Ligand- and structure-based virtual screening of 16-((diiso-butylamino)methyl)-6α-hydroxyvouacapane-7β,17β-lactone, a compound with potential anti-prostate cancer activity

Rai Campos Silva, João Gabriel Curtolo Poiani, Ryan Silva Ramos, Josivan Silva Costa, Carlos H. T. Paula Silva, Davi do Socorro Barros Brasil, Cleydson Breno Rodrigues Santos

Abstract


Prostate cancer is one of the leading causes of disease and death on the planet. The probable bioactive pose of 16-((diisobutylamino)methyl)-
-6α-hydroxyvouacapane-7β,17β-lactone (N,N-DHL), a pivot compound with prostatic anti-cancer activity, was investigated via a semi-empirical method (PM3) and refined with the base set 6-31+G(d,p) calculated in the DFT method at the B3LYP level of theory. This structure was used in ligand-based virtual screening for five commercial compound bases using the software ROCS and EON that selected 2000 per base and another that resulted in 100 per base, respectively. This set was used for pharmacokinetic and toxicological predict­ions. The molecular overlap index at 50 % steric/electrostatic provided 68 structures that were used for a molecular docking study. The results showed that of 238,922 structures, only eight, 7 (–10.9 kcal mol-1) as the best in the series and 1 (–8.1 kcal mol-1) as less favorable, with others in this range (±2.8 kcal mol-1) with their respective binding affinity: 8 (–8.2 kcal mol-1), 5 (–8.2 kcal mol-1), 4 (–8.3 kcal mol-1), 2 (–8.5 kcal mol-1), 3 (–8.6 kcal mol-1) and 6 (–8.8 kcal mol-1) remaining in the final selection. The predictions for 21 pharmacokinetic properties were within the recommended range, similar to 95 % of the drugs available on the market, with no toxicity warning. The struc­tures showed similarity greater than 75 % to the pivot based on binding affinity and predictions but only the structures 6 and 7 were considered more promising for their potential anti-prostate cancer activity (PC-3).


Keywords


dihydrotestosterone; androgen receptor; DFT/6-31+G (d,p); virtual screening; derivative of vouacapane; drug design

References


T. C. A. Tonon, J. P. F. Schoffen, Rev. Saúde Pesqui 2 (2009) 403

I. N. C. A. Estimativa de incidência de Câncer no Brasil 2016/ Instituto Nacional de Câncer José Alencar Gomes da Silva, Coordenação de Prevenção e Vigilância, Brazil, 2017, http://www. inca. gov. br/estimativa/2016/ (Accessed June 18, 2017)

M. M. Center, A. Jemal, J. Lortet-Tieulent, E. Ward, J. Ferlay, O. Brawley, F. Bray, Eur. Urol. 61 (2012) 1079

R. Siegel, D. Naishadham, A. Jemal, Ca-Cancer J. Clin. 63 (2013) 11

R. L. Siegel, K. D. Miller, A. Jemal, Ca-Cancer J. Clin. 65 (2015) 05

D. M. Wilbert, J. E. Griffin, J. D. Wilson, J. Clin. Endocrinol. Metab. 56 (1983) 113

E. D. Crawford, J. Urol. 73 (2009) 4

J. C. Carvalho, J. A. Sertié, M. V. Barbosa, K. C. Patrício, L. R. Caputo, S. J. Sarti, L. P. Ferreira, J. K. Bastos, J. Ethnopharmacol. 64 (1999) 127

I. Carvalho, M. T. Pupo, A. D. L. Borges, L. S. Bernardes, Quím. Nova 26 (2003) 428

F. P. Euzébio, F. J. Dos Santos, D. Piló-Veloso, A. F. Alcântara, A. L. Ruiz, J. E. De Carvalho, M. A. Foglio, D. L. Ferreira-Alves, Â. De Fátima, Bioorg. Med. Chem. 18 (2010) 8172

P. Ripphausen, B. Nisius, J. Bajorath, Drug. Discov. Today 16 (2011) 372

N. Bruchovsky, P. S. Rennie, F. H. Batzold, S. L. Goldenberg, T. Fletcher, M. McLoughlin, J. Clin. Endocrinol. Metab. 67 (1988) 806

