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Serotonin 5-HT6 Receptor Antagonists in Alzheimer’s Disease: Therapeutic Rationale and Current Development Status

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Current Pharmacotherapy and Multi-Target Approaches for Alzheimer’s Disease

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Multiple roles of fucoxanthin and astaxanthin against Alzheimer's disease: Their pharmacological potential and therapeutic insights

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Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer’s disease

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Modulating 5-Ht 4 and 5-Ht 6 Receptors in Alzheimer’S Disease Treatment

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The recent development of donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's agents: highlights from 2010 to 2020

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Isosteroidal alkaloids as potent dual-binding site inhibitors of both acetylcholinesterase and butyrylcholinesterase from the bulbs of Fritillaria walujewii

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Indole-Based Compounds in the Development of Anti-Neurodegenerative Agents

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Liquiritigenin ameliorates memory and cognitive impairment through cholinergic and BDNF pathways in the mouse hippocampus

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Novel Multitarget-Directed Ligands Aiming at Symptoms and Causes of Alzheimer’s Disease

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Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer’s Disease

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Tacrine-Based Hybrids: Past, Present, and Future

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Chlorinated tacrine analogs: Design, synthesis and biological evaluation of their anti-cholinesterase activity as potential treatment for Alzheimer’s disease

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Novel deoxyvasicinone derivatives as potent multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation

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Sulfonamides: Synthesis and the recent applications in Medicinal Chemistry

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Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present)

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Multi-target-directed-ligands acting as enzyme inhibitors and receptor ligands

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Sulfur-containing therapeutics in the treatment of Alzheimer’s disease

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Recent advances in multitarget-directed ligands targeting G-protein-coupled receptors

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Neuro-nutrients as anti-alzheimer's disease agents: A critical review

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Pleiotropic prodrugs: Design of a dual butyrylcholinesterase inhibitor and 5-HT6 receptor antagonist with therapeutic interest in Alzheimer's disease.

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Discovery of potent glycogen synthase kinase 3/cholinesterase inhibitors with neuroprotection as potential therapeutic agent for Alzheimer’s disease

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Synthesis, biological evaluation and modeling of hybrids from tetrahydro-1H-pyrazolo[3,4-b]quinolines as dual cholinestrase and COX-2 inhibitors

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In-silico Design, ADMET Screening, Prime MM-GBSA Binding Free Energy Calculation and MD Simulation of Some Novel Phenothiazines as 5HT6R Antagonists Targeting Alzheimer’s Disease

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Design, Synthesis, and Biological Evaluation of Dual-Target Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 9A (PDE9A) for the Treatment of Alzheimer’s Disease

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Modern Tools and Techniques in Computer-Aided Drug Design

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Novel 3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole-Based Multifunctional Ligands with Antipsychotic-Like, Mood-Modulating, and Procognitive Activity

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Donepezil Derivatives Targeting Amyloid-β Cascade in Alzheimer's Disease

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Development and crystallography-aided SAR studies of multifunctional BuChE inhibitors and 5-HT6R antagonists with β-amyloid anti-aggregation properties

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Design, synthesis and evaluation of dihydropyranoindole derivatives as potential cholinesterase inhibitors against Alzheimer’s disease

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A dual-acting 5-HT6 receptor inverse agonist/MAO-B inhibitor displays glioprotective and pro-cognitive properties

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Discovery of 1-(phenylsulfonyl)-1H-indole-based multifunctional ligands targeting cholinesterases and 5-HT6 receptor with anti-aggregation properties against amyloid-beta and tau

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Anti‐Alzheimer's multitarget‐directed ligands with serotonin 5‐HT6 antagonist, butyrylcholinesterase inhibitory, and antioxidant activity

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Antitubercular and Antiparasitic 2-Nitroimidazopyrazinones with Improved Potency and Solubility

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New piperazine-based bis(thieno[2,3- b ]pyridine) and bis(pyrazolo[3,4- b ]pyridine) hybrids linked to benzofuran units: Synthesis and in vitro screening of potential acetylcholinesterase inhibitors

Ahmed, A. A. M., Mekky, A. E. M., & Sanad, S. M. H. (2022) · Synthetic Communications · doi:10.1080/00397911.2022.2056853 · Cited by 23 · see citing works

Synthesis and pharmacological evaluation of multi-functional homoisoflavonoid derivatives as potent inhibitors of monoamine oxidase B and cholinesterase for the treatment of Alzheimer's disease

