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Bond-based 2D TOMOCOMD-CARDD approach for drug discovery: aiding decision-making in ‘in silico’ selection of new lead tyrosinase inhibitors

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Abstract

In this paper, we present a new set of bond-level TOMOCOMD-CARDD molecular descriptors (MDs), the bond-based bilinear indices, based on a bilinear map similar to those defined in linear algebra. These novel MDs are used here in Quantitative Structure–Activity Relationship (QSAR) studies of tyrosinase inhibitors, for finding functions that discriminate between the tyrosinase inhibitor compounds and inactive ones. In total 14 models were obtained and the best two discriminant functions (Eqs. 32 and 33) shown globally good classification of 91.00% and 90.17%, respectively, in the training set. The test set had accuracies of 93.33% and 88.89% for the models 32 and 33, correspondingly. A simulated virtual screening was also carried out to prove the quality of the determined models. In a final step, the fitted models were used in the biosilico identification of new synthesized tetraketones, where a good agreement could be observed between the theoretical and experimental results. Four compounds of the novel bioactive chemicals discovered as tyrosinase inhibitors: TK10 (IC50 = 2.09 μM), TK11 (IC50 = 2.61 μM), TK21 (IC50 = 2.06 μM), TK23 (IC50 = 3.19 μM), showed more potent activity than l-mimose (IC50 = 3.68 μM). Besides, for this study a heterogeneous database of tyrosinase inhibitors was collected, and could be a useful tool for the scientist in the domain of tyrosinase enzyme researches. The current report could help to shed some clues in the identification of new chemicals that inhibits enzyme tyrosinase, for entering in the pipeline of drug discovery development.

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References

  1. Robb DA (1984) Copper proteins and copper enzymes. CRC Press, Boca Raton, FL

    Google Scholar 

  2. Baurin N, Arnoult E, Scior T, Do QT, Bernard P (2002) J Ethnopharmacol 82:155

    Article  CAS  Google Scholar 

  3. Prota G (1988) Med Res Rev 8:525

    Article  CAS  Google Scholar 

  4. Prota G (1992) Melanins and melanogenesis. Academic Press, San Diego, CA

    Google Scholar 

  5. Riley PA (1996) In: Hori Y, Hearing VJ, Nakayama J (eds) Melanogenesis and malignant melanoma: biochemistry, cell biology, molecular biology, pathophysiology, diagnosis and treatment. Elsevier, Amsterdam

    Google Scholar 

  6. Riley PA (2003) Pigment Cell Res 16:548

    Article  CAS  Google Scholar 

  7. Fitzpatrick TB, Seji M, McGugan AD (1961) New Engl J Med 265:374

    Article  CAS  Google Scholar 

  8. Maeda K, Fukuda M (1996) J Pharmacol Exp Ther 276:765

    CAS  Google Scholar 

  9. Li W, Kubo I (2004) Bioorg Med Chem 12:701

    Article  CAS  Google Scholar 

  10. Casañola-Martin GM, Khan MT, Marrero-Ponce Y, Ather A, Sultankhodzhaev MN, Torrens F (2006) Bioorg Med Chem Lett 16:324

    Article  CAS  Google Scholar 

  11. Marrero-Ponce Y, Khan MTH, Casañola-Martín GM, Ather A, Sultankhodzhaev MN, Torrens F (2006) QSAR Comb Sci DOI: 10.1002/qsar.200610156

  12. Marrero-Ponce Y (2003) Molecules 8:687

    Google Scholar 

  13. Marrero-Ponce Y, Huesca-Guillen A, Ibarra-Velarde F (2005) J Mol Struct (Theochem) 717:67

    Article  CAS  Google Scholar 

  14. Meneses-Marcel A, Marrero-Ponce Y, Machado-Tugores Y, Montero-Torres A, Pereira DM, Escario JA, Nogal-Ruiz JJ, Ochoa C, Aran VJ, Martinez-Fernandez AR, Garcia Sanchez RN (2005) Bioorg Med Chem Lett 15:3838

    Article  CAS  Google Scholar 

  15. Vega MC, Montero-Torres A, Marrero-Ponce Y, Rolon M, Gomez-Barrio A, Escario JA, Aran VJ, Nogal JJ, Meneses-Marcel A, Torrens F (2006) Bioorg Med Chem Lett 16:1898

    Article  CAS  Google Scholar 

  16. Marrero-Ponce Y, Medina-Marrero R, Martinez Y, Torrens F, Romero-Zaldivar V, Castro EA (2006) J Mol Mod 12:255

    Article  CAS  Google Scholar 

  17. Marrero-Ponce Y, Nodarse D, González HD, Ramos de Armas R, Romero-Zaldivar V, Torrens F, Castro E (2004) Int J Mol Sci 5:276

