2219
13. K.F. Daoud, C.G. Jackson, and H.J. Williams Basic therapy for rheumatoid arthritis: nonsteroidal anti-inflammatory drugs Comprehensive Therapy 25 1999 427 433 (Pubitemid 29455775)
14. M.V. Volin, and A.E. Koch Interleukin-18: a mediator of inflammation and angiogenesis in rheumatoid arthritis Journal of Interferon and Cytokine Research 31 2011 745 751
15. S. Kolahian, and R. Gosens Cholinergic regulation of airway inflammation and remodelling Journal of Allergy 2012 10.1155/2012/681258 Art. No. 681258
16. A. Ozier, I. Bara, P.O. Girodet, R. Marthan, and P. Berger Pathophysiology of asthma Revue du Praticien 61 2011 339 345
17. P. Fireman Understanding asthma pathophysiology Allergy and Asthma Proceedings 24 2003 79 83 (Pubitemid 37034191)
18. M. Wang, J. Shen, H. Jin, H.J. Im, J. Sandy, and D. Chen Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritis Annals of the New York Academy of Sciences 1240 2011 61 69
19. C.J. Malemud Anticytokine therapy for osteoarthritis: evidence to date Drugs & Aging 27 2010 95 115
20. M. Duddy, A. Haghikia, E. Cocco, C. Eggers, J. Drulovic, O. Carmona, H. Zéphir, and R. Gold Managing MS in a changing treatment landscape Journal of Neurology 258 2011 728 739
21. R.I. Spain, M.H. Cameron, and D. Bourdette Recent developments in multiple sclerosis therapeutics BMC Medicine 7 2009 74
22. J. Wang, Y. Xiao, M. Luo, and H. Luo Statins for multiple sclerosis Cochrane Database of Systematic Reviews 2010 10.1002/14651858.CD008386.pub2 Art. No. CD008386
23. J.T. Dipiro, R.L. Talbert, G.C. Yee, G.Y. Matzke, B.J. Wells, and L.M. Posey Pharmacotherapy. A Physiologic Approach fifth ed. 2002 McGraw Hill Companies New York
24. C.D. Sarantopoulos Advances in the therapy of cancer pain: from novel experimental models to evidence-based treatments Signa Vitae 2 2007 S 23 41
25. M.H. Levy Pharmacologic treatment of cancer pain New England Journal of Medicine 335 1996 1124 1132
26. Targeted Cancer Therapies. National Cancer Institute. http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted (accessed 10.01.13)
27. G. Maggiora The reductionist paradox: are the laws of chemistry and physics sufficient for the discovery of new drugs? Journal of Computer-Aided Molecular Design 25 2011 699 708
28. C.T. Keith, A.A. Borisy, and B.R. Stockwell Multicomponent therapeutics for networked systems Nature Reviews Drug Discovery 4 2005 71 78 (Pubitemid 40109591)
29. S.A. Eisen, D.K. Miller, R.S. Woodward, E. Spitznagel, and T.R. Przybeck The effect of prescribed daily dose frequency on patient medical compliance Archives of Internal Medicine 25 1990 1881 1884 (Pubitemid 20316533)
30. C.M. Hoh, J. Dankoff, A. Colacone, and M. Afilalo Polypharmacy, adverse drug-related events, and potential adverse drug interactions in elderly patients presenting to an emergency department Annals of Emergency Medicine 38 2001 666 671 (Pubitemid 33131567)
31. A.S. Reddy, and S. Zhang Polypharmacology: drug discovery for the future Expert Review of Clinical Pharmacology 6 2013 41 47
32. R. Morphy, C. Kay, and Z. Rankovic From magic bullets to designed multiple ligands Drug Discovery Today 9 2004 641 651 (Pubitemid 38981718)
