Multitarget Compounds Designed for Alzheimer, Parkinson, and Huntington Neurodegeneration Diseases
Abstract
:1. Introduction
1.1. Neurodegeneration and Multitarget-Directed Ligands
1.2. Inclusion Criteria
1.3. Multitarget-Directed Ligands
1.4. Alzheimer’s Disease
1.5. Parkinson’s Disease
1.6. Huntington’s Disease
2. Multitarget Compounds Against AD
2.1. Inhibition of Cholinesterases and Aβ Aggregation
2.2. Inhibition of GSK-3β
2.3. Inhibition of HDAC
2.4. Inhibition of Cholinesterases and Histamine Antagonism
2.5. Compounds Against Neuroinflammation
2.6. Inhibition of Cholinesterases and MAOs
2.7. Compounds Against Secretases
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
AV-2 [69] | Quinazoline derivative | AChE (IC50 = 0.193 μM) BuChE (IC50 > 10 μM) BACE-1 (IC50 = 0.254 μM) Aβ self- induced aggregation inhibition (29.18–48.72%) Aβ AChE-incused aggregation inhibition (60.38–69.00%) | |
4j [66] | Cinnamamide/ester triazole hybrid | Copper-induced Aβ toxicity inhibition (EC50 = 1.39 μM) AChE inhibition | |
5s [67] | Capsaicin-tacrine hybrid | AChE (IC50 = 69.8 nM) BuChE (IC50 = 68.0 nM) BACE-1 (IC50 = 3.6 μM) | |
41 [68] | N-aryl piperazine-chalcone hybrid | AChE (IC50 = 14.84 μM) BuChE (IC50 = 41.39 μM) BACE-1 inhibition (46.60%) self- and AChE-induced Aβ1–42 aggregation inhibition | |
AK-2 [69] | Piperazine-quinazoline hybrid | AChE (IC50 = 0.283 μM) BACE-1 (IC50 = 0.231 μM) self-induced Aβ aggregation inhibition (56.11%) AChE-induced Aβ aggregation inhibition (62.88%) | |
5AD [70] | Oxadiazole-piperazine conjugate | AChE (IC50 = 0.103 μM) BACE-1 (IC50 = 1.342 μM) Self- and AChE- induced Aβ aggregation inhibition Radical scavenging activity (44.35%) | |
23a [71] | Indole-piperidine amide | AChE (IC50 = 0.32 μM) BACE-1 (IC50 = 0.39 μM) | |
1l [72] | Indol-3-yl-phenyl allylidene hydrazine carboximidamide derivative | AChE (IC50 = 60.93 μM) BACE-1 (IC50 = 9.38 μM) | |
SSZ [73] | Pyrrolopyridine and N-cyclohexyl hybrid | BuChE BACE-1 γ-secretase MAO-A MAO-B |
2.8. Compounds Against MAO-B
2.9. Inhibition of Cholinesterases
2.10. Antagonism of NMDA Receptors
2.11. Inhibition of MAO and Carbonic Anhydrase
2.12. Compounds Against Cholinesterases, Diabetes, Cancer, and Inflammation
2.13. Compounds Against Ca2+ Channels, Nrf2 Pathway, Cathepsin S Enzyme, and Oxidation
2.14. Inhibition of MAO and Xanthine Oxidase
3. Multitarget Compounds Against PD
3.1. Compounds with Neuroprotective Potential
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
NOA [90] | 10-nitro-oleic acid | Oxidative stress α-syn NOX2 inhibition LRRK2 inhibition | |
J24335 [93] | Quinoline derivative | CREB/PGC-1α/NRF-1/TFAM PKA/Akt/GSK-3β | |
3h [94] | Benzimidazole arylhydrazone derivative | Oxidative stress MAO-B inhibition |
3.2. Compounds Against Neuroinflammation
3.3. Compounds Against MAO-B and Other Pathological Targets
3.4. Compounds Against Cholinesterases, MAOs, and Other Pathological Targets
3.5. Compounds Against Alpha-Synuclein (α-Syn) and Other Pathological Targets
3.6. Agonism of Dopamine Receptor and Antagonism of Adenosine Receptor
3.7. Agonism of Histamine Receptor and Antagonism of Adenosine Receptor