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Serotonin type 6 receptor antagonist attenuates the impairment of long-term potentiation and memory induced by Abeta

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Novel thiazole‐piperazine derivatives as potential cholinesterase inhibitors

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Innovative pathological network‐based multitarget approaches for Alzheimer's disease treatment

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Synthesis of Chromone‐Containing Allylmorpholines through a Morita–Baylis–Hillman‐Type Reaction

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Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with In Vitro and In Vivo Activity in Neurodegenerative Diseases

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Multidirectional in vitro and in cellulo studies as a tool for identification of multi-target-directed ligands aiming at symptoms and causes of Alzheimer’s disease

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Synthesis of new lophine–carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling

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Hybrid molecules combining GABA-A and serotonin 5-HT6 receptors activity designed to tackle neuroinflammation associated with depression

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Novel tetrahydroacridine derivatives with iodobenzoic acid moiety as multifunctional acetylcholinesterase inhibitors

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Multitarget Anti-Alzheimer Hybrid Compounds

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New bis(pyrazolo[3,4-b]pyridines) and bis(thieno[2,3-b]pyridines) as potential acetylcholinesterase inhibitors: synthesis, in vitro and SwissADME prediction study

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Discovery of novel multifunctional ligands targeting GABA transporters, butyrylcholinesterase, β-secretase, and amyloid β aggregation as potential treatment of Alzheimer's disease

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A Review on the Arylpiperazine Derivatives as Potential Therapeutics for the Treatment of Various Neurological Disorders

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Anticholinesterase Agents For Alzheimer's Disease Treatment: An Updated Overview

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Discovery of blood-brain barrier permeable and orally bioavailable caffeine-based amide derivatives as acetylcholinesterase inhibitors

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2D QSAR, design, docking study and ADMET of some N-aryl derivatives concerning inhibitory activity against Alzheimer disease

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Synthesis and evaluation of 26-amino acid methyl ester substituted sarsasapogenin derivatives as neuroprotective agents for Alzheimer’s disease

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Multifunctional Ligands Targeting Phosphodiesterase as the Future Strategy for the Symptomatic and Disease-Modifying Treatment of Alzheimer’s Disease

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Design, Synthesis, and In Vitro Biological Activities of a Bio-Oxidizable Prodrug to Deliver Both ChEs and DYRK1A Inhibitors for AD Therapy

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Multifunctional 6-fluoro-3-[3-(pyrrolidin-1-yl)propyl]-1,2-benzoxazoles targeting behavioral and psychological symptoms of dementia (BPSD)

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Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases

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Potential role of herbal plants and beta sitosterol as a bioactive constituent in circumventing Alzheimer’s Disease

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Novel thienocycloalkylpyridazinones as useful scaffolds for acetylcholinesterase inhibition and serotonin 5-HT6 receptor interaction

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Efficient Microwave Synthesis, Antibacterial, and Antifungal Evaluation of 1,4-Dihydropyrimido[1,2-a]benzimidazole Derivatives

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Design, Synthesis and Biological Evaluation of Novel 2‐Phenylthiazole Derivatives for the Treatment of Alzheimer's Disease

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Design of Multi-target Directed Ligands as a Modern Approach for the Development of Innovative Drug Candidates for Alzheimer’s Disease

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Serotonin 5-HT6 Receptor Ligands and Butyrylcholinesterase Inhibitors Displaying Antioxidant Activity—Design, Synthesis and Biological Evaluation of Multifunctional Agents against Alzheimer’s Disease

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Multifunctional Ligand Approach: Search for Effective Therapy Against Alzheimer’s Disease

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Neuroprotective role of herbal alternatives in circumventing Alzheimer’s disease through multi-targeting approach - a review

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Medicinal chemistry approaches for dual inhibition of amyloid-β and tau aggregation in Alzheimer’s disease

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Computational Modeling of Drugs for Alzheimer’s Disease: Design of Serotonin 5-HT6 Antagonists

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Design, synthesis and SAR of novel naphthalene–sulfonamide hybrids: anticancer assessment, gene expression analysis of IL6/JAK2/STAT3 signaling in MCF7 cells and antimicrobial evaluation

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Multitarget-Directed Ligands Hitting Serotonin Receptors: A Medicinal Chemistry Survey

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Investigation of Methylsulfonamide’s Capability to Prevent Zn 2+ -Induced Aβ Peptide Aggregation Based on Zn 2+ Coordination within the Zinc Binding Region of Aβ for Treatment of Alzheimer’s Disease (AD)