33. J.L. Medina-Franco, M.A. Giulianotti, G.S. Welmaker, and R.A. Houghten Shifting from the single to the multitarget paradigm in drug discovery Drug Discovery Today 2013 http://dx.doi.org/10.1016/j.drudis.2013.01.008
34. R. Morphy, and Z. Rankovic Designed multiple ligands. An emerging drug discovery paradigm Journal of Medicinal Chemistry 48 2005 6523 6543 (Pubitemid 41504710)
35. A. Cavalli, M.L. Bolognesi, A. Minarini, M. Rosini, V. Tumiatti, M. Recanatini, and C. Melchiorre Multi-target-directed ligands to combat neurodegenerative diseases Journal of Medicinal Chemistry 51 2008 347 372 (Pubitemid 351252260)
36. M.B. Youdim, and J.J. Buccafusco CNS targets for multi-functional drugs in the treatment of Alzheimer's and Parkinson's diseases Journal of Neural Transmission 112 2005 519 537 (Pubitemid 40562085)
37. M.B. Youdim, and J.J. Buccafusco Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders Trends in Pharmacological Sciences 26 2005 27 35 (Pubitemid 40052707)
38. J.J. Buccafusco Multifunctional receptor-directed drugs for disorders of the central nervous system Neurotherapeutics 6 2009 4 13
39. M.L. Bolognesi, R. Matera, A. Minarini, M. Rosini, and C. Melchiorre Alzheimer's disease: new approaches to drug discovery Current Opinion in Chemical Biology 13 2009 303 308
40. J. Minnerup, and W.R. Schabitz Multifunctional actions of approved and candidate stroke drugs Neurotheraprutics: Journal of the American Society for Experimental NeuroTherapeutics 6 2009 43 52
41. R. Leon, A.G. Garcia, and J.M. Contelles Recent advances in the multitarget-directed ligands approach for the treatment of Alzheimer's disease Medicinal Research Reviews 33 2013 139 189
42. K.E. Lackey The discovery of lapatinib J.R. Morphy, C.J. Harris, Designing Multi-target Drugs 2012 Royal Society of Chemistry London 181
43. J.G. Monzon, and J. Dancey Combination agents versus multi-targeted agents - pros and cons J.R. Morphy, C.J. Harris, Designing Multi-target Drugs 2012 Royal Society of Chemistry London 155
44. A. Petrelli, and S. Giordano From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage Current Medicinal Chemistry 15 2008 422 432 (Pubitemid 351472408)
45. Z. Chen, L. Han, M. Xu, Y. Xu, and X. Qian Rationally designed multitarget anticancer agents Current Medicinal Chemistry 20 2013 1694 1714
46. K.T. Liby, and M.B. Sporn Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease Pharmacological Reviews 64 2012 972 1003
47. T. Karoli, S.K. Mamidyala, J. Zuegg, S.R. Fry, E.H.L. Tee, T.A. Bradford, P.K. Madala, J.X. Huang, S. Ramu, M.S. Butler, and M.A. Cooper Structure aided design of chimeric antibiotics Bioorganic & Medicinal Chemistry Letters 22 2012 2428 2433
48. F.W. Muregi, and A. Ishih Next-generation antimalarial drugs: hybrid molecules as a new strategy in drug design Drug Development Research 71 2010 20 32
49. A. Gasco, D. Boschi, K. Chegaev, C. Cena, A. Di Stilo, R. Fruttero, L. Lazzarato, B. Rolando, and P. Tosco Multitarget drugs: focus on the NO-donor hybrid drugs Pure and Applied Chemistry 80 2008 1693 1701
50. C. Liu, X. Gu, and Y.Z. Zhu Synthesis and biological evaluation of novel leonurine-SPRC conjugate as cardioprotective agents Bioorganic & Medicinal Chemistry Letters 20 2010 6942 6946
