Molecular docking and pharmacophoric modelling of 1,5-disubstituted tetrazoles as inhibitors of two proteins present in cancer, the ABL and the mutated T315I kinase

Abstract

A docking study of a set of several 1,5-disubstituted tetrazoles compounds has been performed to predict the poses of some potential inhibitors of the Abelson tyrosine-protein kinase and the mutated Abelson tyrosine-protein kinase T315I. The study was conducted through Lamarckian genetic algorithms in Autodock4 package. Bayesian calculations were performed; specificity and sensitivity values as well as positive predicted values, and negative predicted values were calculated using a set of 99 known experimentally active ligands and 385 decoys for the Abelson tyrosine-protein kinase from the Directory of Useful Decoys database. Root mean square deviation values were calculated though the X-ray crystallographic data of the bioactive pose of imatinib as reference, and the pose obtained with the above methods. The obtained results show the importance of the protein interactions with the halogens present in some of these 1,5-disubstituted tetrazoles ligands, as well as the presence of some hydrophobic fragments, obtained via the pharmacophoric model, concluding that the eight novels 1,5-disubstituted tetrazoles compounds herein identified, could be effective inhibitors of Abelson tyrosine-protein kinase, using a docking calculations.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Scheme 1
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

References

  1. Abelson HT, Rabstein LS (1970) Lymphosarcoma: virus-induced thymic-independent disease in mice. Cancer Res 30:2213–2222 (Published August 1970)

    CAS  PubMed  Google Scholar 

  2. Auffinger P, Hays FA, Westhof E, Shing Ho P (2004) Halogen bonds in biological molecules. Proc Natl Acad Sci USA 101:16789–16794. https://doi.org/10.1073/pnas.0407607101

    CAS  Article  PubMed  Google Scholar 

  3. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Muller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Sabele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R (2013) European Leukemia Recommendations for the management of chronic myeloid leukemia. Blood 122:872–884. https://doi.org/10.1182/blood-2013-05-501569

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Ben-Neriah YQ, Daley G, Mes-Masson AN, Witte O, Baltimore D (1986) The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science 233:212–214. https://doi.org/10.1126/science.3460176

    CAS  Article  PubMed  Google Scholar 

  5. Capdeville R, Buchdunger E, Zimmermann J, Matter A (2002) Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 1:403–502. https://doi.org/10.1038/nrd839

    CAS  Article  Google Scholar 

  6. Casewit CJ, Colwell KS, Rappé AK (1992) Application of a universal force field to organic molecules. J Am Chem Soc 114:10035–10046. https://doi.org/10.1021/ja00051a041

    CAS  Article  Google Scholar 

  7. Cavallo G, Metrangolo P, Milani R, Pilati T, Priimagi A, Resnati G, Terraneo G (2016) The halogen bond. Chem Rev 116:2478–2601. https://doi.org/acs.chemrev.5b00484

  8. Colicelli J (2011) ABL tyrosine kinases: evolution of function, regulation, and specificity. Science Signal 3:139 re6. https://doi.org/10.1126/scisignal.3139re6

  9. Cortes-García CJ, Jácome A, Rentería A, Gámez R (2016) Synthesis of 1,5-disubstituted tetrazoles containing a fragment of the anticancer drug imatinib via a microwave-assisted Ugi-azide reaction. Monat Chem 147:1277–1290. https://doi.org/10.1007/s0070

    Article  Google Scholar 

  10. Cousins KR (2011) Computer review of ChemDraw ultra 12.0. J Am Chem Soc 133:8388. https://doi.org/10.1021/ja204075s

    CAS  Article  PubMed  Google Scholar 

  11. Cowan-Jacob SW, Fendrich G, Floersheimer A, Furet P, Liebetanz J, Rummel G, Rheinberger P, Centeleghe M, Fabbro D, Manley PW (2007) Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia. Biol Cryst 63:80–93. https://doi.org/10.1107/S0907444906047287

    CAS  Article  Google Scholar 

  12. Desogus A, Schenone S, Brullo C, Tintori C, Musumeci F (2015) Bcr-Abl tyrosine kinase inhibitors: a patent review. Exp Opin Ther Pat 25:1–16. https://doi.org/10.1517/13543776.2015.11012155

    Article  Google Scholar 

  13. Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ (2016) Computational protein–ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc 11:905–919. https://doi.org/10.1038/nprot.2016.051

