Pharmacophore modeling and 3D-QSAR studies of leucettines as potent Dyrk2 inhibitors

Medicinal Chemistry Research

Volumn 23, Issue 4, 2014, Pages 1925-1933

  Bahl, Anu ^a   Joshi, Prashant ^b   Bharate, Sandip B ^b   Chopra, Harish ^a  

^a SANT LONGOWAL INSTITUTE OF ENGINEERING AND TECHNOLOGY   (India)

^b CSIR INDIAN INSTITUTE OF INTEGRATIVE MEDICINE   (India)

Author keywords

Anti Alzheimer; Dyrk2; Leucettines; Partial least square analysis; Pharmacophore model; QSAR

Indexed keywords

DUAL SPECIFICITY TYROSINE PHOSPHORYLATED AND REGULATED KINASE 2 INHIBITOR; ENZYME INHIBITOR; LEUCETTINE; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CORRELATION COEFFICIENT; CRYSTAL STRUCTURE; ENZYME INHIBITION; HYDROGEN BOND; HYDROPHOBICITY; MOLECULAR MODEL; PHARMACOPHORE; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RECEPTOR BINDING; THREE DIMENSIONAL QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP;

EID: 84899026191     PISSN: 10542523     EISSN: 15548120     Source Type: Journal    
DOI: 10.1007/s00044-013-0767-1     Document Type: Article

References (21)

1. Bharate SB, Yadav RR, Battula S, Vishwakarma RA (2012a) Meridianins: marine-derived potent kinase inhibitors. Mini Rev Med Chem 12:618-631
2. Bharate SB, Manda S, Mupparapu N, Battini N, Vishwakarma RA (2012b) Chemistry and biology of fascaplysin, a potent marine-derived CDK-4 inhibitor. Mini Rev Med Chem 12:650-664
3. Bharate SB, Manda S, Joshi P, Singh B, Vishwakarma RA (2012c) Total synthesis and anti-cholinesterase activity of marine-derived bis-indole alkaloid fascaplysin. Med Chem Commun 3:1098-1103
4. Bharate SB, Yadav RR, Vishwakarma RA (2013a) QSAR and pharmacophore study of Dyrk1A inhibitory meridianin analogs as potential agents for treatment of neurodegenerative diseases. Med Chem 9:152-161
5. Bharate SB, Singh B, Bharate JB, Jain SK, Meena S, Vishwakarma RA (2013b) QSAR and pharmacophore modeling of N-acetyl-2- aminobenzothiazole class of phosphoinositide-3-kinase-alpha inhibitors. Med Chem Res 22:890-899
6. Cuny GD, Robin M, Ulyanova NP, Patnaik D, Pique V, Casano G, Liu J-F, Lin X, Xian J, Glicksman MA, Stein RL, Higgins JMG (2010) Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors. Bioorg Med Chem Lett 20:3491-3494
7. Cuny GD, Ulyanova NP, Patnaik D, Liu J-F, Lin X, Auerbach K, Ray SS, Xian J, Glicksman MA, Stein RL, Higgins JM (2012) Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors. Bioorg Med Chem Lett 22:2015-2019
8. Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P, Lozach O, Babault L, Tahtouh T, Baratte B, Ogawa Y, Hagiwara M, Eisenreich A, Rauch U, Knapp S, Meijer L, Bazureau JP (2011) Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem 54:4172-4186
9. Dixon SL, Smondyrev AM, Knoll EH, Rao SN, Shaw DE, Friesner RA (2006a) PHASE: a new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodology and preliminary results. J Comput Aided Mol Des 20:647-671 (Pubitemid 46023928)
10. Dixon SL, Smondyrev AM, Rao SN (2006b) PHASE: a novel approach to pharmacophore modeling and 3D database searching. Chem Biol Drug Des 67:370-372
11. Ferrer I, Barrachina M, Puig B, Lagran MMD, Marti E, Avila J, Dierssen M (2005) Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis 20:392-400 (Pubitemid 41476265)
12. Filippakopoulos P, Myrianthopoulos V, Kritsanida M, Magiatis P, Skaltsounis AL, Krojer T, Gileadi O, Hapka E, Fedorov O, Berridge G, Wang J, Shrestha L, Vollmar M, Von Delft F, Arrowsmith CH, Edwards A, Weigelt J, Bountra C, Mikros E, Knapp S (2010) Crystal structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (Dyrk2) in complex with an indirubin ligand. RCSB. doi:10.2210/pdb3kvw/pdb
13. Laguna A, Aranda S, Barallobre MJ, Barhoum R, Fernández E, Fotaki V, Delabar JM, de la Luna S, de la Villa P, Arbonés ML (2008) The protein kinase DYRK1A regulates caspase-9-mediated apotposis during retina development. Dev Cell 15:841-853
14. Lochhead PA, Sibbet G, Morrice N, Cleghon V (2005) Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell 121:925-936 (Pubitemid 40806423)
15. Maddika S, Chen J (2009) Protein kinase Dyrk2 is a scaffold that facilitates assembly of an E3 ligase. Nat Cell Biol 11:409-419
16. Miller CT, Aggarwal S, Lin TK, Dagenais SL, Contreras JI, Orringer MB, Glover TW, Beer DG, Lin L (2003) Amplification and overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2) gene in esophageal and lung adenocarcinomas. Cancer Res 63:4136-4143 (Pubitemid 36917938)
17. Park J, Song WJ, Chung KC (2009) Function and regulation of Dyrk1A: towards understanding Down syndrome. Cell Mol Life Sci 66:3235-3240
18. Tahtouh T, Elkins JM, Filippakopoulos P, Soundararajan M, Burgy G, Durieu E, Cochet C, Schmid RS, Lo DC, Delhommel F, Oberholzer AE, Pearl LH, Carreaux F, Bazureau JP, Knapp S, Meijer L (2012) Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B. J Med Chem 55:9312-9330
19. Taira N, Nihira K, Yamaguchi T, Miki Y, Yoshida K (2007) Dyrk2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage. Mol Cell 25:725-738 (Pubitemid 46341924)
20. Yamashita S, Chujo M, Moroga T, Anami K, Tokuishi K, Miyawaki M, Kawano Y, Takeno S, Yamamoto S, Kawahara K (2009) Dyrk2 expression may be a predictive marker for chemotherapy in non-small cell lung cancer. Anticancer Res 29:2753-2757
21. Yoshida K (2008) Role for Dyrk family kinases on regulation of apoptosis. Biochem Pharmacol 76:1389-1394