51. L. Huang, A. Shi, F. He, and X. Li Synthesis, biological evaluation, and molecular modeling of berberine derivatives as potent acetylcholinesterase inhibitors Bioorganic & Medicinal Chemistry 18 2010 1244 1251
52. H. Jiang, X. Wang, L. Huang, Z. Luo, T. Su, K. Ding, and X. Li Benzenediol-berberine hybrids: multifunctional agents for Alzheimer's disease Bioorganic & Medicinal Chemistry 19 2011 7228 7235
53. V. Tumiatti, A. Minarini, M.L. Bolognesi, A. Milelli, M. Rosini, and C. Melchiorre Tacrine derivatives and Alzheimer's disease Current Medicinal Chemistry 17 2010 1825 1838
54. P. Dogterom, J.F. Nagelkerke, and G.J. Mulder Hepatotoxicity of tetrahydroaminoacridine in isolated rat hepatocytes: effect of glutathione and vitamin E Biochemical Pharmacology 37 1988 2311 2313
55. M.I. Fernandez-Bachiller, C. Perez, G.C. Gonzalez-Munoz, S. Conde, M.G. Lopez, M. Villarroya, A.G. GarcIa, and M.I. RodrIguez-Franco Novel tacrine-8-hydroxyquinoline hybrids as multifunctional agents for the treatment of Alzheimer's disease, with neuroprotective, cholinergic, antioxidant, and copper-complexing properties Journal of Medicinal Chemistry 53 2010 4927 4937
56. C. Galdeano, E. Viayna, I. Sola, X. Formosa, P. Camps, A. Badia, M.V. Clos, J. Relat, M. Ratia, M. Bartolini, F. Mancini, V. Andrisano, M. Salmona, C. Minguillon, G.C. Gonzalez-Munoz, M.I. Rodriguez-Franco, A. Bidon-Chanal, F.J. Luque, and D. Muñoz-Torrero Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion diseases Journal of Medicinal Chemistry 55 2012 661 669
57. P. Camps, X. Formosa, D. Munoz-Torrero, J. Petrignet, A. Badia, and M.V. Clos Synthesis and pharmacological evaluation of huprine-tacrine heterodimers: subnanomolar dual binding site acetylcholinesterase inhibitors Journal of Medicinal Chemistry 48 2005 1701 1704 (Pubitemid 40396300)
58. M.I. Fernandez-Bachiller, C. Perez, L. Monjas, J. Rademann, and M.I. Rodriguez-Franco New tacrine-4-oxo-4H-chromene hybrids as multifunctional agents for the treatment of Alzheimer's disease, with cholinergic, antioxidant, and β-amyloid-reducing properties Journal of Medicinal Chemistry 55 2012 1303 1317
59. M. Rosini, V. Andrisano, M. Bartolini, M.L. Bolognesi, P. Hrelia, A. Minarini, A. Tarozzi, and C. Melchiorre Rational approach to discover multipotent anti-Alzheimer's drugs Journal of Medicinal Chemistry 48 2005 360 363 (Pubitemid 40139781)
60. M. Rosini, E. Simoni, M. Bartolini, A. Tarozzi, R. Matera, A. Milelli, P. Hrelia, V. Andrisano, M.L. Bolognesi, and C. Melchiorre Exploiting the lipoic acid structure in the search for novel multitarget ligands against Alzheimer's disease European Journal of Medicinal Chemistry 46 2011 5435 5442
61. Y. Wang, X.-L. Guan, P.-F. Wu, C.-M. Wang, H. Cao, L. Li, X.-J. Guo, F. Wang, N. Xie, F.-C. Jiang, and J.-G. Chen Multifunctional mercapto-tacrine derivatives for treatment of age-related neurodegenerative diseases Journal of Medicinal Chemistry 55 2012 3588 3592
62. L. Fang, D. Appenroth, M. Decker, M. Kiehntopf, C. Roegler, T. Deufel, C. Fleck, S. Peng, Y. Zhang, and J. Lehmann Synthesis and biological evaluation of NO-donor-tacrine hybrids as hepatoprotective anti-Alzheimer's drug candidates Journal of Medicinal Chemistry 51 2008 713 716 (Pubitemid 351304679)
