Med Chem Res
Fang L, Gou S, Fang X, Cheng L, Fleck C (2013) Current progresses
of novel natural products and their derivatives/analogs as anti-
Alzheimer candidates: an update. Mini Rev Med Chem
Rosini M (2014) Polypharmacology: the rise of multitarget drugs over
combination therapies. Future Med Chem 6:485–487
Rosini M, Simoni E, Milelli A, Minarini A, Melchiorre C (2014)
Oxidative stress in Alzheimer's disease: are we connecting the
dots? J Med Chem 57:2821–2831
Salahuddin P, Fatima MT, Abdelhameed AS, Nusrat S, Khan RH
(2016) Structure of amyloid oligomers and their mechanisms of
toxicities: targeting amyloid oligomers using novel therapeutic
approaches. Eur J Med Chem 114:41–58
Saturnino C, Iacopetta D, Sinicropi MS, Rosano C, Caruso A,
Caporale A, Marra N, Marengo B, Pronzato MA, Parisi OI,
Longo P, Ricciarelli R (2014) N-alkyl carbazole derivatives as
new tools for Alzheimer's disease: preliminary studies. Molecules
19:9307–9317
1
3:870–887
Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's
disease: progress and problems on the road to therapeutics. Sci-
ence 297:353–356
Horton W, Sood A, Peerannawar S, Kugyela N, Kulkarni A, Tulsan R,
Tran CD, Soule J, LeVine Iii H, Török B, Török M (2017)
Synthesis and application of β-carbolines as novel multi-
functional anti-Alzheimer’s disease agents. Bioorg Med Chem
Lett 27:232–236
Huang Y, Mucke L (2012) Alzheimer mechanisms and therapeutic
strategies. Cell 148:1204–1222
Jiang D, Men L, Wang J, Zhang Y, Chickenyen S, Wang Y, Zhou F
Schneider LS, Mangialasche F, Andreasen N, Feldman H, Giacobini
E, Jones R, Mantua V, Mecocci P, Pani L, Winblad B, Kivipelto
M (2014) Clinical trials and late-stage drug development for
Alzheimer's disease: an appraisal from 1984 to 2014. J Intern
Med 275:251–283
(
2007) Redox reactions of copper complexes formed with dif-
ferent beta-amyloid peptides and their neuropathological [cor-
rection of neuropathalogical] relevance. Biochemistry
4
6:9270–9282
Leon R, Garcia AG, Marco-Contelles J (2013) Recent advances in the
multitarget-directed ligands approach for the treatment of Alz-
heimer's disease. Med Res Rev 33:139–189
Lu C, Guo Y, Yan J, Luo Z, Luo HB, Yan M, Huang L, Li X (2013)
Design synthesis and evaluation of multitarget-directed resvera-
trol derivatives for the treatment of Alzheimer's disease. J Med
Chem 56:5843–5859
Lu JJ, Pan W, Hu YJ, Wang YT (2012) Multi-target drugs: the trend of
drug research and development. PLoS One 7:e40262
MacMillan KS, Naidoo J, Liang J, Melito L, Williams NS, Morlock L,
Huntington PJ, Estill SJ, Longgood J, Becker GL, McKnight SL,
Pieper AA, De Brabander JK, Ready JM (2011) Development of
proneurogenic neuroprotective small molecules. J Am Chem Soc
Sreenivasachary N, Kroth H, Benderitter P, Hamel A, Varisco Y,
Hickman DT, Froestl W, Pfeifer A, Muhs A (2017) Discovery
and characterization of novel indole and 7-azaindole derivatives
as inhibitors of β-amyloid-42 aggregation for the treatment of
Alzheimer’s disease. Bioorg Med Chem Lett 27:1405–1411
Tang YZ, Liu ZQ (2007) Free-radical-scavenging effect of carbazole
derivatives on AAPH-induced hemolysis of human erythrocytes.
