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Multifunctional tacrine-flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease.
Eur J Med Chem. 2013 Nov; 69:632-46.EJ

Abstract

A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-β (Aβ₁₋₄₂) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced Aβ₁₋₄₂ aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment.

Authors+Show Affiliations

State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24095756

Citation

Li, Su-Yi, et al. "Multifunctional Tacrine-flavonoid Hybrids With Cholinergic, Β-amyloid-reducing, and Metal Chelating Properties for the Treatment of Alzheimer's Disease." European Journal of Medicinal Chemistry, vol. 69, 2013, pp. 632-46.
Li SY, Wang XB, Xie SS, et al. Multifunctional tacrine-flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease. Eur J Med Chem. 2013;69:632-46.
Li, S. Y., Wang, X. B., Xie, S. S., Jiang, N., Wang, K. D., Yao, H. Q., Sun, H. B., & Kong, L. Y. (2013). Multifunctional tacrine-flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease. European Journal of Medicinal Chemistry, 69, 632-46. https://doi.org/10.1016/j.ejmech.2013.09.024
Li SY, et al. Multifunctional Tacrine-flavonoid Hybrids With Cholinergic, Β-amyloid-reducing, and Metal Chelating Properties for the Treatment of Alzheimer's Disease. Eur J Med Chem. 2013;69:632-46. PubMed PMID: 24095756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multifunctional tacrine-flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease. AU - Li,Su-Yi, AU - Wang,Xiao-Bing, AU - Xie,Sai-Sai, AU - Jiang,Neng, AU - Wang,Kelvin D G, AU - Yao,He-Quan, AU - Sun,Hong-Bin, AU - Kong,Ling-Yi, Y1 - 2013/09/21/ PY - 2013/04/26/received PY - 2013/09/05/revised PY - 2013/09/08/accepted PY - 2013/10/8/entrez PY - 2013/10/8/pubmed PY - 2014/7/9/medline KW - ASNDIIUXKSSGTR-UHFFFAOYSA-N KW - Alzheimer's disease KW - CCSIEQWILAQNOJ-UHFFFAOYSA-N KW - CFTXWMALZMFVFR-UHFFFAOYSA-N KW - Cholinesterase KW - DAQOTHBGIZARGM-UHFFFAOYSA-N KW - DDOHQRNJXWAFAL-UHFFFAOYSA-N KW - FYFPJPCNMIMCSI-UHFFFAOYSA-N KW - Flavonoid KW - JBVVLTRVHVGZEU-UHFFFAOYSA-N KW - JBXYRSPJNIZSAT-UHFFFAOYSA-N KW - JFGPPVAZTXRZDC-UHFFFAOYSA-N KW - JWCIYSMFMZTUME-UHFFFAOYSA-N KW - LESFBJPJZADQHL-UHFFFAOYSA-N KW - MDVLYACOLMKYAL-UHFFFAOYSA-N KW - Metal chelator KW - NHRHUIFWROFHGI-UHFFFAOYSA-N KW - NYSKQVVKHYVKTB-UHFFFAOYSA-N KW - OXTPOGAMUKLJIJ-UHFFFAOYSA-N KW - PDCBHYYTMYMYBE-UHFFFAOYSA-N KW - PGHRDQIVQWNEGD-UHFFFAOYSA-N KW - RQWXJZZQVBAPHB-UHFFFAOYSA-N KW - SXDGSJQISGFVLK-UHFFFAOYSA-N KW - TZWXGPOBAFCOHW-UHFFFAOYSA-N KW - Tacrine KW - VBAJECZQEAYMJO-UHFFFAOYSA-N KW - β-Amyloid aggregation SP - 632 EP - 46 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 69 N2 - A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-β (Aβ₁₋₄₂) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced Aβ₁₋₄₂ aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/24095756/Multifunctional_tacrine_flavonoid_hybrids_with_cholinergic_β_amyloid_reducing_and_metal_chelating_properties_for_the_treatment_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(13)00597-7 DB - PRIME DP - Unbound Medicine ER -