L. N. Thomas, R. C. Douglas, J. P. Vessey, R. Gupta, D. Fontaine, R. W. Norman, I. M. Thompson, D. A. Troyer, R. S. Rittmaster, C. B. Lazier, J. Urol. 170 (2003) 2019

O. A. A. Hamdi, E. H. Anouar, J. A. Shilpi, Z. B. K. A. Trabolsy, S. B. M. Zain, N. S. S. Zakaria, M. Zulkefeli, J. F. F. Weber, S. N. A. Malek, S. N. S. A. Rahman, K. Awang, Int. J. Mol. Sci. 16 (2015) 9450

ChemBridge, The Gold standard in small molecule screening libraries and building blocks, www.chembridge.com (Accessed Jun 22, 2017)

J. J. Irwin, B. K. Shoichet, J. Chem. Inf. Model. 45 (2005) 177

R. Dennington, T. Keith, J. Millam, GaussView, Version 5, Semichem Inc, Shawnee Mission, KS, 2009

Gaussian 03, Revision C.02, Gaussian, Inc., Wallingford, CA, 2004

Gaussian 98: revision A. 7, Gaussian, Inc., Pittsburgh PA, 1998

C. M. Breneman, K. B. Winberg, J. Comput. Chem. 11 (1990) 361

U. C. Singh, P. A. J. Kollman, J. Comput. Chem. 5 (1984) 129

P. C. D. Hawkins, A. Nicholls, J. Chem. Inf. Model. 52 (2012) 2919

Openeye Scientific Software. EON, version 2.0.1, Santa Fe, NM, 2007

Schrödinger Release 2019-1: QikProp, Schrödinger, LLC, New York, 2019

Schrödinger Release 2017-2: Maestro, Schrödinger, LLC, New York, 2017

T. Hou, J. Wang, Expert Opin. Drug Metab. Toxicol. 4 (2008) 759

N. S. R. Silva, D. J. L. Gonçalves, J. S. Silva, C. F. Santos, F. S. Braga, R. C. Silva, J. S. Costa, L. I. S. Hage-Melim, C. B. R. Santos, Comput. Mol. Biosci. 4 (2014) 47

C. A. Marchant, K. A. Briggs, A. Long, Toxicol. Mech. Methods 18 (2008) 177

N. Greene, P. N. Judson, J. J. Langowski, C. A. Marchant, SAR QSAR Environ. Res. 10 (1999) 299

DiscoveryStudio; INSIGHT, I. Accelrys Software Inc. San Diego, CA, 2009

H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, P. E. Bourne, Nucleic Acids Res. 28 (2000) 235

DS Viewer PRO 6.0. Accelrys, Inc., San Diego, CA, 2005

C. E. Bohl, Z. Wu, D. D. Miller, C. E. Bell, J. T. Dalton, J. Biol. Chem. 282 (2007) 13648

G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S. Goodsell, A. J. Olson, J. Comput. Chem. 30 (2009) 2785

S. Dallakyan, A. J. Olson, Methods Mol. Biol. 1263 (2015) 243

G. W. Turner, E. Tedesco, K. D. Harris, R. L. Johnston, B. M. Kariuki, Chem. Phys. Lett. 321 (2000) 183

W. L. Jorgensen, E. M. Duffy, ‎Adv. Drug Deliv. Rev. 54 (2002) 355

E. M. Duffy, W. L. Jorgensen, J. Am. Chem. Soc. 122 (2000) 2878

W. L. Jorgensen, E. M. Duffy, Bioorg. Med. Chem. Lett. 10 (2000) 1155

G. K. Zorzi, R. S. Schuh, A. M. D. Campos, E. L. Carvalho, M. B. Rott, H. F. Teixeira, Quím. Nova 40 (2017) 74

C. M. R. Sant'anna, Quím. Nova 25 (2002) 505

L. C. Tavares, Quim. Nova 27 (2004) 631

M. L. Connolly, J. Appl. Crystallogr. 16 (1983) 548

K. Palm, P. Stenberg, K. Luthman, P. Artursson, Pharm. Res. 14 (1997) 568

P. Ertl, B. Rohde, P. Selzer, J. Med. Chem. 43 (2000) 3714

J. D. Hughes, J. Blagg, D. A. Price, S. Bailey, G. A. Crescenzo, R. V. Devraj, E. Ellsworth, Y. M. Fobian, M. E. Gibbs, R. W. Gilles, N. Greene, E. Huang, T. Krieger-Burke, J. Loesel, T. Wager, L. Whiteley, Y. Zhang, Bioorg. Med. Chem. Lett. 18 (2008) 4872

