Design, Synthesis, and Evaluation of Orally Bioavailable Quinoline–Indole Derivatives as Innovative Multitarget-Directed Ligands: Promotion of Cell Proliferation in the Adult Murine Hippocampus for the Treatment of Alzheimer’s Disease
Abstract
A novel series of quinoline-indole derivatives were synthesized and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease (AD). Biological evaluation revealed that the derivatives had multifunctional profiles including antioxidant effects, blood-brain barrier (BBB) penetration, biometal chelation, Aβ aggregation modulation, neurotrophic and neuroprotective properties. Moreover, several representative target derivatives demonstrated hippocampal cell proliferation in living adult mice by intracerebroventricular (icv) injection or oral administration. Further drug-like property analysis demonstrated that the optimized compound, 8d (WI-1758), had liver microsomal metabolic stability, was well tolerated (>2000 mg/kg), and had a rational pharmacokinetic profile, as well as an oral bioavailability of 14.1% and a positive log BB (-0.19) to cross the BBB in vivo. Pharmacodynamics studies demonstrated that chronic oral administration of 8d·HCl substantially ameliorated the cognitive and spatial memory deficits in APP/PS1 AD mice and noticeably reduced overall cerebral β-amyloid deposits.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Indole-based melatonin-N-benzylamine hybrids promote the development of neural stem cells into neuronal phenotypes.
“Interestingly, among those small molecules, indole-based melatonin-N-benzylamine hybrids, have been proven to effectively promote the development of neural stem cells into neuronal phenotypes.128”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [128]
Cites
1 retracted
Ranković, Z. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01469 · Cited by 94 · see citing works
RetractedAlzheimer’s disease: Clinical trials and drug development
Mangialasche, F., Solomon, A., Winblad, B., Mecocci, P., & Kivipelto, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70119-8 · Cited by 1,217 · see citing works
High throughput artificial membrane permeability assay for blood–brain barrier
Di, L., Kerns, E. H., Fan, K., McConnell, O. J., & Carter, G. T. (2003) · European Journal of Medicinal Chemistry · doi:10.1016/s0223-5234(03)00012-6 · Cited by 1,195 · see citing works
(2016) · London School of Economics and Political Science Research Online (London School of Economics and Political Science) · Cited by 874 · see citing works
Adlard, P. A., Cherny, R. A., Finkelstein, D. I., Gautier, E., Robb, E., Cortes, M., Volitakis, I., Liu, X., Smith, J. P., Perez, K., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.018 · Cited by 672 · see citing works
Fluoxetine targets early progenitor cells in the adult brain
Encinas, J. M., Vaahtokari, A., & Enikolopov, G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601992103 · Cited by 637 · see citing works
CNS Drug Design: Balancing Physicochemical Properties for Optimal Brain Exposure
Ranković, Z. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm501535r · Cited by 582 · see citing works
A regenerative approach to the treatment of multiple sclerosis
Deshmukh, V. A., Tardif, V., Lyssiotis, C. A., Green, C. C., Kerman, B., Kim, H. J., Padmanabhan, K., Swoboda, J. G., Ahmad, I., Kondo, T., et al. (2013) · Nature · doi:10.1038/nature12647 · Cited by 522 · see citing works
Biological metals and metal-targeting compounds in major neurodegenerative diseases
Barnham, K. J., & Bush, A. I. (2014) · Chem. Soc. Rev. · doi:10.1039/c4cs00138a · Cited by 497 · see citing works
Wohnsland, F., & Faller, B. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm001020e · Cited by 496 · see citing works