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng GJL, Hada M, Ehara MKR, Fukuda J, Hasegawa M, Ishida T, Nakajima Y, Honda O, Kitao H, Nakai T Vreven JA, Montgomery Jr. JE, Peralta F, Ogliaro M, Bearpark JJ, Heyd E, Brothers KN, Kudin VN, Staroverov R, Kobayashi J, Normand K, Raghavachari A, Rendell JC, Burant SS, Iyengar J, Tomasi M, Cossi N, Rega JM, Millam M, Klene JE, Knox JB, Cross V, Bakken C, Adamo J, Jaramillo R, Gomperts RE, Stratmann O, Yazyev AJ, Austin R, Cammi C, Pomelli JW, Ochterski RL, Martin K, Morokuma VG, Zakrzewski GA, Voth P Salvador JJ, Dannenberg S, Dapprich AD, Daniels Ö, Farkas JB, Foresman JV, Ortiz J, Cioslowski, Fox DJ (2009) Gaussian 09, revision E.01. Gaussian, Inc., Wallingford

  15. Gallardo S, Ocampo AL, Contreras CA, Chacón L (2014) Synthesis and docking studies of the novel N-(2,2-di(1H-pyrrol-2-yl)ethyl)adamantane-1-carboxamide, a potential 11β-HSD1 inhibitor. J Chem Hindawi. https://doi.org/10.1155/2014/294246

    Article  Google Scholar 

  16. Ghaaliq A, McCluskey A (2008) Clinical tests: sensitivity and specificity. Continuing education in anaesthesia. Criti Care Pain 8:221–223. https://doi.org/10.1093/bjaceaccp/mkn041

    Article  Google Scholar 

  17. Hantschel O, Superti-Furga G (2004) Regulation of the C-ABL and BCR-ABL tyrosine kinases. Nat Rev Mol Cell Biol 5:33–44. https://doi.org/10.1038/nrm1280

    CAS  Article  Google Scholar 

  18. Huang N, Schoichet BK, Irwing JJ (2006) Benchmarking sets for molecular docking. J Med Chem 49:6789–6801. https://doi.org/10.1021/jm0608356

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Iwari A, Panigrahi SK (2007) HBAT: a complete package for analysing strong and weak hydrogen bonds in macromolecular crystal structures. In Silico Biol 6:651–661. https://content.iospress.com/articles/insilico-biology/isb00337

  20. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Neiderwieser D, Resta D, Capdeville R, Zoellner U, Talpaz M, Druker B (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346:645–652. https://doi.org/10.1056/NEJMoa011573

    CAS  Article  PubMed  Google Scholar 

  21. Kaplan W, Littlejohn TG (2001) Swiss-PDB viewer (deep view). Brief Bioinform 2:195–197. https://doi.org/10.1093/bib/2.2.195

    CAS  Article  PubMed  Google Scholar 

  22. Koebel MR, Schmadeke G, Posner RG, Sirimulla S (2016) AutoDock VinaXB: implementation of XBSF, new empirical halogen bond scoring function, into AutoDock Vina. J Cheminform. https://doi.org/10.1186/s13321-016-0139-1

    Article  PubMed  PubMed Central  Google Scholar 

  23. Koes, Camacho CJ (2012) ZINCPharmer: pharmacophore search of the ZINC database. Nucl Acid Res 40:W409–W414. https://doi.org/10.1093/nar/gks378

    CAS  Article  Google Scholar 

  24. Kortagere S, Ekins S, Welsh WJ (2008) Halogenated ligands and their interactions with amino acids: implications for structure-activity and structure-toxicity relationships. J Mol Graph Model 27:170–177. https://doi.org/10.1016/j.jmgm.2008.04001

    CAS  Article  PubMed  Google Scholar 

  25. Kumar H, Raj U, Gupta S, Tripathi R, Kumar P (2015) Systemic review on chronic myeloid leukemia: therapeutic targets, pathways and inhibitors. J Nucl Med Radiat Ther 6:1–7. https://doi.org/10.4172/2155-9619.1000257

    CAS  Article  Google Scholar 

  26. Kurczab R (2017) The evaluation of QM/MM-driven molecular docking combined with MM/GBSA calculations as a halogen-bond scoring strategy. Act Crystallograph B73:188–194. https://doi.org/10.1107/S205252061700138X

    Article  Google Scholar 

  27. Lavecchia A (2014) Machine-learning approaches in drug discovery: methods and applications. Drug Discov Today 20:318–331. https://doi.org/10.1016/j.drudis.2014.10.012

    Article  PubMed  Google Scholar 

  28. Lu X, Wang Y, Zhu W (2010) Nonbonding interactions of organic halogens in biological systems: implications for drug discovery and biomolecular design. Phys Chem Chem Phys 12:4543–04551. https://doi.org/10.1039/B926326H

    CAS  Article  PubMed  Google Scholar 

  29. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639–1662. https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14%3c1639:AID-JCC10%3e3.0.CO;2-B