H. Rojas, C. Ritter, F. D. Pizzol, Rev. Bras. Terap. Intens. 23 (2011) 222

J. Wang, T. Hou, Ann. Rep. Comput. Chem. 5 (2009) 101

X. Ma, C. Chen, J. Yang, Acta Pharmacol. Sin. 26 (2005) 500

S. Yamashita, T. Furubayashi, M. Kataoka, T. Sakane, H. Sezaki, H Tokuda, Eur. J. Pharm. Sci. 10 (2000) 195

K. Horie, F. Tang, R. T. Borchardt, Pharm. Res. 20 (2003) 161

P. Artursson, C. Magnusson, J. Pharm. Sci. 79 (1990) 595

W. Rubas, N. Jezyk, G. M. Grass, Pharm. Res. 10 (1993) 113

M. J. Ginski, R. Taneja, J. E. Polli, AAPS J. 1 (1999) 27

K. A. Lentz, J. Hayashi, L. J. Lucisano, J. E. Polli, Int.. J. Pharm. 200 (2000) 41

M. Kobayashi, N. Sada, M. Sugawara, K. Iseki, K. Miyazaki, Int. J. Pharm. 21 (2001) 87

S. Neulroff, A. L. Ungell, I. Zamora, P. Artusson, Eur. J. Pharm. Sci. 25 (2005) 211

J. De Souza, Z. M. F. Freitas, S. Storpirtis, Rev. Bras. Cienc. Farm. 43 (2007) 515

T. Fujita, J. Iwasa, C. Hansch, J. Am. Chem. Soc. 86 (1964) 5175

A. Leo, C. Hansch, D. Elkins, Chem. Rev. 71 (1971) 525

G. V. Betageri, J. A. Rogers, Int. J. Pharm. 36 (1987) 165

S. D. Krämer, Pharm. Sci. Technol. Today 2 (1999) 373

G. Jones, P. Willett, R. C. Glen, A. R. Leach, R. Taylor, J. Mol. Biol. 267 (1997) 727

U. Gowthaman, M. Jayakanthan, D. Sundar, BMC Bioinf. 9 (2008) S14

K. E. Hevener, W. Zhao, D. M. Ball, K. Babaoglu, J. Qi, S. W. White, R. E. Lee, J. Chem. Inf. Model. 49 (2009) 444

T. C. Lima, R. Lucarini, A. C. Volpe, C. Q. Andrade, A. M. Souza, P. M. Pauletti, A. H. Januário, G. V. Símaro, J. K. Bastos, W. R. Cunha, A. Borges, R. S. Laurentiz, V. A. Conforti, R. L. T. Parreira, C. H. G. Borges, G. F. Caramori, K. F. Andriani, M. L. A. Silva, Bioorg. Med. Chem. Lett. 27 (2017) 176

C. Biot, E. Buisine, J. M. Kwasigroch, R. Wintjens, J. Biol. Chem. 277 (2002) 40816

J. P. Gallivan, D. A. Dougherty, Proc. Nat. Acad. Sci. U.S.A. 96 (1999) 9459

J. M. Berg, J. L. Tymoczko, L. Stryer, Biochemistry, 5th ed., section 1.3, Chemical Bonds in Biochemistry, W. H. Freeman, New York, 2002, https://www.ncbi.nlm.nih.gov/

/books/NBK22567/ (Accessed Dec 19, 2016).




DOI: https://doi.org/10.2298/JSC180129047S

Copyright (c) 2018 J. Serb. Chem. Soc.

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

IMPACT FACTOR 0.797 (139 of 171 journals)
5 Year Impact Factor 0.923 (134 of 171 journals)