PBT2 Rapidly Improves Cognition in Alzheimer's Disease: Additional Phase II Analyses
Faux, N. G., Ritchie, C. W., Gunn, A. P., Rembach, A., Tsatsanis, A., Bedő, J., Harrison, J., Lannfelt, L., Blennow, K., Zetterberg, H., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1390 · Cited by 406 · see citing works
Discovery of a Proneurogenic, Neuroprotective Chemical
Pieper, A. A., Xie, S., Capota, E., Estill, S. J., Zhong, J., Long, J. M., Becker, G. L., Huntington, P. J., Goldman, S. E., Shen, C.-H., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.018 · Cited by 350 · see citing works
Zheng, H., Weiner, L. M., Bar-Am, O., Epsztejn, S., Cabantchik, Z. I., Warshawsky, A., Youdim, M. B. H., & Fridkin, M. (2005) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2004.10.037 · Cited by 278 · see citing works
Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease
Wang, J. M., Singh, C., Liu, L., Irwin, R. W., Chen, S., Chung, E. J., Thompson, R. F., & Brinton, R. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001422107 · Cited by 263 · see citing works
Rodrı́guez-Franco, M. I., Fernández‐Bachiller, M. I., Pérez, C., Hernández‐Ledesma, B., & Bartolomé, B. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050746d · Cited by 250 · see citing works
P7C3 Neuroprotective Chemicals Function by Activating the Rate-Limiting Enzyme in NAD Salvage
Wang, G., Han, T., Nijhawan, D., Theodoropoulos, P., Naidoo, J., Yadavalli, S., Mirzaei, H., Pieper, A. A., Ready, J. M., & McKnight, S. L. (2014) · Cell · doi:10.1016/j.cell.2014.07.040 · Cited by 243 · see citing works
Melatonin Modulates Cell Survival of New Neurons in the Hippocampus of Adult Mice
Ramírez-Rodríguez, G. B., Klempin, F., Babu, H., Benítez‐King, G., & Kempermann, G. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.46 · Cited by 229 · see citing works
Robert, A., Liu, Y., Nguyen, M., & Meunier, B. (2015) · Accounts of Chemical Research · doi:10.1021/acs.accounts.5b00119 · Cited by 212 · see citing works
Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug
Marschallinger, J., Schäffner, I., Klein, B., Gelfert, R., Rivera, F. J., Illes, S., Grassner, L., Janssen, M., Rotheneichner, P., Schmuckermair, C., et al. (2015) · Nature Communications · doi:10.1038/ncomms9466 · Cited by 193 · see citing works
Rosini, M., Simoni, E., Bartolini, M., Cavalli, A., Ceccarini, L., Pascu, N., McClymont, D. W., Tarozzi, A., Bolognesi, M. L., Minarini, A., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm800577j · Cited by 186 · see citing works
Camps, P., Formosa, X., Galdeano, C., Muñoz‐Torrero, D., Ramírez, L., Gómez, E., Isambert, N., Lavilla, R., Badı́a, A., Clos, M. V., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900859q · Cited by 174 · see citing works
Savelieff, M. G., DeToma, A. S., Derrick, J. S., & Lim, M. H. (2014) · Accounts of Chemical Research · doi:10.1021/ar500152x · Cited by 174 · see citing works
Development of Proneurogenic, Neuroprotective Small Molecules
MacMillan, K. S., Naidoo, J., Liang, J., Melito, L. M., Williams, N. S., Morlock, L., Huntington, P. J., Estill, S. J., Longgood, J. C., Becker, G. L., et al. (2011) · Journal of the American Chemical Society · doi:10.1021/ja108211m · Cited by 170 · see citing works
Viayna, E., Sola, I., Bartolini, M., Simone, A. D., Tapia‐Rojas, C., Serrano, F. G., Sabaté, R., Juárez‐Jiménez, J., Pérez, B., Luque, F. J., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401824w · Cited by 156 · see citing works
Teo, J.-L., Ma, H., Nguyen, C., Lam, C., & Kahn, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504600102 · Cited by 151 · see citing works
Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of Parkinson disease
Jesús‐Cortés, H. D., Xu, P., Drawbridge, J., Estill, S. J., Huntington, P. J., Tran, S., Britt, J. K., Tesla, R., Morlock, L., Naidoo, J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213956109 · Cited by 130 · see citing works
Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis
Tesla, R., Wolf, H. P., Xu, P., Drawbridge, J., Estill, S. J., Huntington, P., McDaniel, L., Knobbe, W., Burket, A., Tran, S., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213960109 · Cited by 129 · see citing works
Wang, Z., Wang, Y., Wang, B., Li, W., Huang, L., & Li, X. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01222 · Cited by 120 · see citing works
Self-citationAmiri, H., Saeidi, K., Borhani, P., Manafirad, A., Ghavami, M., & Zerbi, V. (2013) · ACS Chemical Neuroscience · doi:10.1021/cn4001582 · Cited by 114 · see citing works
Yu, C., Chang, P., Hsin, L., & Chern, J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400564j · Cited by 106 · see citing works
Farina, R., Pisani, L., Catto, M., Nicolotti, O., Gadaleta, D., Denora, N., Soto‐Otero, R., Méndez‐Álvarez, E., Passos, C. D. S., Muncipinto, G., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00599 · Cited by 100 · see citing works
P7C3 and an unbiased approach to drug discovery for neurodegenerative diseases
Pieper, A. A., McKnight, S. L., & Ready, J. M. (2014) · Chemical Society Reviews · doi:10.1039/c3cs60448a · Cited by 99 · see citing works
Multi-target-directed phenol–triazole ligands as therapeutic agents for Alzheimer's disease
Jones, M. R., Mathieu, É., Dyrager, C., Faissner, S., Vaillancourt, Z., Korshavn, K. J., Lim, M. H., Ramamoorthy, A., Yong, V. W., Tsutsui, S., et al. (2017) · Chemical Science · doi:10.1039/c7sc01269a · Cited by 96 · see citing works
Decker, M. W., Kraus, B., & Heilmann, J. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.02.083 · Cited by 94 · see citing works
López-Iglesias, B., Pérez, C., Morales-Garcia, J. A., Alonso‐Gil, S., Pérez‐Castillo, A., Romero, A., López, M. G., Villarroya, M., Conde, S., & Rodrı́guez-Franco, M. I. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5000613 · Cited by 90 · see citing works
Discovery of a Phosphodiesterase 9A Inhibitor as a Potential Hypoglycemic Agent
Shao, Y., Huang, M., Cui, W., Feng, L.-J., Wu, Y., Cai, Y.-H., Li, Z., Zhu, X., Liu, P., Wan, Y., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500836h · Cited by 74 · see citing works
Naidoo, J., Jesús‐Cortés, H. D., Huntington, P. J., Estill, S. J., Morlock, L., Starwalt, R., Mangano, T. J., Williams, N. S., Pieper, A. A., & Ready, J. M. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401919s · Cited by 73 · see citing works
Beck, M. W., Oh, S. B., Kerr, R. A., Lee, H. J., Kim, S., Kim, S., Jang, M., Ruotolo, B. T., Lee, J., & Lim, M. H. (2015) · Chemical Science · doi:10.1039/c4sc03239j · Cited by 71 · see citing works
Derrick, J. S., Kerr, R. A., Nam, Y., Oh, S. B., Lee, H. J., Earnest, K. G., Suh, N., Peck, K. L., Özbil, M., Korshavn, K. J., et al. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b10043 · Cited by 70 · see citing works
Sola, I., Aso, E., Frattini, D., López‐González, I., Espargaró, A., Sabaté, R., Pietro, O. D., Luque, F. J., Clos, M. V., Ferrer, I., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00624 · Cited by 66 · see citing works
DeToma, A. S., Krishnamoorthy, J., Nam, Y., Lee, H. J., Brender, J., Kochi, A., Lee, D., Onnis, V., Congiu, C., Manfredini, S., et al. (2014) · Chemical Science · doi:10.1039/c4sc01531b · Cited by 58 · see citing works
Liew, K.-F., Chan, K., & Lee, C. Y. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.02.055 · Cited by 54 · see citing works
Brunschweiger, A., Iqbal, J., Umbach, F., Scheiff, A. B., Munkonda, M. N., Sévigny, J., Knowles, A. F., & Müller, C. E. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm800175e · Cited by 52 · see citing works
Stemistry: the control of stem cells in situ using chemistry.