63. L. Fang, D. Appenroth, M. Decker, M. Kiehntopf, A. Lupp, S. Peng, C. Fleck, Y. Zhang, and J. Lehmann NO-donating tacrine hybrid compounds improve scopolamine-induced cognition impairment and show less hepatotoxicity Journal of Medicinal Chemistry 51 2008 7666 7669
64. M.I.R. Franco, M.I.F. Bachiller, C. Perez, B.H. Ledesma, and B. Bartolome Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer's disease, with improved acetylcholinesterase inhibitory and antioxidant properties Journal of Medicinal Chemistry 49 2006 459 462 (Pubitemid 43157478)
65. X. Chao, X. He, Y. Yang, X. Zhou, M. Jin, S. Liu, Z. Cheng, P. Liu, Y. Wang, J. Yu, Y. Tan, Y. Huang, J. Qin, S. Rapposelli, and R. Pi Design, synthesis and pharmacological evaluation of novel tacrine-caffeic acid hybrids as multi-targeted compounds against Alzheimer's disease Bioorganic & Medicinal Chemistry Letters 22 2012 6498 6502
66. R. Pi, X. Mao, X. Chao, Z. Cheng, M. Liu, X. Duan, M. Ye, X. Chen, Z. Mei, P. Liu, W. Li, and Y. Han Tacrine-6-Ferulic Acid, a novel multifunctional dimer, inhibits amyloid-β-mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo PLoS ONE 7 2012 e31921
67. X. Chen, K. Zenger, A. Lupp, B. Kling, J. Heilmann, C. Fleck, B. Kraus, and M. Decker Tacrine-silibinin codrug shows neuro- and hepatoprotective effects in vitro and pro-cognitive and hepatoprotective effects in vivo Journal of Medicinal Chemistry 55 2012 5231 5242
68. J.H.M. Lange, H.K.A.C. Coolen, M.A.W. van der Neut, A.J.M. Borst, B. Stork, P.C. Verveer, and C.G. Kruse Design, synthesis, biological properties, and molecular modeling investigations of novel tacrine derivatives with a combination of acetylcholinesterase inhibition and cannabinoid CB1 receptor antagonism Journal of Medicinal Chemistry 53 2010 1338 1346
69. L. Fang, S. Jumpertz, Y. Zhang, D. Appenroth, C. Fleck, K. Mohr, C. Trankle, and M. Decker Hybrid molecules from xanomeline and tacrine: enhanced tacrine actions on cholinesterases and muscarinic M1 receptors Journal of Medicinal Chemistry 53 2010 2094 2103
70. P.W. Elsinghorst, J.S. Cieslik, K. Mohr, C. Trankle, and M. Gutschow First gallamine-tacrine hybrid: design and characterization at cholinesterases and the M2 muscarinic receptor Journal of Medicinal Chemistry 50 2007 5685 5695 (Pubitemid 350106023)
71. Y. Chen, J. Sun, L. Fang, M. Liu, S. Peng, H. Liao, J. Lehmann, and Y. Zhang Tacrine-ferulic acid-nitric oxide (NO) donor trihybrids as potent, multifunctional acetyl- and butyrylcholinesterase inhibitors Journal of Medicinal Chemistry 55 2012 4309 4321
72. J.J. Walsh, D. Coughlan, N. Heneghan, C. Gaynor, and A. Bell A novel artemisnin-quinine hybrid with potent antimalarial activity Bioorganic & Medicinal Chemistry Letters 17 2007 3599 3602 (Pubitemid 46898817)
73. C. Cena, M.L. Lolli, L. Lazzarato, E. Guaita, G. Morini, G. Coruzzi, S.P. McElroy, I.L. Megson, R. Fruttero, and A. Gasco Antiinflammatory, gastrosparing, and antiplatelet properties of new NO-donor esters of aspirin Journal of Medicinal Chemistry 46 2003 747 754 (Pubitemid 36258866)