    Google Scholar 

  18. Marrero Ponce Y, Castillo Garit JA, Nodarse D (2005) Bioorg Med Chem 13:3397

    Article  CAS  Google Scholar 

  19. Marrero-Ponce Y, Iyarreta-Veitia M, Montero-Torres A, Romero-Zaldivar C, Brandt CA, Avila PE, Kirchgatter K, Machado Y (2005) J Chem Inf Model 45:1082

    Article  CAS  Google Scholar 

  20. Marrero-Ponce Y, Romero V, TOMOCOMD software, Central University of Las Villas (2002) TOMOCOMD (TOpological MOlecular COMputer Design) for Windows, version 1.0 is a preliminary experimental version; in future a professional version can be obtained upon request to Y. Marrero: yovanimp@qf.uclv.edu.cu or ymarrero77@yahoo.es

  21. Rouvray DH (1976) In: Balaban AT (ed) Chemical applications of graph theory. Academic Press, London, pp 180–181

    Google Scholar 

  22. Trinajstić N (1983) Chemical graph theory. CRC Press, Boca Raton FL

    Google Scholar 

  23. Estrada E (1995) J Chem Inf Comput Sci 35:31

    Article  CAS  Google Scholar 

  24. Estrada E, Ramirez A (1996) J Chem Inf Comput Sci 36:837

    Article  CAS  Google Scholar 

  25. Estrada E (1996) J Chem Inf Comput Sci 36:844

    Article  CAS  Google Scholar 

  26. Estrada E, Guevara N, Gutman I (1998) J Chem Inf Comput Sci 38:428

    Article  CAS  Google Scholar 

  27. Estrada E (1999) J Chem Inf Comput Sci 39:1042

    Article  CAS  Google Scholar 

  28. Estrada E, Molina E (2001) J Mol Graph Model 20:54

    Article  CAS  Google Scholar 

  29. Todeschini R, Consonni V (2000) Handbook of molecular descriptors. Wiley-VCH, Germany

    Google Scholar 

  30. Ivanciuc O, Balaban AT (1999) In: Devillers J, Balaban AT (eds) Topological indices and related descriptors in QSAR and QSPR. Gordon and Breach, The Netherlands, 73 p

    Google Scholar 

  31. Edwards CH, Penney DE (1988) Elementary linear algebra. Prentice-Hall, Englewood Cliffs, New Jersey, USA

    Google Scholar 

  32. Marrero-Ponce Y (2004) Bioorg Med Chem 12:6351

    Article  CAS  Google Scholar 

  33. Marrero-Ponce Y, Castillo-Garit JA, Olazabal E, Serrano HS, Morales A, Castañedo N, Ibarra-Velarde F, Huesca-Guillen A, Jorge E, del Valle A, Torrens F, Castro EA (2004) J Comput Aided Mol Des 18:615

    Article  CAS  Google Scholar 

  34. Marrero-Ponce Y, Medina-Marrero R, Torrens F, Martinez Y, Romero-Zaldivar V, Castro EA (2005) Bioorg Med Chem 13:2881

    Article  CAS  Google Scholar 

  35. Marrero-Ponce Y, Díaz HG, Romero V, Torrens F, Castro EA (2004) Bioorg Med Chem 12:5331

    Article  CAS  Google Scholar 

  36. Marrero-Ponce Y, Cabrera MA, Romero V, Ofori E, Montero LA (2003) Int J Mol Sci 4:512

    Google Scholar 

  37. Marrero-Ponce Y, Cabrera MA, Romero V, González DH, Torrens F (2004) J Pharm Pharmaceut Sci 7:186

    Google Scholar 

  38. Marrero-Ponce Y, Cabrera MA, Romero-Zaldivar V, Bermejo M, Siverio D, Torrens F (2005) Internet Electron J Mol Des 4:124

    Google Scholar 

  39. Marrero-Ponce Y, Medina R, Castro EA, de Armas R, González H, Romero V, Torrens F (2004) Molecules 9:1124

    Google Scholar 

  40. Marrero Ponce Y (2004) J Chem Inf Comput Sci 44:2010

    Article  CAS  Google Scholar 

  41. Marrero-Ponce Y, Castillo-Garit JA, Torrens F, Romero-Zaldivar V, Castro E (2004) Molecules 9:1100

    Google Scholar 

  42. Marrero-Ponce Y, Montero-Torres A, Zaldivar CR, Veitia MI, Perez MM, Sanchez RN (2005) Bioorg Med Chem 13:1293

    Article  CAS  Google Scholar 

  43. Marrero-Ponce Y, Castillo-Garit JA, Olazabal E, Serrano HS, Morales A, Castanedo N, Ibarra-Velarde F, Huesca-Guillen A, Sanchez AM, Torrens F, Castro EA (2005) Bioorg Med Chem 13:1005