Davies, S., Kennewell, P., Russell, A., Seden, P. T., Westwood, R., & Wynne, G. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm500838d · Cited by 31 · see citing works
Mujika, J. I., Rodrı́guez-Guerra, J., López, X., Ugalde, J. M., Rodrı́guez-Santiago, L., Sodupe, M., & Maréchal, J. (2017) · Chemical Science · doi:10.1039/c7sc01296a · Cited by 22 · see citing works
Wang, Z., Wang, Y., Li, W., Liu, Z., Luo, Z., Sun, Y., Wu, R., Huang, L., & Li, X. (2015) · Dalton Transactions · doi:10.1039/c5dt02130h · Cited by 19 · see citing works
Self-citationLambeng, N., Willaime‐Morawek, S., Mariani, J., Ruberg, M., & Brugg, B. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(02)00669-1 · Cited by 17 · see citing works
Porter, M. R., Kochi, A., Karty, J. A., Lim, M. H., & Zaleski, J. M. (2014) · Chemical Science · doi:10.1039/c4sc01979b · Cited by 16 · see citing works
Chang, P., Talekar, R. S., Kung, F., Chern, T., Huang, C., Ye, Q.-Q., Yang, M.-Y., Yu, C., Lai, S., Deore, R. R., et al. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.01.004 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Savelieff, M. G., Nam, G., Kang, J., Lee, H. J., Lee, M., & Lim, M. H. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00138 · Cited by 603 · see citing works
Quinoline and quinolone dimers and their biological activities: An overview
Chu, X., Wang, C., Liu, W., Liang, L., Gong, K., Zhao, C., & Sun, K. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.10.035 · Cited by 249 · see citing works
Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents
Millanao, A. R., Mora, A. Y., Villagra, N. A., Bucarey, S. A., & Hidalgo, A. A. (2021) · Molecules · doi:10.3390/molecules26237153 · Cited by 230 · see citing works
Multi-target design strategies for the improved treatment of Alzheimer's disease
Zhang, P., Xu, S., Zhu, Z., & Xu, J. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.020 · Cited by 218 · see citing works
Albertini, C., Salerno, A., de Sena Murteira Pinheiro, P., & Bolognesi, M. L. (2021) · Medicinal Research Reviews · doi:10.1002/med.21699 · Cited by 179 · see citing works
Insights of 8-hydroxyquinolines: A novel target in medicinal chemistry
Gupta, R., Luxami, V., & Paul, K. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.104633 · Cited by 159 · see citing works
Recent advances in the synthetic and medicinal perspective of quinolones: A review
Dhiman, P., Arora, N. R., Thanikachalam, P. V., & Monga, V. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.103291 · Cited by 153 · see citing works
Alzheimer's disease: Updated multi-targets therapeutics are in clinical and in progress
Sang, Z., Wang, K., Dong, J., & Tang, L. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114464 · Cited by 127 · see citing works
Multitarget Therapeutic Strategies for Alzheimer’s Disease: Review on Emerging Target Combinations
Maramai, S., Benchekroun, M., Gabr, M. T., & Yahiaoui, S. (2020) · BioMed Research International · doi:10.1155/2020/5120230 · Cited by 121 · see citing works
Sang, Z., Wang, K., Shi, J., Cheng, X., Zhu, G., Wei, R., Ma, Q., Yu, L., Zhao, Y., Tan, Z., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.111958 · Cited by 101 · see citing works
Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines
Saadeh, H. A., Sweidan, K., & Mubarak, M. S. (2020) · Molecules · doi:10.3390/molecules25184321 · Cited by 96 · see citing works
Sang, Z., Wang, K., Shi, J., Liu, W., Cheng, X., Zhu, G., Wang, Y., Zhao, Y., Qiao, Z., Wu, A., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112180 · Cited by 77 · see citing works
Sales, T. A., Prandi, I. G., de Castro, A. A., Leal, D. H. S., da Cunha, E. F. F., Kuča, K., & Ramalho, T. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081829 · Cited by 73 · see citing works
Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer’s Disease
Kim, N., & Lee, H. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147697 · Cited by 67 · see citing works
Cai, P., Fang, S., Yang, H., Yang, X., Liu, Q., Kong, L., & Wang, X. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.08.005 · Cited by 59 · see citing works