4. Multitarget Compounds Against HD
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
AD | Alzheimer’s Disease |
HD | Huntington’s Disease |
PD | Parkinson’s diseases |
Aβ | Amyloid-beta peptides |
AChEI | Acetylcholinesterase inhibitors |
ACh | Acetylcholine |
NMDA | N-methyl-D-aspartate |
THA | Tacrine |
ATP | Adenosine Triphosphate |
ChEs | Cholinesterases |
MAO | Monoamine oxidase |
COMT | Catechol-O-methyltransferase |
L-DOPA | L-3,4-Dihydroxyphenylalanine |
MTDLs | Multitarget-directed ligands |
ΒΒΒ | Blood–brain barrier |
AchE | Acetylcholinesterase |
BuChE | Butyrylcholinesterase |
CAS | Catalytic active site |
PAS | Peripheral anionic site |
IC50 | Inhibitory Concentration 50 |
EC50 | Effective Concentration 50 |
SH-SY5Y | SK-N-SH human neuroblastoma cell lines |
Neuro2A | Neuroblastoma-2A cell lines |
PC12 | Pheochromocytoma cell line 12 |
PAMPA | parallel artificial membrane permeability assay |
ROS | Reactive Oxygen Species |
NLRP30 | Nucleotide-binding Oligomerization Domain like receptor 30 |
SAR | Structure–activity relationship |
VEGF | Vascular endothelial growth factor |
BV2 | Murine microglial cell line |
GSK-3β | Glycogen synthase kinase-3β |
DYRK1A | Dual-specificity tyrosine phosphorylation-regulated kinase 1A |
NFTs | Neurofibrillary tangles |
HL-7702 | Human liver 7702 cell lines |
HepG2 | Hepatocellular Gep 2 cells |
THLE2 | Telomerase-Immortalized Human Liver Epithelial Cells 2 |
CDK2 | Cyclin-Dependent Kinase 2 |
HDAC | Histone Deacetylase |
CAP | Catabolite activator protein |
TNF-α | Tumor Necrosis Factor Alpha |
IFN-γ | Interferon Gamma |
A1 | Astrocytes |
H3R | Antagonism histamine H3 receptor |
ADME | Absorption, Distribution, Metabolism, and Excretion |
Ki | Inhibition constant |
hCMEC/D3 | Human cerebral microvascular endothelial cells |
hPepT1-MDCK | Human Peptide Transporter 1 Madin-Darby Canine Kidney cells |
FAAH | Fatty-acid amide hydrolase 1 |
LOX | Lipoxygenase |
COX2 | Cyclooxygenase-2 |
BACE-1 | Beta-site Amyloid precursor protein Cleaving Enzyme-1 |
APP | Amyloid Precursor Protein |
NF-κΒ | Nuclear Factor kappa-light-chain-enhancer of activated B cells |
IL | Interleukin |
CHL | Chinese Hamster Lung Cell Assay |
CA | Carbonic anhydrase |
FDA | Food and Drug Administration |
Caco-2 | Human colon carcinoma cell line |
Nrf2 | Nuclear factor erythroid 2-related factor 2 |
CatS | Cathepsin S |
Keap1 | Kelch-like ECH-associated protein 1 |
ARE | Antioxidant Response Element |
AREc32 | Antioxidant Response Element cell line 32 |
CD | Concentration |
NOX2 | NADPH oxidase isoform 2 |
NADPH | Nicotinamide Adenine Dinucleotide Phosphate |
LRRK2 | Leucine-rich repeat kinase 2 |
N27-A | Mouse midbrain dopaminergic neuronal cell lines |
CYP3A4 | Cytochrome P450 3A4 |
Δψm | Mitochondrial Membrane Potential |
6-OHDA | 6-hydroxydopamine |
CREB | cAMP Response Element-Binding Protein |
PGC-1α | Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha |
NRF-1 | Nuclear Respiratory Factor 1 |
TFAM | Transcription Factor A Mitochondria |
PKA | Protein Kinase A |
Akt | Protein Kinase B |
