Application of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors

Jianbo B. Tong, Yuan-Yuan Li, Guo-Yan Jang, kang-Nan Li

Abstract


In this work, a 3D-QSAR model involving for 40 dipeptidyl boronic acid proteasome inhibitors was built based on Topomer CoMFA, the multiple correlation coefficient of fitting, cross-validation and external validation were 0.908, 0.647 and 0.703, respectively. The results indicated that the obtained Topomer CoMFA model not only has favorable estimation stability but also good prediction capability. Topomer Searchwas employed as a tool for virtual screening in lead-like compounds of ZINC database. Finally, 1 R1 group, 7 R2 groups and 6 R3 groups with higher contribution values were employed to alternately substitute for the R1, R2 and R3 of template compound 23 with highest bioactivity. As a consequence, 33 new molecules with higher activity than that of template molecular were designed successfully. The results showed that the Topomer Search technology could be effectively apply to screen and design new dipeptidyl boronic acid proteasome inhibitors and has good predictive capability to design new dipeptidyl boronic acid proteasome inhibitors drugs as a guidance.


Keywords


quantitative structure–activity relationship (QSAR); proteasome inhibitors; Topomer CoMFA; Topomer search; design of new inhibitors

Full Text:

PDF (1,479 kB)

References


J. Adams, Nat. Rev. Cancer. 4 (2004) 349

T. Devine, M. S. Dai, Curr. Pharm. Des. 19 (2013) 3248

R. Z. Murray, C. Norbury, Anti-Cancer Drugs. 11 (2000) 407

A. Frankel, S. Man, P. Elliott, Clin. Cancer Res. 6 (2000) 3719

J. S. Wolf, Z. Chen, G. Dong, J. B. Sunwoo, C. C. Bancroft, D. E. Capo, N. T. Yeh, N. Mukaida, C. Van Waes, Clin. Cancer. Res. 7 (2001) 1812.

C. S. Mitsiades, N. Mitsiades, T. Hideshima, P. G. Richardson, K. C. Anderson, Curr. Drug Targets. 7 (2006) 1341

S. V. Rajkumar, P. G. Richardson, T. Hideshima, K. C. Anderson, J. Clin. Oncol. 23 (2005) 630

J. Shi, M. Lei, W. Wu, H. Feng, S. Chen, Bioorg. Med. Chem. Lett. 26 (2016) 1958

A. Hershko, A. Ciechanover, A. Varshavsky. Ann. Rev. Biochem. 67 (1998) 425

J. Prudhomme, E. Mcdaniel, N. Ponts, S. Bertani, W. Fenical, P. Jensen, K. L. Roch, Plos One 3 (2008) e2335

B. Skaug, X. Jiang, Z. J. Chen, Ann. Rev. Biochem. 78 (2009) 769

J. J. Chen, F. Lin, Z. H. Qin, Neurosci. Bulln. 24 (2008) 183

B. Dahlmann, BMC Biochem. 8 (2007) S3

J. J. Shah, R. Z. Orlowski, Expert Rev. Anticanc. 13 (2009) 1964

J. Zhang, P. Wu, Y. Hu, Curr. Med. Chem. 20 (2013) 2537

V. M. Dembitsky, A. A. Al Quntar, M. Srebnik, Chem. Rev. 111 (2011) 209

S. Touchet, F. Carreaux, B. Carboni, A. Bouillon, J. L. Boucher, Chem. Soc. Rev. 40 (2011) 3895

Y. Kong, K. Wang, M. C. Edler, E. Hamel, S. L. Mooberry, M. A. Paigea, M. L. Browna, Bioorgan. Med. Chem. 18 (2010) 971

R. D. Cramer, P. Cruz, G. Stahl, W. C. Curtiss, B. Campbell, B. B. Masek, F. Soltanshahi, J. Chem. Inf. Model. 48 (2008) 2180

R. D. Cramer, F. Soltanshahi, R. Jilek, B. Campbell, J. Comput.-Aided Mol. Des. 21 (2007) 341

M. Lei, H. Feng, C. Wang, H. Li, J. Wang, Z. Liu, S. Chen, S. Hu, Y. Zhu, Bioorgan. Med. Chem. 24 (2016) 2576

G. Melagraki, A. Afantitis, Rsc Adv. 4 (2014) 50713

M. Clark, R. D. Cramer, N. Van Opdenbosch, J. Comput. Chem. 10 (1989) 982

R. D. Cramer, D. E. Patterson, J. D. Bunce, J. Am. Chem. Soc. 110 (1988) 5959

A. Golbraikh, M. Shen, Z. Xiao, Y. D. Xiao, K. H. Lee, A. Tropsha, J. Comput.-Aided Mol. Des. 17 (2003) 241

S. Wold, Technometrics 20 (1978) 397

S. Wold, A. Ruhe, H. Wold, W. J. D. Iii, Siam J. Sci. Stat. Comp. 5 (1984) 735

L. Ståhle. S. Wold, J. Chemom. 1 (1987) 185

B. L. Bush, R. B. Nachbar, J. Comput.-Aided Mol. Des. 7 (1993), 587

P. P. Roy, J. T. Leonard, K. Roy, Chemom. Intell. Lab. Syst. 90 (2008) 31

J. J. Irwin, T. Sterling, M. M. Mysinger, E. S. Bolstad, R. G. Coleman, J. Chem. Inf. Model. 52 (2012) 1757.




DOI: http://dx.doi.org/10.2298/JSC161227047T

Refbacks



Copyright (c) 2017 J. Serb. Chem. Soc.

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

IMPACT FACTOR 0.822 (131 of 166 journals)
5 Year Impact Factor 1.015 (118 of 166 journals)