Self-citationKou, X., Song, L., Wang, Y., Yu, Q., Ju, H., Yang, A., & Shen, R. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.126927 · Cited by 59 · see citing works
Current Pharmaceutical Aspects of Synthetic Quinoline Derivatives
Tabassum, R., Ashfaq, M. H., & Oku, H. (2020) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557520999201214234735 · Cited by 53 · see citing works
Liu, Z., Zhang, B., Xia, S., Fang, L., & Gou, S.-H. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112997 · Cited by 48 · see citing works
Pérez-Areales, F. J., Turcu, A. L., Barniol‐Xicota, M., Pont, C., Pivetta, D., Espargaró, A., Bartolini, M., Simone, A. D., Andrisano, V., Pérez, B., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.07.051 · Cited by 43 · see citing works
Centrally Active Multitarget Anti-Alzheimer Agents Derived from the Antioxidant Lead CR-6
Pérez-Areales, F. J., Garrido, M., Aso, E., Bartolini, M., Simone, A. D., Espargaró, A., Ginex, T., Sabaté, R., Pérez, B., Andrisano, V., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00528 · Cited by 43 · see citing works
Wu, J., Kou, X., Ju, H., Zhang, H., Yang, A., & Shen, R. (2021) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2021.128316 · Cited by 42 · see citing works
Wang, D., Hu, M. S., Li, X., Zhang, D., Chen, C., Fu, J., Shao, S., Shi, G., Zhou, Y., Wu, S., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.02.053 · Cited by 41 · see citing works
Self-citationYan, J., Pang, Y., Zhuang, J., Lin, H., Zhang, Q., Han, L., Ke, P., Zhuang, J., & Huang, X. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00106 · Cited by 40 · see citing works
Zhou, L., Liang, Y.-F., Huang, Y., Yang, G., Zheng, L., Sun, J., Li, Y., Zhu, F., Qian, H., Wang, R., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113426 · Cited by 39 · see citing works
Chen, H., Mi, J., Li, S., Liu, Z., Yang, J. L., Chen, R., Wang, Y., Ban, Y., Zhou, Y. M., Dong, W., et al. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2023.2169682 · Cited by 36 · see citing works
Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design
Tanaka, M., Szatmári, I., & Vécsei, L. (2025) · Pharmaceuticals · doi:10.3390/ph18050607 · Cited by 35 · see citing works
Leuci, R., Brunetti, L., Laghezza, A., Loiodice, F., Tortorella, P., & Piemontese, L. (2020) · Applied Sciences · doi:10.3390/app10124118 · Cited by 35 · see citing works
Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy
Lachowicz, J. I., Lecca, L. I., Meloni, F., & Campagna, M. (2021) · Molecules · doi:10.3390/molecules26216639 · Cited by 34 · see citing works
Hu, J., Huang, Y.-D., Pan, T., Zhang, T., Su, T., Li, X., Luo, H., & Huang, L. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00376 · Cited by 33 · see citing works
Self-citationLiao, Q., Li, Q., Zhao, Y., Jiang, P. H., Yan, Y., Sun, H., Liu, W., Feng, F., & Qu, W. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.103844 · Cited by 33 · see citing works
Umar, M., Rehman, Y., Ambreen, S., Mumtaz, S. M., Shaququzzaman, M., Alam, M. M., & Ali, R. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102298 · Cited by 31 · see citing works
Discovery of novel butyrylcholinesterase inhibitors for treating Alzheimer's disease
Sang, Z., Huang, S., Tan, W., Ban, Y., Wang, K., Fan, Y., Chen, H., Zhang, Q., Liang, C., Mi, J., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.02.030 · Cited by 30 · see citing works
SAR studies of quinoline and derivatives as potential treatments for Alzheimer’s disease
Li, Z., Yin, L., Zhao, D., Jin, L., Sun, Y.-J., & Tan, C. (2022) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2022.104502 · Cited by 29 · see citing works
Zhou, Y., Lü, X., Yang, H., Chen, Y., Wang, F., Li, J., Tang, Z., Cheng, X.-F., Yang, Y., Xu, L., et al. (2019) · Molecules · doi:10.3390/molecules24234217 · Cited by 27 · see citing works
Mohasin, M., Alam, M. Z., Ullah, Q., Ahmad, A., Rahaman, P. F., & Khan, S. A. (2023) · Polycyclic aromatic compounds · doi:10.1080/10406638.2023.2270118 · Cited by 26 · see citing works