74. N. Hulsman, J.P. Medema, C. Bos, A. Jongejan, R. Leurs, M.J. Smit, I.J.P. de Esch, D. Richel, and M. Wijtmans Chemical insights in the concept of hybrid drugs: the antitumor effect of nitric oxide-donating aspirin involves a quinone methide but not nitric oxide nor aspirin Journal of Medicinal Chemistry 50 2007 2424 2431 (Pubitemid 46799254)
75. K.V.S. Nemmani, S.V. Mali, N. Borhade, A.R. Pathan, M. Karwa, V. Pamidiboina, S.P. Senthilkumar, M. Gund, A.K. Jain, N.K. Mangu, N.P. Dubash, D.C. Desai, S. Sharma, and A. Satyam NO-NSAIDs: gastric-sparing nitric oxide-releasable prodrugs of non-steroidal anti-inflammatory drugs Bioorganic & Medicinal Chemistry Letters 19 2009 5297 5301
76. E. Nizri, R. Adani, H. Meshulam, G. Amitai, and T. Brenner Bifunctional compounds eliciting both anti-inflammatory and cholinergic activity as potential drugs for neuroinflammatory impairments Neuroscience Letters 376 2005 46 50 (Pubitemid 40202935)
77. S. Young, K. Fabio, C. Guillon, P. Mohanta, T.A. Halton, D.E. Heck, R.A. Flowers II, J.D. Laskin, and N.D. Heindel Peripheral site acetylcholinesterase inhibitors targeting both inflammation and cholinergic dysfunction Bioorganic & Medicinal Chemistry Letters 20 2010 2987 2990
78. C.M. Doulgkeris, D. Galanakis, A.P. Kourounakis, K.C. Tsiakitzis, A.M. Gavalas, P.T. Eleftheriou, P. Victoratos, E.A. Rekkaa, and P.N. Kourounakisa Synthesis and pharmacochemical study of novel polyfunctional molecules combining anti-inflammatory, antioxidant, and hypocholesterolemic properties Bioorganic & Medicinal Chemistry Letters 16 2006 825 829 (Pubitemid 43059831)
79. X.H. Liu, H. Xin, A.J. Hou, and Y.Z. Zhu Protective effects of leonurine in neonatal rat hypoxic cardiomyocytes and rat infarcted heart Clinical and Experimental Pharmacology 36 2009 696 703
80. K.P. Loh, J. Qi, B.K. Tan, X.H. Liu, B.G. Wei, and Y.Z. Zhu Leonurine protects middle cerebral artery occluded rats through antioxidant effect and regulation of mitochondrial function Stroke 41 2010 2661 2668
81. Q. Wang, H.R. Liu, Q. Mu, P. Rose, and Y.Z. Zhu S-propargyl-cysteine protects both adult rat hearts and neonatal cardiomyocytes from ischemia/hypoxia injury: the contribution of the hydrogen sulfide-mediated pathway Journal of Cardiovascular Pharmacology 54 2009 139 146
82. C. Liu, W. Guo, X. Shi, M.A. Kaium, X. Gu, and Y. Zhun Zhu Leonurine-cysteine analog conjugates as a new class of multifunctional anti-myocardial ischemia agent European Journal of Medicinal Chemistry 46 2011 3996 4009
83. T.H. Kim, K. Kuca, D. Jun, and Y.S. Jung Design and synthesis of new bis-pyridinium oxime reactivators for acetylcholinesterase inhibited by organophosphorous nerve agents Bioorganic & Medicinal Chemistry Letters 15 2005 2914 2917 (Pubitemid 40732246)
84. B. Antonijevic, and M.P. Stojiljković Unequal efficacy of pyridinium oximes in acute organophosphate poisoning Clinical Medicine & Research 5 2007 71 78
85. J. Lovric, S. Berend, A. Lucic Vrdoljak, B. Radic, M. Katalinic, Z. Kovarik, D. Zeljezic, N. Kopjar, S. Rast, and M. Mesic A conjugate of pyridine-4-aldoxime and atropine as a potential antidote against organophosphorus compounds poisoning Acta Biochimica Polonica 58 2011 193 198
86. B.A. Weissman, and L. Raveh Multifunctional drugs as novel antidotes for organophosphates' poisoning Toxicology 290 2011 149 155