MAPK | Mitogen-activated protein kinase |
HT-22 | Mouse hippocampal cell lines |
NO | Nitric Oxide |
LPS | Lipopolysaccharide |
MCF-7 | Michigan Cancer Foundation breast cancer cell lines |
HCT116 | human colon cancer cell lines 116 |
SK-OV-3 | Sankyo Ovarian 3 human ovarian adenocarcinoma cell lines |
GABAA | γ-aminobutyric acid A |
α-syn | Alpha-synuclein |
FI | Fluorescence Intensity |
A2AR | Adenosine A2A receptor |
D2R | Dopamine receptor |
LIMK-2 | LIM-domain-containing protein kinase 2 |
DHODH | Dihydroorotate dehydrogenase |
JNKs | c-Jun N-terminal kinases |
NMDAR | N-Methyl-D-Aspartate Receptor |
CB2 | Cannabinoid receptor 2 |
TrkB | Tropomyosin receptor-kinase B |
TrkC | Tropomyosin receptor-kinase C |
LM22B-10 | Microglial cell lines |
A2AAR | Antagonism of A2A adenosine receptor |
PDE | Phosphodiesterase |
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Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
5a3 [36] | Rivastigmine-indole hybrid | AChE (IC50 = 10.9 μM) BuChE (IC50 = 10.4 μM) Aβ42 self-aggregation inhibition (50.3%) Antioxidant activity (EC50 = 14.5 μM) | |
5c3 [36] | Rivastigmine-indole hybrid | AChE (IC50 = 26.8 μM) BuChE (IC50 = 14.9 μM) Aβ42 self-aggregation inhibition (55.5%) Antioxidant activity (EC50 = 20.7 μM) | |
1 [37] | Benzothiazole-piperazine hybrid | AChE (IC50 = 0.42 μM) Aβ1–42 self-aggregation inhibition (80.7%) | |
10 [38] | Thiazole-clubbed piperazine derivative | AChE (IC50 = 0.151 μM) BuChE (IC50 = 0.135 μM) Aβ1–42 self-aggregation inhibition (73.53%) | |
20 [38] | Thiazole-clubbed piperazine derivative | AChE (IC50 = 0.499 μM) BuChE (IC50 = 0.103 μM) Aβ1–42 self-aggregation inhibition (79.42%) | |
13α [39] | Ferulic acid-piperazine derivative | AChE (IC50 = 0.59 μM) BuChE (IC50 = 5.02 μM) Antioxidant activity (IC50 = 5.88 μM) Aβ metal-induced and self-aggregation inhibition | |
AM5 [40] | Quinolinone hybrid | AChE (IC50 = 1.29 μM) Aβ42 aggregation inhibition (IC50 = 4.93 μM) Antioxidant activity | |
AM10 [40] | Quinolinone hybrid | AChE (IC50 = 1.72 μM) Aβ42 aggregation inhibition (IC50 = 1.42 μM) Antioxidant activity | |
3b-1 [41] | L-tryptophan derivative | BuChE (IC50 = 0.44 μM) Aβ1–42 self-aggregation inhibition (52.50%) Radical scavenging (IC50 = 0.72 μM) | |
5a [42] | 5-substituted-2-anilino-1,3,4-oxadiazole derivative | AChE (IC50 = 46.9 nM) BuChE (IC50 = 3.5 nM) Aβ self-aggregation inhibition Antioxidant activity | |
6b [43] | Melatonin–mydroxyquinoline hybrid | Aβ Cu-induced and self-aggregation inhibition (63.24%) Radical scavenging | |
6c [43] | Melatonin–mydroxyquinoline hybrid | Aβ Cu-induced and self-aggregation inhibition (40.33%) Radical scavenging |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
ZLQH-5 [44] | Harmine derivative | GSK-3β (IC50 = 66 nM) DYRK1A (IC50 = 111 nM) tau hyperphosphorylation inhibition | |
18a [45] | Tetrahydroacridin hybrid with sulfur-inserted linker | GSK-3β (IC50 = 0.930 μM) AChE (IC50 = 0.047 μM) | |
7c [46] | Quianolin-2-one derivative | GSK-3β (IC50 = 6.68 nM) tau aggregation inhibition |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