Alım, Z., Şirinzade, H., Kılınç, N., Dilek, E., & Süzen, S. (2024) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2024.138276 · Cited by 26 · see citing works
Huang, H., Bow, Y., Wang, C., Chen, Y., Fu, P.-R., Chang, K.-F., Wang, T.-W., Tseng, C.-H., Chen, Y., & Chiu, C. (2020) · Cancers · doi:10.3390/cancers12051348 · Cited by 26 · see citing works
Xu, H., & Li, T.-Z. (2022) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557522666220330123538 · Cited by 26 · see citing works
Hu, J., An, B., Pan, T., Li, Z., Huang, L., & Li, X. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2018.10.022 · Cited by 26 · see citing works
Self-citationBao, L., Liu, Y., Peng, J., Wang, Y., Dong, J., & Xu, X. (2021) · Organic Letters · doi:10.1021/acs.orglett.1c03693 · Cited by 25 · see citing works
Chen, Y., Wu, B., Hao, Y., Liu, Y., Zhang, Z., Tian, C., Ning, X., Guo, Y. Q., Liu, J., & Wang, X. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.03.044 · Cited by 21 · see citing works
Antioxidants in anti‐Alzheimer's disease drug discovery
Guo, J., Zhu, Y., Zhi, J., Lou, Q., Bai, R., & He, Y. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102707 · Cited by 20 · see citing works
Singh, G., Kumar, S., Panda, S. R., Kumar, P., Rai, S., Verma, H., Singh, Y. P., Kumar, S., Srikrishna, S., Naidu, V. G. M., et al. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00130 · Cited by 19 · see citing works
Hamuľaková, S., Kudlicková, Z., Janovec, L., Mezencev, R., Deckner, Z. J., Chernoff, Y. O., Janočková, J., Ihnatova, V., Bzonek, P., Novakova, N., et al. (2021) · Future Medicinal Chemistry · doi:10.4155/fmc-2020-0184 · Cited by 19 · see citing works
Pont, C., Ginex, T., Griñán-Ferré, C., Scheiner, M., Mattellone, A., Martínez, N., Arce, E., Soriano-Fernández, Y., Naldi, M., Simone, A. D., et al. (2021) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2021.113779 · Cited by 17 · see citing works
Tabassum, R., Ashfaq, M. H., Tahir, T., & Oku, H. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.134058 · Cited by 18 · see citing works
Nanotechnology‐empowered therapeutics targeting neurodegenerative diseases
Wang, Z., Gonzalez, K. M., Cordova, L. E., & Lu, J. (2023) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1907 · Cited by 18 · see citing works
Self-citationRecent Advancements in the Treatment of Alzheimer’s Disease: A Multitarget-directed Ligand Approach
Kumar, S., Mahajan, A. T., Ambatwar, R., & Khatik, G. L. (2023) · Current Medicinal Chemistry · doi:10.2174/0109298673264076230921065945 · Cited by 17 · see citing works
Tao, L., Wei, Y., & Shi, M. J. (2020) · Organic Chemistry Frontiers · doi:10.1039/d0qo00878h · Cited by 15 · see citing works
Farouki, K. E., Kacem, M., Dib, M., Ouchetto, H., Hafid, A., & Khouili, M. (2023) · Current Organocatalysis · doi:10.2174/0122133372264682231019101634 · Cited by 15 · see citing works
Discovery of a promising agent IQZ23 for the treatment of obesity and related metabolic disorders
Rao, Y., Zhao, X. D., Hu, Y., Li, C., Xu, Y., Song, Q., Yu, H., Song, B.-B., Chen, S.-B., Li, Q., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112172 · Cited by 15 · see citing works
Wang, Z., Cao, M., Xiang, H., Wang, W., Feng, X., & Yang, X. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00409 · Cited by 14 · see citing works
Self-citationSteroid–Quinoline Hybrids for Disruption and Reversion of Protein Aggregation Processes
Albuquerque, H. M. T., da Silva, R. N., Pereira, M., Maia, A. F., Guieu, S., Soares, A. R., Santos, C. M. M., Vieira, S. I., & Silva, A. M. S. (2022) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.1c00604 · Cited by 14 · see citing works
Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone
Kostopoulou, I., Tzani, A., Chronaki, K., Prousis, K. C., Pontiki, E. A., Hadjipavlou‐Litina, D., & Detsi, A. (2023) · Molecules · doi:10.3390/molecules29010190 · Cited by 12 · see citing works
Recent Advances in Transition Metal Free Synthetic Protocols for Quinoline Derivatives