87. R.W. Buchanan, B. Kirkpatrick, N. Bryant, P. Ball, and A. Breier Fluoxetine augmentation of clozapine treatment in patients with schizophrenia American Journal of Psychiatry 153 1996 1625 1627 (Pubitemid 26406176)
88. F. Centorrino, R.J. Baldessarini, F.R. Frankenburg, J. Kando, S.A. Volpicelli, and J.G. Flodd Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors American Journal of Psychiatry 153 1996 820 822 (Pubitemid 26171680)
89. P. Smid, H.K.A.C. Coolen, H.G. Keizer, R. van Hes, J.-P. de Moes, A.P. den Hartog, B. Stork, R.H. Plekkenpol, L.C. Niemann, C.N.J. Stroomer, M.Th.M. Tulp, H.H. van Stuivenberg, A.C. McCreary, M.B. Hesselink, A.H.J. Herremans, and C.G. Kruse Synthesis, structure-activity relationships, and biological properties of 1-heteroaryl-4-[o-(1H-indol-3-yl)alkyl]piperazines, novel potential antipsychotics combining potent dopamine D2 receptor antagonism with potent serotonin reuptake inhibition Journal of Medicinal Chemistry 48 2005 6855 6869 (Pubitemid 41533107)
90. O. Weinreb, S. Mandel, O. Bar-Am, M. Yogev-Falach, Y. Avramovich-Tirosh, T. Amit, and M.B.H. Youdim Multifunctional neuroprotective derivatives of rasagiline as anti-Alzheimer's disease drugs Neurotherapeutics: the American Society for Experimental NeuroTherapeutics 6 2009 163 174
91. H. Zheng, M.B.H. Youdim, and M. Fridkin Site-activated multifunctional chelator with acetylcholinesterase and neuroprotective-neurorestorative moieties for Alzheimer's therapy Journal of Medicinal Chemistry 52 2009 4095 4098
92. A.A. Reinke, and J.E. Gestwicki Structure-activity relationships of amyloid beta-aggregation inhibitors based on curcumin: influence of linker length and flexibility Chemical Biology & Drug Design 70 2007 206 215 (Pubitemid 47305405)
93. S.-Y. Chen, Y. Li, Y.-P. Chen, S.-H. Chen, J.-H. Tan, T.-M. Ou, L.-Q. Gu, and Z.-S. Huang Design, synthesis, and biological evaluation of curcumin analogues as multifunctional agents for the treatment of Alzheimer's disease Bioorganic & Medicinal Chemistry 19 2011 5596 5604
94. P. Camps, R.E. Achab, J. Morral, D.M. Torrero, A. Badia, J.E. Banos, N.M. Vivas, X. Barril, M. Orozco, and F.J. Luque New tacrine-huperzine A hybrids (Huprines): highly potent tight-binding acetylcholinesterase inhibitors of interest for the treatment of Alzheimer's disease Journal of Medicinal Chemistry 43 2000 4657 4666
95. P. Camps, R.E. Achab, D.M. Gorbig, J. Morral, D.M. Torrero, A. Badia, J.E. Banos, N.M. Vivas, X. Barril, M. Orozco, and F.J. Luque Synthesis, in vitro pharmacology, and molecular modeling of very potent tacrine-huperzine a hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease Journal of Medicinal Chemistry 42 1999 3227 3242 (Pubitemid 29409712)
96. J. Marco-Contelles, R. Leon, C. de los RIos, A. Guglietta, J. Terencio, M.G. Lopez, A.G. GarcIa, and M. Villarroya Novel multipotent tacrine-dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer's disease Journal of Medicinal Chemistry 49 2006 7607 7610 (Pubitemid 46033653)
97. J.M. Contelles, R. Leon, C. de los RIos, A. Samadi, M. Bartolini, V. Andrisano, O. Huertas, X. Barril, F.J. Luque, M.I. RodrIguez-Franco, B. Lopez, M.G. Lopez, A.G. GarcIa, M. do Carmo Carreiras, and M. Villarroya Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer's disease Journal of Medicinal Chemistry 52 2009 2724 2732