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Idalopirdine (LY483518, SGS518, Lu AE 58054) in Alzheimer disease: never change a winning team and do not build exclusively on surrogates. Lessons Learned from Drug Development Trials

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Ionophoric polyphenols are permeable to the blood–brain barrier, interact with human serum albumin and Calf Thymus DNA, and inhibit AChE enzymatic activity

Martínez, A., Zahran, M., Gomez, M., Guevara, J., Pichardo-Bueno, R., Asim, J., Ortiz, G., Andoh, Y., Shibutani, S., & Kaur, B. (2020) · Medicinal Chemistry Research · doi:10.1007/s00044-020-02615-3 · Cited by 4 · see citing works

Synthesis of C4-functionalized 1,2,3,4-tetrahydroacridine-based Pfitzinger acid derivatives in deep eutectic solvents and their biological evaluation as dual cholinesterase and α-glucosidase inhibitors

Shirisha, T., Majhi, S., Divakar, K., & Kashinath, D. (2024) · New Journal of Chemistry · doi:10.1039/d4nj04137b · Cited by 3 · see citing works

Discovery of small molecules for the treatment of Alzheimer’s disease

Rao, P. P. N., Pham, A. T., & Shakeri, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818349-6.00011-x · Cited by 3 · see citing works

Contilistat, a New Multitarget Small Polyfunctionalized Indole Derivative

Hansen, F. K., Marco, J. L., Toledano‐Pinedo, M., Diez‐Iriepa, D., Porro-Pérez, A., Schäker‐Hübner, L., Hanl, M., Samadi, A., Almendros, P., Iriepa, I., et al. (2024) · Synlett · doi:10.1055/s-0043-1775419 · Cited by 2 · see citing works

Water soluble biguanide salts and their 1,3,5-triazine derivatives as inhibitors of acetylcholinesterase and α-glucosidase

Güngör, Ö., Kurtar, S. N. K., & Köse, M. (2020) · Zeitschrift für Kristallographie - Crystalline Materials · doi:10.1515/zkri-2020-0025 · Cited by 2 · see citing works

Synthesis, Crystal Structure and Biological Evaluation of Novel 2-Phenylthiazole Derivatives as Multi-Targeting Agents to Treat Alzheimer's Disease

Shi, D., Tang, Z.-M., Ma, X., Min, W., Xu, X., Liu, Y., Song, X., Liu, W., & Song, M. (2017) · Journal of Chemical Research · doi:10.3184/174751917x15045169836217 · Cited by 2 · see citing works

The Potential of Herbal Plants and Bioactive β Sitosterol in Circumventing Alzheimer’s Disease – A Review

Mishra, A., Das, S., Kumari, S., Kanda, A., & Prabhakar, V. (2023) · Journal of Natural Remedies · doi:10.18311/jnr/2023/32973 · Cited by 1 · see citing works

Evolution of Multitarget Strategies for Alzheimer’s Disease: From Cholinergic Inhibition to Network-Oriented Therapeutic Design (2006–2025)

Mella, J., Vega-Muñoz, A., Soto, M., Moraga, D., Campanini-Salinas, J., Sandoval-Obando, E., Contreras-Barraza, N., Salazar-Sepúlveda, G., Salas, N., Carabantes-Silva, R., et al. (2026) · Pharmaceuticals · doi:10.3390/ph19071024 · Cited by 1 · see citing works

Computer-Aided Design of Ligands at Multiple Protein Targets for Multifactorial Diseases

Kalash, L. N. (2018) · Apollo (University of Cambridge) · doi:10.17863/cam.38293

Additional file 1 of 2D QSAR, design, docking study and ADMET of some N-aryl derivatives concerning inhibitory activity against Alzheimer disease

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In vitro and in silico evaluation of human serum albumin binding, blood-brain barrier permeability, and acetylcholinesterase inhibition by multi-target compounds with potential anti-Alzheimer’s disease properties

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BindingDB Entry 50019597: Discovery of novel multifunctional ligands targeting GABA transporters, butyrylcholinesterase, β-secretase, and amyloid β aggregation as potential treatment of Alzheimer's disease.

BindingDB (2024) · UC San Diego · doi:10.7270/q2wm1js6

BindingDB Entry 50002330: Novel deoxyvasicinone derivatives as potent multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation.