Tabassum, R., Ashfaq, M. H., & Oku, H. (2020) · Current Organic Chemistry · doi:10.2174/1385272824999200616122557 · Cited by 12 · see citing works
Liu, Y., Cong, L., Han, C., Li, B., & Dai, R. (2020) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557520666201127104539 · Cited by 10 · see citing works
Shinde, A. D., Nandurkar, Y. M., Bhalekar, S., Walunj, Y., Ugale, S. R., Ahmad, I., Patel, H., Chavan, A., & Mhaske, P. C. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2217922 · Cited by 8 · see citing works
Fluorescent sterol probes for intracellular transport, imaging, and therapeutics
Mansuri, S., Mukherjee, T., & Kanvah, S. (2022) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2022.102222 · Cited by 7 · see citing works
Jing, L., Wei, W., Meng, B., Chantegreil, F., Nachon, F., Martı́nez, A., Wu, G., Zhao, H., Song, Y., Kang, D., et al. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106465 · Cited by 7 · see citing works
Effect of a newly synthesized quinoline-based compound (PPQ-8) on murine schistosomiasis mansoni
Taman, A. I., Alhusseiny, S. M., Saleh, N. E., Youssef, M., Mansour, B., Massoud, M. A. M., & El-Beshbishi, S. N. (2020) · Journal of Helminthology · doi:10.1017/s0022149x2000005x · Cited by 7 · see citing works
Mekheimer, R. A., Allam, S. M. R., Al‐Sheikh, M. A., Medrasi, H. Y., Abd‐Elmonem, M., & Sadek, K. U. (2025) · RSC Advances · doi:10.1039/d5ra00779h · Cited by 6 · see citing works
Shan, L., Li, H., Zheng, W., Wang, X., Wang, X., & Hu, Y. (2022) · Organic Letters · doi:10.1021/acs.orglett.2c03565 · Cited by 6 · see citing works
Wolfberry extracts inhibit Aβ1-42 aggregation and rescue memory loss of AD drosophila
Li, C., & Yang, J. (2019) · Food Science and Human Wellness · doi:10.1016/j.fshw.2019.12.007 · Cited by 6 · see citing works
Borisova, M. A., Ryabukhin, D. S., Ivanov, A. Y., Boyarskaya, I. А., Spiridonova, D. V., Kompanets, M. O., & Vasilyev, A. V. (2021) · Chemistry of Heterocyclic Compounds · doi:10.1007/s10593-021-03015-0 · Cited by 6 · see citing works
Fan, M., Song, X., Lu, L., He, J., Shen, Y., Zhang, C., Wang, F., & Xie, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116786 · Cited by 5 · see citing works
Skoptsova, A. A., Geronikaki, A. A., Novichikhina, N. P., Sulimov, A. V., Ilin, I. S., Sulimov, V. B., Bykov, G. A., Podoplelova, N. A., Pyankov, O. V., & Shikhaliev, K. S. (2024) · Molecules · doi:10.3390/molecules29020373 · Cited by 5 · see citing works
Wang, W., Pan, T., Su, R., Chen, M., Xiong, W., Xu, C., & Huang, L. (2024) · Frontiers in Chemistry · doi:10.3389/fchem.2024.1374930 · Cited by 5 · see citing works
Self-citationTabassum, R., Ashfaq, M. H., & Oku, H. (2020) · Journal of Heterocyclic Chemistry · doi:10.1002/jhet.4193 · Cited by 5 · see citing works
8-Hydroxyquinoline Derivatives as Drug Candidates for the Treatment of Alzheimer's Disease
Bartolomeu, P. F., Fortes, I. S., Zimmer, A. R., Lopes, M. S., & de Andrade, S. F. (2025) · Current Medicinal Chemistry · doi:10.2174/0109298673409645250823055140 · Cited by 4 · see citing works
Viveka, T. L., Angajala, G., Aruna, V., Nakka, M., & Aparna, Y. (2024) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2024.137482 · Cited by 4 · see citing works
Sharma, P., & Jha, N. S. (2023) · Journal of Molecular Recognition · doi:10.1002/jmr.3041 · Cited by 4 · see citing works
Vogt, A. G., de Oliveira, R. L., Voss, G. T., Blödorn, G. B., Alves, D. A. C., Wilhelm, E. A., & Luchese, C. (2022) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2022.173357 · Cited by 4 · see citing works
Yadav, M. B., & Jeong, Y. T. (2022) · Tetrahedron Letters · doi:10.1016/j.tetlet.2022.154158 · Cited by 4 · see citing works
Tabassum, R., Ashfaq, M. H., & Oku, H. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e05035 · Cited by 4 · see citing works
A turn on fluorescent probe for Zn2+ based on Quinoline with flexible chelating group
Zheng, D., Huang, R., & Lan, H. (2025) · Results in Chemistry · doi:10.1016/j.rechem.2025.102523 · Cited by 3 · see citing works
Recent Advances in the Quest for Treatment and Management of Alzheimer and Other Dementia
