Synthesis and Evaluation of Novel Xanthone Derivatives as Potent AChE Inhibitors

Falin Qu; Guojing Bai; Wenshen Dong; Yan Yang; Yongsheng Jin; Qingguo Meng; Qiuye Wu; Wei Guo; Shichong Yu

doi:10.14233/ajchem.2014.16096

Issue

Vol. 26 No. 12 (2014): Vol 26 Issue 12

Issue Published : June 5, 2014

This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis and Evaluation of Novel Xanthone Derivatives as Potent AChE Inhibitors

https://doi.org/10.14233/ajchem.2014.16096

Falin Qu

102 Hospital of Chinese People's Liberation Army, 20 Heping North Road, Changzhou 213001, P.R. China;These two authors contributed equally to this work.

Guojing Bai

Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P.R. China; College of Pharmacy, Yantai University, 30 Qingquan Road, Yantai 264005, P.R. China; These two authors contributed equally to this work.

Wenshen Dong

102 Hospital of Chinese People's Liberation Army, 20 Heping North Road, Changzhou 213001, P.R. China

Yan Yang

Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P.R. China

Yongsheng Jin

Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P.R. China

Qingguo Meng

College of Pharmacy, Yantai University, 30 Qingquan Road, Yantai 264005, P.R. China

Qiuye Wu

Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P.R. China

Wei Guo

102 Hospital of Chinese People's Liberation Army, 20 Heping North Road, Changzhou 213001, P.R. China

Shichong Yu

Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P.R. China

Corresponding Author(s) : Wei Guo

yuscc@hotmail.com; ysjin@smmu.edu.cn

Asian Journal of Chemistry, Vol. 26 No. 12 (2014): Vol 26 Issue 12
Article Published : June 5, 2014

Abstract

A new series of xanthone derivatives have been designed, synthesized and evaluated as potent AChE inhibitors. Some of them showed more potent inhibitory activities to AChE than galanthamine. The most potent inhibitor xanthone derivative 2a inhibit AChE with a IC₅₀ of 0.57 μM and showed good AChE/BuChE inhibition selectivity. Molecular docking studies were also performed to understand the detail information of interaction between AChE and inhibitor.

Keywords

Xanthone Synthesis AChE Structure-activity relationship

Qu, F., Bai, G., Dong, W., Yang, Y., Jin, Y., Meng, Q., … Yu, S. (2014). Synthesis and Evaluation of Novel Xanthone Derivatives as Potent AChE Inhibitors. Asian Journal of Chemistry, 26(12), 3496–3498. https://doi.org/10.14233/ajchem.2014.16096

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References

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Representative analytical data for compound 2a, yield 72 %, 1HNMR (300 MHz, DMSO-d6, TMS): δ 10.41 (1 H, br, NH), 8.25 (1 H, s, Ar), 7,96 (1 H, br, Ar), 7.48 (1 H, d, Ar), 6.66 (1 H, s, Ar), 6.49 (1 H, s, Ar), 3.88 (3 H, s, OCH3), 3.83 (3 H, m, OCH3), 3.83 (2 H, br, CH2), 2.88-2.32 (6 H, m, CH2), 1.51-1.37 (6 H, m, CH2). ESI-MS, m/z: Calcd. 410.2, Found, 411.1 [M+H]+.
G.L. Ellman, K.D. Courtney, V.J. Andres Jr. and R.M. Featherstone, Biochem. Pharmacol., 7, 88 (1961); doi:10.1016/0006-2952(61)90145-9.
E.H. Rydberg, B. Brumshtein, H.M. Greenblatt, D.M. Wong, D. Shaya, L.D. Williams, P.R. Carlier, Y.P. Pang, I. Silman and J.L. Sussman, J. Med. Chem., 49, 5491 (2006); doi:10.1021/jm060164b.

References

V.N. Talesa, Mech. Ageing Dev., 122, 1961 (2001); doi:10.1016/S0047-6374(01)00309-8.