    CAS  Article  Google Scholar 

  30. Neochoritis CG, Zhao T, Dömling A (2019) Tetrazoles via multicomponent reactions. Chem Rev 119:1970–2024. https://doi.org/10.1021/acs.chemrev.8b00564

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. O’Hare T, Shakespeare WC et al (2009) AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 16:401–412. https://doi.org/10.1016/j.ccr.2009.09.028

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Pemovska T, Johnson E, Kontro M, Repasky GA, Chen J, Wells P, Cronin CN, McTigue M, Kallioniemi O, Porkka K, Murray BW, Wennerberg K (2015) Axitinib effectively inhibits BCR-ABL1 (T315I) with a distinct binding conformation. Nature 5:102–105. https://doi.org/10.1038/NATURE14119

    Article  Google Scholar 

  33. Pires DEV, Blundell TL, Ascher DB (2015) pKCSM: predicting small-molecule pharmacokinetic properties using graph-based signatures. J Med Chem 58:4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Regier A, Khuu P, Oishi K, Shing Ho P (2009) Halogen bonds as orthogonal molecular interactions to hydrogen bonds. Nat Chem 1:74–79. https://doi.org/10.1038/nchem.112

    CAS  Article  Google Scholar 

  35. Rose PW, Prlic A, Bi C, Bluhm WF et al (2015) The RCSB protein Data Bank: views of structural biology for basic and applied research and education. Nucl Acids Res 43:345–356. https://doi.org/10.1093/nar/gku1214

    CAS  Article  Google Scholar 

  36. Sanner MF (1999) Python: a programming language for software integration and development. J Mol Graph Model 17:57–61. https://doi.org/10.1016/S1093-3263(99)99999-0

    CAS  Article  PubMed  Google Scholar 

  37. Sirimulla S, Bailey JB, Vegesna R, Narayan M (2013) Halogen interactions in protein-ligand complexes: implications of halogen bonding for rational drug design. J Chem Inf Model 53:2781–2791. https://doi.org/10.1021/ci400257k

    CAS  Article  PubMed  Google Scholar 

  38. Swain M (2012) Chemicalize.org. J Chem Inf Model 52:613–615. https://doi.org/10.1021/ci300046g

    CAS  Article  Google Scholar 

  39. Triballeau N, Acher F, Brabet I, Pin JP, Bertrand HO (2005) Virtual screening workflow development guided by the “receiver operating characteristic” curve approach. Application to high-throughput docking on metabotropic glutamate receptor subtype 4. J Med Chem 48:2534–2547. https://doi.org/10.1021/jm049092j

    CAS  Article  PubMed  Google Scholar 

  40. Vardhan S, Sahoo SK (2020) In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19. Comput Biol Med 124:103936. https://doi.org/10.1016/j.compbiomed.2020.103936

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. Von Bubnoff N, Duyster J (2010) Chronic myelogenous leukemia: treatment and monitoring. Dtsch Arztebl Int 107:114–121. https://doi.org/10.3238/arztebl.2010.0114

    Article  Google Scholar 

  42. Wu P, Nielsen TE, Clausen M (2016) Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discov Today 21:5–10. https://doi.org/10.1016/j.drudis.2015.07.008

    CAS  Article  PubMed  Google Scholar 

  43. Yang JM, Chen CCJ (2004) GEMDOCK: a generic evolutionary method for molecular docking. Proteins 55:288–304. https://doi.org/10.1002/prot.20035

    CAS  Article  PubMed  Google Scholar 

  44. Zhang J, Wang S, Ba Y, Xu Z (2019) Tetrazole hybrids with potential anticancer activity. Eur J Med Chem 178:341–351. https://doi.org/10.1016/j.ejmech.2019.05.071

    CAS  Article  PubMed  Google Scholar 

  45. Zhou T, Parillon L, Li F, Wang Y, Keats J, Lamore S, Xu Q, Shakespeare W, Dalgarno D, Zhu X (2007) Crystal structure of the T315I mutant of Abl kinase. Chem Biol Drug Des 70:171–181. https://doi.org/10.1111/j.1747-0285.2007.00556.x

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank to CONACyT for the fellowship 305150.

Funding

Carlos, C.-G. is grateful for financial support from CIC-UMSNH (14646).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Carlos J. Cortés-García or Abel Suárez-Castro.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Díaz-Cervantes, E., Cortés-García, C.J., Chacón-García, L. et al. Molecular docking and pharmacophoric modelling of 1,5-disubstituted tetrazoles as inhibitors of two proteins present in cancer, the ABL and the mutated T315I kinase. In Silico Pharmacol. 8, 6 (2020). https://doi.org/10.1007/s40203-020-00059-6

Download citation

Keywords

  • Docking
  • Pharmacophore-model
  • 1,5-DS-T
  • ABL kinase
  • Mutant T315I
  • Anticancer