4 [47] | Benzothiazepine derivative | GSK-3β (IC50 = 0.142 μM) HDAC2 (IC50 = 0.030 μM) HDAC6 (IC50 = 0.045 μM) | |
W5 [48] | Carboxamidoxime derivative | HDAC6 inhibition | |
LASSBio-1911 [49] | Benzohydrazide hybrid | HDAC inhibition |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
2 [50] | Pitolisant-sulfonylureas derivative | AChE (IC50 = 7.65 μM) H3R antagonism (IC50 = 0.13 μM) | |
ADS031 [51] | 4-oxypiperidine ether derivatives | H3R (Ki = 12.5 nΜ) AChE (IC50 = 1.537 μM) BuChE (IC50 = 1.353 μM) | |
11l [52] | Scutellarein 7 L-amino acid carbamate-4′-cycloalkylamine propyl ether conjugate | AChE (IC50 = 9.73 μM) H3R (IC50 = 1.09 nM) |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
7a [53] | N-substituted pyrrolidine derivative | AChE (IC50 = 0.215 μM) FAAH (IC50 = 8.2 μM) Antioxidant activity (IC50 = 0.4 μM) | |
14g [53] | N-substituted pyrrolidine derivative | BuChE (IC50 = 0.155 μM) FAAH (IC50 = 0.94 μM) Antioxidant activity (IC50 = 42.7 μM) | |
18a [54] | Cinnamic amide hybrid | Lipid peroxidation inhibition (99%) | |
28c [54] | Cinnamic amide hybrid | LOX-1 (IC50 = 8.5 μM) | |
22a [54] | Cinnamic amide hybrid | COX-2 (IC50 = 5 μM) | |
23c [54] | Cinnamic amide hybrid | LOX-1 COX-2 | |
SR42 [55] | Tryptamine derivative | AChE (IC50 = 0.70 μM) MAO-B (IC50 = 43.21 μM) COX-2 (75.16%) | |
S-12 [56] | Diaryl triazine hybrid | AChE (IC50 = 0.486 μM) BACE-1 (IC50 = 0.542 μM) Aβ1–42 aggregation inhibition (81.1%) | |
S-02 [56] | Diaryl triazine hybrid | DYRK1A (IC50 = 2 μM) | |
7b [57] | Quinazolinone-based hybrid | AChE inhibition (23.8%) anti-inflammatory antioxidant activity | |
3n [58] | Bakuchiol–coumarin hybrid | AChE (IC50 = 34.78 μM) TNF-α (53.89%) IL-6 (86.53%) | |
n1 [59] | Tryptanthrin hybrid | AChE (IC50 = 12.17 nM) Aβ1–42 aggregation inhibition NO (IC50 = 2.13 μM) IL-1β (IC50 = 2.21 μM) TNF-α (IC50 = 2.47 μM) |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
7d [60] | Tacrine-selegiline hybrid | AChE (IC50 = 1.57 μM) BuChE (IC50 = 0.43 μM) MAO-A (IC50 = 2.3 μM) MAO-B (IC50 = 4.75 μM) | |
3b [61] | 1,2,4-oxadiazole derivative | AChE (IC50 = 0.02330 μM) MAO-B (IC50 = 140.02 μM) Antioxidant activity (IC50 = 536.83 μM) | |
1a [61] | 1,2,4-oxadiazole derivative | MAO-A (IC50 = 47.25 μM) | |
2b [61] | 1,2,4-oxadiazole derivative | AChE (IC50 = 0.03393 μM) | |
a12 [62] | Quinoline-base sulfonamide hybrid | AChE (IC50 = 2.65 μM) BuChE (IC50 = 1.16 μM) MAO-A (IC50 = 1.34 μM) MAO-B (IC50 = 0.47 μM) | |
4kk [63] | Chromen-2-one based piperidine hybrid | AChE BuChE MAO-A MAO-B | |
5a [64] | 3-phenylcoumarin derivative | AChE BuChE MAO-A MAO-B |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
VN-19 [74] | Chromone derivative | AChE (IC50 = 140 nM) BuChE (IC50 = 11.6 μM) MAO-B (IC50 = 450 nM) Aβ self-induced aggregation (47.3%) Antioxidant activity (68.44%) | |
XYY-CP1106 [75] | Hydroxypyridinone-coumarin hybrid | Iron chelation (pFe3+ = 18.04) MAO-B (IC50 = 14.7 nM) | |
30 [76] | 6-hydroxybenzothiazol-2-carboxamid derivative | MAO-B (IC50 = 41 nM) tau and α-synuclein aggregation reduction |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