98. I. Juranek, L. Horakova, L. Rackova, and M. Stefek Antioxidants in treating pathologies involving oxidative damage: an update on medicinal chemistry and biological activity of stobadine and related pyridoindoles Current Medicinal Chemistry 17 2010 552 570
99. M. Stefek, A. Tsantili-Kakoulidou, I. Milackova, M. Juskova, V. Snirc, and N. Triantos (2-Benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-8-yl)-acetic acid: an aldose reductase inhibitor and antioxidant of zwitterionic nature Bioorganic & Medicinal Chemistry 19 2011 7181 7185
100. R.K. Elsayed, and J.D. Evans Emerging lipid-lowering drugs: squalene synthase inhibitors Expert Opinion on Emergency Drugs 13 2008 309 322 (Pubitemid 351957350)
101. A.P. Kourounakis, C. Charitos, E.A. Rekka, and P.N. Kourounakis Lipid-lowering (hetero)aromatic tetrahydro-1,4-oxazine derivatives with antioxidant and squalene synthase inhibitory activity Journal of Medicinal Chemistry 51 2008 5861 5865
102. A.P. Kourounakis, A.N. Matralis, and A. Nikitaki Design of more potent squalene synthase inhibitors with multiple activities Bioorganic & Medicinal Chemistry 18 2010 7402 7412
103. C.J. Van der Schyf, and W.J. Geldenhuys Polycyclic compounds: Ideal drug scaffolds for the design of multiple mechanism drugs Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics 6 2009 175 186
104. D. Thomas, G. Wendt-Nordahl, K. Rockl, E. Ficker, A.M. Brown, and J. Kiehn High-affinity blockade of human ether-a-go-go-related gene human cardiac potassium channels by the novel antiarrhythmic drug BRL-32872 Journal of Pharmacology and Experimental Therapeutics 297 2001 753 761 (Pubitemid 32378009)
105. W.J. Geldenhuys, S.F. Malan, J.R. Bloomquist, and C.J. Van der Schyf Structure-activity relationships of pentacycloundecylamines at the N-methyl-D-aspartate receptor Bioorganic & Medicinal Chemistry 15 2007 1525 1532 (Pubitemid 46038121)
106. W.J. Geldenhuys, G. Terre'Blanche, C.J. Van der Schyf, and S.F. Malan Screening of novel pentacycloundecylamines for neuroprotective activity European Journal of Pharmacology 458 2003 73 79 (Pubitemid 36050703)
107. J. Kornhuber, K. Schoppmeyer, and P. Riederer Affinity of 1-aminoadamantanes for the sigma binding site in post-mortem human frontal cortex Neuroscience Letters 163 1993 129 131 (Pubitemid 24005396)
108. X. Liu, S.D. Banister, M.J. Christie, R. Banati, S. Meikle, M.J. Coster, and M. Kassiou Trishomocubanes: novel sigma ligands modulate cocaine-induced behavioural effects European Journal of Pharmacology 555 2007 37 42 (Pubitemid 46013858)
109. D.W. Oliver, T.G. Dekker, F.O. Snyckers, and T.G. Fourie Synthesis and biological activity of D3-trishomocubyl-4-amines Journal of Medicinal Chemistry 34 1991 851 854
110. D.W. Oliver, T.G. Dekker, and F.O. Snyckers Antiviral properties of 4-amino-(D3)-trishomocubanes Arzneimittelforschung 41 1991 549 552
111. rd National Meeting of American Chemical Society, Chicago 2007
112. J. Joubert, S.V. Dyk, E.R. Green, and S.F. Malan Synthesis and evaluation of fluorescent heterocyclic aminoadamantanes as multifunctional neuroprotective agents Bioorganic & Medicinal Chemistry 19 2011 3935 3944