Tanwir, S. E., & Kumar, A. (2019) · Open Journal of Medicinal Chemistry · doi:10.4236/ojmc.2019.91001 · 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
Lü, X., Liu, Y., Qin, N., Yang, H., Qiao, Y., Jiang, X., Chen, Y., Feng, F., Liu, W., Zhou, Y., et al. (2021) · Future Medicinal Chemistry · doi:10.4155/fmc-2021-0039 · Cited by 3 · see citing works
Söderberg, B. C. G., & Berkowitz, W. F. (2022) · Organic reactions · doi:10.1002/0471264180.or111.02 · Cited by 3 · see citing works
Prachayasittikul, V., Pingaew, R., Prachayasittikul, S., & Prachayasittikul, V. (2022) · Heterocycles · doi:10.3987/rev-22-sr(r)6 · Cited by 2 · see citing works
Fathalla, E. M., El‐Faham, A., Soliman, S. M., Barakat, A., Haukka, M., Ramadan, S., Abu-Youssef, M. A. M., M.A.Badr, A., & Yousri, A. (2026) · Inorganica Chimica Acta · doi:10.1016/j.ica.2026.123269 · Cited by 1 · see citing works
Unveiling the pathogenesis and therapeutic strategies of Alzheimer’s disease through cuproptosis
Xu, S., Mu, J., Wang, Z., Yang, J., Tian, D., Shi, T., Lan, J., He, P., Hao, Z., Fu, Y., et al. (2026) · BioMetals · doi:10.1007/s10534-026-00835-5 · Cited by 1 · see citing works
Self-citationAlzheimer's disease therapeutics
Sang, Z., & Huang, L. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18611-0.00031-0 · Cited by 1 · see citing works
Self-citationBase-promoted tandem synthesis of 2-azaaryl indoline
Chen, S., Tan, J., Wu, H., Zhao, Q., & Shang, Y. (2023) · Organic & Biomolecular Chemistry · doi:10.1039/d3ob01444d
A Brief Review of the Medicinally Important Indole Derivatives
Dube, P. N., Chaudhari, S., Thakare, P. Y., Yadav, S., & Kore, Y. S. (2023) · Journal Of Advanced Zoology · doi:10.53555/jaz.v44is7.3027
Edukondalu, P., Ravi, N., Matta, R., Kishan, G., & Kumar, K. S. (2025) · Asian Journal of Organic Chemistry · doi:10.1002/ajoc.202400702
Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection
Singh, A. A., Arukha, A. P., & Song, M. (2026) · Molecules · doi:10.3390/molecules31132323
Manahelohe, G. M., Li, C.-S., Shi, C.-X., Chen, X., Li, F., Wang, Y., Hao, G., & Zhang, M. (2026) · Advanced Agrochem · doi:10.1016/j.aac.2026.09.003
Shanmugavel, B., & Vijayakumar, V. (2026) · Scientific Reports · doi:10.1038/s41598-026-65282-1
Piplani, M., Thakur, S., Kumar, P., Garg, S. S., Goyal, A., & Goyal, P. (2026) · Biomedical & Pharmacology Journal · doi:10.13005/bpj/3483
BindingDB (2023) · UC San Diego · doi:10.7270/q2fb56xk
BindingDB (2021) · UC San Diego · doi:10.7270/q2g1643k
BindingDB (2022) · UC San Diego · doi:10.7270/q23n2733
- Authors
- Wang, Z., Hu, J., Yang, X., Feng, X., Li, X., Huang, L., & Chan, A. S. C.
- Affiliations
- Sun Yat-sen University (CN)
- Hunan Normal University (CN)
- Corresponding author
- Li, Xingshu
- Huang, Ling
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-02-08
- Volume
- 61
- Issue
- 5
- Pages
- 1871-1894
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2786700855
- Cited by
- 91
- References
- 49
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 12 · 2022: 12 · 2021: 11 · 2020: 19 · 2019: 13 · 2018: 5
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education of the People's Republic of China (15ykpy04)
- National Natural Science Foundation of China (21302235, 21772241)
- Natural Science Foundation of Guangdong Province (2014A030313124)
- Guangzhou Municipality (201610010111)
- Government Province (2015TQ01R244)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Keywords
- multi-target-directed ligands, Alzheimer's disease, oral bioavailability, blood-brain barrier penetration, amyloid-beta aggregation, antioxidant activity, neuroprotection, neurotrophic activity, hippocampal cell proliferation, cognitive impairment, spatial memory, APP/PS1 mice, drug-likeness, pharmacokinetics, pharmacodynamics
- MeSH terms
- Alzheimer Disease, Animals, Blood-Brain Barrier, Hippocampus, Humans, Indoles, Ligands, Memory Disorders, Quinolines, Drug Design, Amyloid beta-Peptides, Cell Proliferation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review