4h [77] | N′-(quinolin-4-ylmethylene)propanehydrazide hybrid | AChE (IC50 = 7.04 μM) BuChE (IC50 = 16.06 μM) | |
4c [78] | Piperazine-2-carboxylic acid derivative | AChE (Ki = 10.2 μM) | |
7b [78] | Piperazine-2-carboxylic acid derivative | BuChE (Ki = 1.6 μM) | |
8n [79] | Isatin-triazine-aniline hybrid | AChE (IC50 = 0.2 nM) BuChE (IC50 = 0.03 μM) Metal chelation | |
8c [79] | Isatin-triazine-aniline hybrid | AChE BuChE Antioxidant activity (EC50 = 64.4 μM) | |
16 [80] | Tacrine derivative | AChE (IC50 = 156.0 nM) BuChE (IC50 = 82.5 nM) | |
HupA-A1 [81] | Huperzine A hybrid | AChE inhibition Metal chelation | |
6j [82] | Piperic acid derivative | AChE (IC50 = 2.13 μM) BuChE (IC50 = 28.19 μM) Antioxidant activity | |
95 [83] | Piperazine-quinoline hybrid | AChE (IC50 = 3.013 μM) BuChE (IC50 = 3.144 μM) Antioxidant activity Metal chelation |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
5c [84] | Amiridine hybrid | BuChE (IC50 = 0.6 μM) NMDA antagonism | |
5d [84] | Amiridine hybrid | BuChE (IC50 = 0.1 μM) NMDA antagonism | |
I-52 [85] | Phenoxytacrine derivative | AChE (IC50 = 8.52 μM) BuChE (IC50 = 5.48 μM) NMDA receptor antagonism (IC50 = 2.4 μM) |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
45 [86] | Coumarin-benzesulfonamide hybrid | MAO-B (IC50 = 9.1 nM) CA (Ki = 0.1–90.0 nM) | |
47 [86] | Coumarin-benzesulfonamide hybrid | MAO-B (IC50 = 6.7 nM) CA (Ki = 0.1–90.0 nM) | |
75 [86] | Coumarin-benzesulfonamide hybrid | MAO-B (IC50 = 6.7–32.6 nM) CA (Ki = 0.1–90.0 nM) | |
84 [86] | Coumarin-benzesulfonamide hybrid | MAO-B (IC50 = 6.7–32.6 nM) CA (Ki = 0.1–90.0 nM) |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
7f [87] | Pyrazole-based Schiff bases hybrid | AChE (IC50 = 62.11 μM) α-amylase inhibition α-glucosidase inhibition |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
4i [88] | Dihydropyridine derivative | Ca-channel blockage (11%) Induce Nrf2 activation Antioxidant activity CatS (Ki = 69.3 μΜ) |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
HT3 [89] | Hydroxytyrosol derivatives of donepezil | MAO-A (IC50 = 23.4 μM) MAO-B (IC50 = 171.0 μM) Xanthine oxidase inhibition | |
HT2 [89] | Hydroxytyrosol derivatives of donepezil | MAO-A inhibition MAO-B inhibition Xanthine oxidase inhibition |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
4 [5] | N-methyl-N-propargyl derivative | p38α-MAPK (IC50 = 98.7 nM) | |
2j [96] | Carbamylated tryptamine hybrid | BuChE (IC50 = 6.77 nM) COX-2 inhibition | |
14 [97] | Indole derivative | NRF2 (CD = 5.07 μM) MAO-B (IC50 = 17.0 μM) IL-1β reduction (41.1%) Antioxidant activity | |
4d [98] | Styryl sulfone hybrid | NO inhibition (94.0%) p38 MAPK NF-κB Nrf2 |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
30 [76] | 6-hydroxybenzothiazol-2-carboxamide | MAO-B (IC50 = 0.041 μM) tau (EC50 = 10.5 μM) α-syn (IC50 = 9.09 μM) | |
8 [99] | Caffeic acid derivative | COMT (IC50 = 1.33 μM) MAO-B (IC50 = 4.27 μM) | |
7 [92] | Benzimidazole hybrid | MAO-B inhibition | |
8a [100] | Indole derivative | MAO-B (IC50 = 0.02 μM) | |
3n [101,102] | Melatonin hybrid | MAO-B (IC50 = 1.41 μM) |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
