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Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents.
J Enzyme Inhib Med Chem. 2016; 31(sup2):13-23.JE

Abstract

The aim of this study was to design new molecules and evaluate their anticholinesterase and amyloid beta (Aβ1-42) inhibition activities as multifunctional drug candidates for the treatment of Alzheimer's disease (AD). A series of 5,6-dimethoxy-1H-indene-2-carboxamides (1-22) was synthesized; cholinesterase inhibitory activities of the compounds were measured according to Ellman's colorimetric assay, while the thioflavin T assay was used for measuring the inhibition of Aβ1-42 aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds 20 and 21 were found to be the most potent BuChE inhibitors with respective IC50 values of 1.08 and 1.09 μM. Compounds 16, 20, 21 and 22 exhibited remarkable inhibition of Aβ1-42 aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor 20 displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound 20 may be an especially promising multifunctional drug for the prevention and treatment of AD.

Authors+Show Affiliations

a Department of Pharmaceutical Chemistry.a Department of Pharmaceutical Chemistry.b Department of Organic Chemistry , and.a Department of Pharmaceutical Chemistry.c Department of Pharmacognosy , Ataturk University , Erzurum , Turkey.b Department of Organic Chemistry , and.a Department of Pharmaceutical Chemistry.a Department of Pharmaceutical Chemistry.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27226239

Citation

Koca, Mehmet, et al. "Design, Synthesis and Biological Activity of 1H-indene-2-carboxamides as Multi-targeted anti-Alzheimer Agents." Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 31, no. sup2, 2016, pp. 13-23.
Koca M, Yerdelen KO, Anil B, et al. Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents. J Enzyme Inhib Med Chem. 2016;31(sup2):13-23.
Koca, M., Yerdelen, K. O., Anil, B., Kasap, Z., Sevindik, H., Ozyurek, I., Gunesacar, G., & Turkaydin, K. (2016). Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup2), 13-23.
Koca M, et al. Design, Synthesis and Biological Activity of 1H-indene-2-carboxamides as Multi-targeted anti-Alzheimer Agents. J Enzyme Inhib Med Chem. 2016;31(sup2):13-23. PubMed PMID: 27226239.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents. AU - Koca,Mehmet, AU - Yerdelen,Kadir Ozden, AU - Anil,Baris, AU - Kasap,Zeynep, AU - Sevindik,Handan, AU - Ozyurek,Ibrahim, AU - Gunesacar,Gulsen, AU - Turkaydin,Kubra, Y1 - 2016/05/26/ PY - 2016/5/27/pubmed PY - 2017/2/15/medline PY - 2016/5/27/entrez KW - AChE KW - Alzheimer KW - Aβ1–42 KW - BuChE KW - molecular modeling SP - 13 EP - 23 JF - Journal of enzyme inhibition and medicinal chemistry JO - J Enzyme Inhib Med Chem VL - 31 IS - sup2 N2 - The aim of this study was to design new molecules and evaluate their anticholinesterase and amyloid beta (Aβ1-42) inhibition activities as multifunctional drug candidates for the treatment of Alzheimer's disease (AD). A series of 5,6-dimethoxy-1H-indene-2-carboxamides (1-22) was synthesized; cholinesterase inhibitory activities of the compounds were measured according to Ellman's colorimetric assay, while the thioflavin T assay was used for measuring the inhibition of Aβ1-42 aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds 20 and 21 were found to be the most potent BuChE inhibitors with respective IC50 values of 1.08 and 1.09 μM. Compounds 16, 20, 21 and 22 exhibited remarkable inhibition of Aβ1-42 aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor 20 displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound 20 may be an especially promising multifunctional drug for the prevention and treatment of AD. SN - 1475-6374 UR - https://www.unboundmedicine.com/medline/citation/27226239/Design_synthesis_and_biological_activity_of_1H_indene_2_carboxamides_as_multi_targeted_anti_Alzheimer_agents_ L2 - https://www.tandfonline.com/doi/full/10.1080/14756366.2016.1186019 DB - PRIME DP - Unbound Medicine ER -