BindingDB (2020) · UC San Diego · doi:10.7270/q2vt1vqs

BindingDB Entry 50018950: Novel thienocycloalkylpyridazinones as useful scaffolds for acetylcholinesterase inhibition and serotonin 5-HT

BindingDB (2024) · UC San Diego · doi:10.7270/q2fr01vv

BindingDB Entry 50019997: Hybrid molecules combining GABA-A and serotonin 5-HT

BindingDB (2024) · UC San Diego · doi:10.7270/q23n27th

BindingDB Entry 50013092: Pleiotropic prodrugs: Design of a dual butyrylcholinesterase inhibitor and 5-HT

BindingDB (2022) · UC San Diego · doi:10.7270/q2kp85v3

BindingDB Entry 50007389: Multi-target-directed-ligands acting as enzyme inhibitors and receptor ligands.

BindingDB (2021) · UC San Diego · doi:10.7270/q2222z25

BindingDB Entry 50008501: 1-Benzylpyrrolidine-3-amine-based BuChE inhibitors with anti-aggregating, antioxidant and metal-chelating properties as multifunctional agents against Alzheimer's disease.

BindingDB (2021) · UC San Diego · doi:10.7270/q2639t4n

BindingDB Entry 50022156: Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with In Vitro and In Vivo Activity in Neurodegenerative Diseases.

BindingDB (2025) · UC San Diego · doi:10.7270/q2gb28qw

BindingDB Entry 50011917: Discovery of potent glycogen synthase kinase 3/cholinesterase inhibitors with neuroprotection as potential therapeutic agent for Alzheimer's disease.

BindingDB (2022) · UC San Diego · doi:10.7270/q20k2d6w

BindingDB Entry 50011815: Multifunctional 6-fluoro-3-[3-(pyrrolidin-1-yl)propyl]-1,2-benzoxazoles targeting behavioral and psychological symptoms of dementia (BPSD).

BindingDB (2022) · UC San Diego · doi:10.7270/q2gx4g68

BindingDB Entry 50001162: Isosteroidal alkaloids as potent dual-binding site inhibitors of both acetylcholinesterase and butyrylcholinesterase from the bulbs of Fritillaria walujewii.

BindingDB (2020) · UC San Diego · doi:10.7270/q20k2c34

BindingDB Entry 50012304: A dual-acting 5-HT

BindingDB (2022) · UC San Diego · doi:10.7270/q2zc86k7

Novel Multitarget-Directed Ligands Aiming at Symptoms and Causes of Alzheimer’s Disease

Więckowska, A., Wichur, T., Godyń, J., Bucki, A., Marcinkowska, M., Siwek, A., Więckowski, K., Zaręba, P., Knez, D., Głuch‐Lutwin, M., et al. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00024 · Cited by 54 · see citing works

Pleiotropic prodrugs: Design of a dual butyrylcholinesterase inhibitor and 5-HT6 receptor antagonist with therapeutic interest in Alzheimer's disease.

Toublet, F.-X., Lalut, J., Hatat, B., Lecoutey, C., Davis, A., Since, M., Corvaisier, S., Freret, T., Santos, J. S.-D. O., Claeysen, S., et al. (2020) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2020.113059 · Cited by 31 · see citing works

A Novel in vivo Anti-amnesic Agent, Specially Designed to Express Both Acetylcholinesterase (AChE) Inhibitory, Serotonergic Subtype 4 Receptor (5-HT4R) Agonist and Serotonergic Subtype 6 Receptor (5-HT6R) Inverse Agonist Activities, With a Potential Interest Against Alzheimer’s Disease

Hatat, B., Yahiaoui, S., Lecoutey, C., Davis, A., Fréret, T., Boulouard, M., Claeysen, S., Rochais, C., & Dallemagne, P. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00148 · Cited by 34 · see citing works

Novel multitarget-directed ligands targeting acetylcholinesterase and σ1 receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase

Lalut, J., Santoni, G., Karila, D., Lecoutey, C., Davis, A., Nachon, F., Silman, I., Sussman, J. L., Weik, M., Maurice, T., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.10.064 · Cited by 52 · see citing works

Discovery of 1-(phenylsulfonyl)-1H-indole-based multifunctional ligands targeting cholinesterases and 5-HT6 receptor with anti-aggregation properties against amyloid-beta and tau

Wichur, T., Pasieka, A., Godyń, J., Panek, D., Góral, I., Latacz, G., Honkisz-Orzechowska, E., Bucki, A., Siwek, A., Głuch‐Lutwin, M., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113783 · Cited by 27 · see citing works