9 [102] | Coumarin derivative | MAO-B (IC50 = 0.007 μM) CA inhibition AChE inhibition BuChE inhibition | |
5a [103] | Rivastigmine-benzimidazole hybrid | Aβ42 self- and Cu-induced aggregation inhibition (45%) AChE inhibition BuChE inhibition Metal chelation Antioxidant activity | |
4b [104] | 1,3,4-oxadiazole derivative | AChE (IC50 = 0.83 μM) MAO-A (IC50 = 1.44 μM) MAO-B (IC50 = 1.04 μM) | |
3a [105] | 1H-chromeno[3,2-c]pyridine derivative | AChE (IC50 = 6.79 μM) MAO-A (IC50 = 8.42 μM) MAO-B (IC50 = 0.510 μM) | |
6c [105] | 1H-chromeno[3,2-c]pyridine derivative | AChE MAO-A MAO-B | |
2a [106] | 2′-hydroxychalcone derivative | MAO-B (IC50 = 0.111 μM) Aβ1–42 aggregation inhibition (75.7%) GABAA receptor (Ki = 5.0 μM) AChE inhibition | |
10 [107] | 7-amidocoumarin derivative | MAO-A MAO-B AChE BuChE BACE-1 |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
10 [108] | Indole triazine derivative | α-syn aggregation inhibition (FI = 13.5%), tau aggregation inhibition hyperphosphorylated tau oligomerization inhibition | |
PQQ [109] | Pyrroloquinoline quinone | Antioxidant activity α-syn Cu-induced aggregation inhibition | |
24b [110] | Hydroxybenzothiazole hybrid | Dyrk1A inhibition α-syn aggregation inhibition tau aggregation inhibition |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
30 [111] | Benzothiazole derivative | A2AR (Ki = 0.16 μΜ)
D2R (Ki = 0.37 μΜ) |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
12 [112] | Benzimidazolone derivative | A1R A2AR H3R |
Molecule | Molecule Name | Chemical Class | Primary Targets |
---|---|---|---|
3d [113] | 3-aryl-5,6-dihydrobenzo[h]cinnoline derivative | AChE BuChE MAO-A MAO-B LIMK-2 | |
3h [113] | 3-aryl-5,6-dihydrobenzo[h]cinnoline derivative | AChE BuChE MAO-A MAO-B DHODH NMDAR JNKs | |
5p [114] | Quinoline hybrid | AChE BuChE CB2 agonism | |
LM22B [115] | Triarylmethane derivative | TrkB TrkC AKT | |
11b [116] | Xanthine derivative | MAO-B (IC50 = 47.9 nM) A2AR (Ki = 0.672 μM) | |
11d [116] | Xanthine derivative | PDE4B1 (IC50 = 2.44 μM) PDE10A (IC50 = 2.30 μM) |
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Share and Cite
Katsoulaki, E.-E.; Dimopoulos, D.; Hadjipavlou-Litina, D. Multitarget Compounds Designed for Alzheimer, Parkinson, and Huntington Neurodegeneration Diseases. Pharmaceuticals 2025, 18, 831. https://doi.org/10.3390/ph18060831
Katsoulaki E-E, Dimopoulos D, Hadjipavlou-Litina D. Multitarget Compounds Designed for Alzheimer, Parkinson, and Huntington Neurodegeneration Diseases. Pharmaceuticals. 2025; 18(6):831. https://doi.org/10.3390/ph18060831
Chicago/Turabian StyleKatsoulaki, Eleftheria-Emmanouela, Dimitrios Dimopoulos, and Dimitra Hadjipavlou-Litina. 2025. "Multitarget Compounds Designed for Alzheimer, Parkinson, and Huntington Neurodegeneration Diseases" Pharmaceuticals 18, no. 6: 831. https://doi.org/10.3390/ph18060831
APA StyleKatsoulaki, E.-E., Dimopoulos, D., & Hadjipavlou-Litina, D. (2025). Multitarget Compounds Designed for Alzheimer, Parkinson, and Huntington Neurodegeneration Diseases. Pharmaceuticals, 18(6), 831. https://doi.org/10.3390/ph18060831