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Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation.
Bioorg Med Chem. 2011 Jan 15; 19(2):763-70.BM

Abstract

A new series of tacrine-multialkoxybenzene hybrids (9a-9n) were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced β-amyloid (Aβ) aggregation. All the synthesized compounds had high acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity with IC₅₀ values at the nanomolar range, which were much better than tacrine alone. A Lineweaver-Burk plot and molecular modeling study showed that these hybrids targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compounds 9a-9f with methylenedioxybenzene moiety showed higher self-induced Aβ aggregation inhibitory activity than a reference compound, curcumin. These compounds could be selected as multi-potent agents for further investigation to treat AD.

Authors+Show Affiliations

Sun Yat-sen University, Guangzhou, 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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21211982

Citation

Luo, Wen, et al. "Design, Synthesis and Evaluation of Novel Tacrine-multialkoxybenzene Hybrids as Dual Inhibitors for Cholinesterases and Amyloid Beta Aggregation." Bioorganic & Medicinal Chemistry, vol. 19, no. 2, 2011, pp. 763-70.
Luo W, Li YP, He Y, et al. Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation. Bioorg Med Chem. 2011;19(2):763-70.
Luo, W., Li, Y. P., He, Y., Huang, S. L., Tan, J. H., Ou, T. M., Li, D., Gu, L. Q., & Huang, Z. S. (2011). Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation. Bioorganic & Medicinal Chemistry, 19(2), 763-70. https://doi.org/10.1016/j.bmc.2010.12.022
Luo W, et al. Design, Synthesis and Evaluation of Novel Tacrine-multialkoxybenzene Hybrids as Dual Inhibitors for Cholinesterases and Amyloid Beta Aggregation. Bioorg Med Chem. 2011 Jan 15;19(2):763-70. PubMed PMID: 21211982.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation. AU - Luo,Wen, AU - Li,Yan-Ping, AU - He,Yan, AU - Huang,Shi-Liang, AU - Tan,Jia-Heng, AU - Ou,Tian-Miao, AU - Li,Ding, AU - Gu,Lian-Quan, AU - Huang,Zhi-Shu, Y1 - 2010/12/13/ PY - 2010/11/12/received PY - 2010/12/05/revised PY - 2010/12/06/accepted PY - 2011/1/8/entrez PY - 2011/1/8/pubmed PY - 2011/5/4/medline SP - 763 EP - 70 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 19 IS - 2 N2 - A new series of tacrine-multialkoxybenzene hybrids (9a-9n) were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced β-amyloid (Aβ) aggregation. All the synthesized compounds had high acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity with IC₅₀ values at the nanomolar range, which were much better than tacrine alone. A Lineweaver-Burk plot and molecular modeling study showed that these hybrids targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compounds 9a-9f with methylenedioxybenzene moiety showed higher self-induced Aβ aggregation inhibitory activity than a reference compound, curcumin. These compounds could be selected as multi-potent agents for further investigation to treat AD. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/21211982/Design_synthesis_and_evaluation_of_novel_tacrine_multialkoxybenzene_hybrids_as_dual_inhibitors_for_cholinesterases_and_amyloid_beta_aggregation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(10)01113-2 DB - PRIME DP - Unbound Medicine ER -