P. Camps, X. Formosa, C. Galdeano, T. Gómez, D. Munoz-Torrero, M. Scarpellini, E. Viayna, A. Badia, M.V. Clos, A. Camins, M. Pallàs, M. Bartolini, F. Mancini, V. Andrisano, J. Estelrich, M. Lizondo, A. Bidon-Chanal and F. Luque, J. Med. Chem., 51, 3588 (2008); doi:10.1021/jm8001313.

S. Darvesh, D.A. Hopkins and C. Geula, Nat. Rev. Neurosci., 4, 131 (2003); doi:10.1038/nrn1035.

A. Rampa, A. Bisi, P. Valenti, M. Recanatini, A. Cavalli, V. Andrisano, V. Cavrini, L. Fin, A. Buriani and P. Giusti, J. Med. Chem., 41, 3976 (1998); doi:10.1021/jm9810046.

H. Tang, Y.B. Wei, C. Zhang, F.X. Ning, W. Qiao, S.L. Huang, L. Ma, Z.S. Huang and L.Q. Gu, Eur. J. Med. Chem., 44, 2523 (2009); doi:10.1016/j.ejmech.2009.01.021.

H. Hu, H. Liao, J. Zhang, W. Wu, J. Yan, Y. Yan, Q. Zhao, Y. Zou, X. Chai, S. Yu and Q. Wu, Bioorg. Med. Chem. Lett., 20, 3094 (2010); doi:10.1016/j.bmcl.2010.03.101.

H.G. Hu, M.J. Wang, Q.J. Zhao, H.L. Liao, L.Z. Cai, Y. Song, J. Zhang, S.C. Yu, W.S. Chen, C.M. Liu and Q.Y. Wu, Chem. Nat. Compd., 43, 663 (2007); doi:10.1007/s10600-007-0223-x.

H.G. Hu, M.J. Wang, Q.J. Zhao, S.C. Yu, C.M. Liu and Q.Y. Wu, Chin. Chem. Lett., 18, 1323 (2007); doi:10.1016/j.cclet.2007.09.011.

P.E. Eaton, G.R. Carlson and J.T. Lee, J. Org. Chem., 38, 4071 (1973); doi:10.1021/jo00987a028.

N.R. Ayyangar, K.C. Brahme, U.R. Kalkote and K.V. Srinivasan, Synthesis, 938 (1984); doi:10.1055/s-1984-31027.

Representative analytical data for compound 2a, yield 72 %, 1HNMR (300 MHz, DMSO-d6, TMS): δ 10.41 (1 H, br, NH), 8.25 (1 H, s, Ar), 7,96 (1 H, br, Ar), 7.48 (1 H, d, Ar), 6.66 (1 H, s, Ar), 6.49 (1 H, s, Ar), 3.88 (3 H, s, OCH3), 3.83 (3 H, m, OCH3), 3.83 (2 H, br, CH2), 2.88-2.32 (6 H, m, CH2), 1.51-1.37 (6 H, m, CH2). ESI-MS, m/z: Calcd. 410.2, Found, 411.1 [M+H]+.

G.L. Ellman, K.D. Courtney, V.J. Andres Jr. and R.M. Featherstone, Biochem. Pharmacol., 7, 88 (1961); doi:10.1016/0006-2952(61)90145-9.

E.H. Rydberg, B. Brumshtein, H.M. Greenblatt, D.M. Wong, D. Shaya, L.D. Williams, P.R. Carlier, Y.P. Pang, I. Silman and J.L. Sussman, J. Med. Chem., 49, 5491 (2006); doi:10.1021/jm060164b.

Issue

Vol. 26 No. 12 (2014): Vol 26 Issue 12

Synthesis and Evaluation of Novel Xanthone Derivatives as Potent AChE Inhibitors

Corresponding Author(s) : Wei Guo

Abstract

Keywords

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