Bioorg Med Chem 15:1903–1913
Tesla R, Wolf HP, Xu P, Drawbridge J, Estill SJ, Huntington P,
McDaniel L, Knobbe W, Burket A, Tran S, Starwalt R, Morlock
L, Naidoo J, Williams NS, Ready JM, McKnight SL, Pieper AA
(2012) Neuroprotective efficacy of aminopropyl carbazoles in a
mouse model of amyotrophic lateral sclerosis. Proc Natl Acad Sci
USA 109:17016–17021
1
3:1428–1437
Naidoo J, De Jesus-Cortes H, Huntington P, Estill S, Morlock LK,
Starwalt R, Mangano TJ, Williams NS, Pieper AA, Ready JM
Thiratmatrakul S, Yenjai C, Waiwut P, Vajragupta O, Reubroycharoen
P, Tohda M, Boonyarat C (2014) Synthesis biological evaluation
and molecular modeling study of novel tacrine-carbazole hybrids
as potential multifunctional agents for the treatment of Alzhei-
mer's disease. Eur J Med Chem 75:21–30
Tsutsumi LS, Gundisch D, Sun D (2016) Carbazole scaffold in
medicinal chemistry and natural products: a review from 2010-
2015. Curr Top Med Chem 16:1290–1313
Villarroya M, Garcia AG, Marco-Contelles J, Lopez MG (2007) An
update on the pharmacology of galantamine. Expert Opin
Investig Drugs 16:1987–1998
Wang G, Han T, Nijhawan D, Theodoropoulos P, Naidoo J, Yadavalli
S, Mirzaei H, Pieper AA, Ready JM, McKnight SL (2014b) P7C3
neuroprotective chemicals function by activating the rate-limiting
enzyme in NAD salvage. Cell 158:1324–1334
(
2014) Discovery of a neuroprotective chemical (S)-N-(3-(36-
dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-
amine [(-)-P7C3-S243] with improved druglike properties. J Med
Chem 57:3746–3754
Nguyen M, Rechignat L, Robert A, Meunier B (2015) The necessity of
having a tetradentate ligand to extract copper(II) Ions from
amyloids. ChemistryOpen 4:27–31
Nguyen M, Robert A, Sournia-Saquet A, Vendier L, Meunier B (2014)
Characterization of new specific copper chelators as potential
drugs for the treatment of Alzheimer's disease. Chemistry
2
0:6771–6785
Nunomura A, Castellani RJ, Zhu X, Moreira PI, Perry G, Smith MA
2006) Involvement of oxidative stress in Alzheimer disease. J
(
Neuropathol Exp Neurol 65:631–641
Wang L, Wang R, Jin M, Huang Y, Liu A, Qin J, Chen M, Wen S, Pi
R, Shen W (2014a) Carvedilol attenuates 6-hydroxydopamine-
induced cell death in PC12 cells: involvement of Akt and Nrf2/
ARE pathways. Neurochem Res 39:1733–1740
Pieper AA, McKnight SL, Ready JM (2014) P7C3 and an unbiased
approach to drug discovery for neurodegenerative diseases. Chem
Soc Rev 43:6716–6726
Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM, Becker GL,
Huntington P, Goldman SE, Shen CH, Capota M, Britt JK, Kotti
T, Ure K, Brat DJ, Williams NS, MacMillan KS, Naidoo J,
Melito L, Hsieh J, De Brabander J, Ready JM, McKnight SL
Wang SN, Li Q, Jing MH, Alba E, Yang XH, Sabate R, Han YF, Pi
RB, Lan WJ, Yang XB, Chen JK (2016) Natural xanthones from
garcinia mangostana with multifunctional activities for the ther-
apy of alzheimer's disease. Neurochem Res 41:1806–1817
Zall A, Kieser D, Hottecke N, Naumann EC, Thomaszewski B,
Schneider K, Steinbacher DT, Schubenel R, Masur S, Baumann
K, Schmidt B (2011) NSAID-derived gamma-secretase modula-
tion requires an acidic moiety on the carbazole scaffold. Bioorg
Med Chem 19:4903–4909
Zhu D, Chen M, Li M, Luo B, Zhao Y, Huang P, Xue F, Rapposelli S,
Pi R, Wen S (2013) Discovery of novel N-substituted carbazoles
as neuroprotective agents with potent anti-oxidative activity. Eur
J Med Chem 68:81–88
(
2010) Discovery of a proneurogenic neuroprotective chemical.
Cell 142:39–51
Rampa A, Bartolini M, Bisi A, Belluti F, Gobbi S, Andrisano V,
Ligresti A, Di Marzo V (2012) The first dual ChE/FAAH inhi-
bitors: new perspectives for Alzheimer's disease? ACS Med
Chem Lett 3:182–186
Robert A, Liu Y, Nguyen M, Meunier B (2015) Regulation of copper
and iron homeostasis by metal chelators: a possible chemotherapy
for Alzheimer's disease. Acc Chem Res 48:1332–1339