    Article  CAS  Google Scholar 

  44. Marrero-Ponce Y, Castillo-Garit JA (2005) J Comput Aided Mol Des 19:369

    Article  CAS  Google Scholar 

  45. Estrada E, Vilar S, Uriarte E, Gutierrez Y (2002) J Chem Inf Comput Sci 42:1194

    Article  CAS  Google Scholar 

  46. Estrada E, Uriarte E, Montero A, Teijeira M, Santana L, De Clercq E (2000) J Med Chem 43:1975

    Article  CAS  Google Scholar 

  47. Estrada E, Peña A, Garcia-Domenech R (1998) J Comput Aided Mol Des 12:583

    Article  CAS  Google Scholar 

  48. Potapov VM (1978) Stereochemistry. Mir Moscow

  49. Wang R, Gao Y, Lai L (2000) Perspect Drug Dis Des 19:47

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  51. Ghose AK, Crippen GM (1987) J Chem Inf Comput Sci 27:21

    Article  CAS  Google Scholar 

  52. Miller KJ (1990) J Am Chem Soc 112:8533

    Article  CAS  Google Scholar 

  53. Gasteiger J, Marsili M (1978) Tetrahedron Lett 19:3181

    Article  Google Scholar 

  54. Pauling L (1939) The nature of chemical bond. Cornell University Press, Ithaca, New York

    Google Scholar 

  55. Kier LB, Hall LH (1986) Molecular connectivity in structure–activity analysis. Research Studies Press, Letchworth, UK

    Google Scholar 

  56. Consonni V, Todeschini R, Pavan M (2002) J Chem Inf Comput Sci 42:682

    Article  CAS  Google Scholar 

  57. Todeschini R, Gramatica P (1998) Perspect Drug Dis Des 9–11:355

    Article  Google Scholar 

  58. Jacobson N (1985) In: Freeman WHC (ed) Basic algebra I. New York, pp 343–361

  59. Riley KF, Hobson MP, Vence SJ (1998) Mathematical methods for physics and engineering. Cambridge University Press

  60. Werner G (1981) Linear algebra, 4th edn Springer-Verlag, New York

    Google Scholar 

  61. Walker PD, Mezey PG (1993) J Am Chem Soc 115:12423

    Article  CAS  Google Scholar 

  62. Klein DJ (2003) Internet Electron J Mol Des 2:814

    CAS  Google Scholar 

  63. Negwer M (1987) Organic-chemical drugs and their synonyms. Akademie-Verlag, Berlin

    Google Scholar 

  64. STATISTICA (data analysis software system), v S I (2001) www.statsoft.com

  65. Xu J, Hagler A (2002) Molecules 7:566

    Article  CAS  Google Scholar 

  66. Mc Farland JW, Gans DJ (1995) In: Waterbeemd H (ed), Chemometric Methods in Molecular Design. VCH Publishers, New York, pp 295–307

    Google Scholar 

  67. Johnson RA, Wichern DW (1988) Applied multivariate statistical analysis. Prentice-Hall, New Jersey

    Google Scholar 

  68. Duart MJ, Garcia-Domenech R, Anton-Fos GM, Galvez J (2001) J Comput Aided Mol Des 15:561

    Article  CAS  Google Scholar 

  69. van de Waterbeemd H (1995) In: van de Waterbeemd H (ed) Chemometric methods in molecular design. VCH Publishers, Weinheim, pp 265–288

    Google Scholar 

  70. de Julian-Ortiz JV, de Alapont CG, Ríos-Santamarina I, Garcia-Domenech R, Galvez E (1998) J Mol Graphics Mod 16:14

    Article  Google Scholar 

  71. Gálvez J, García R, Salabert MT, Soler R (1994) J Chem Inf Comput Sci 34:520

    Article  Google Scholar 

  72. Gonzales-Diaz H, Marrero Ponce Y, Hernadez I, Bastida I, Tenorio E, Nasco O, Uriarte E, Castanedo N, Cabrera MA, Aguila E, Marrero O, Morales A, Perez M (2003) Chem Res Toxicol 16:1318

    Article  CAS  Google Scholar 

  73. Estrada E, Peña A (2000) Bioorg Med Chem 8:2755

    Article  CAS  Google Scholar 

  74. Randić M (1991) J Mol Struct (Theochem) 233:45

    Article  Google Scholar 

  75. Randić M (1991) J Chem Inf Comput Sci 31:311

    Article  Google Scholar 

  76. Randić M (1991) New J Chem 15:517

    Google Scholar 

  77. Lučić B, Nikolić S, Trinajstić N, Jurić D (1995) J Chem Inf Comput Sci 35:532

    Google Scholar 

  78. Klein DJ, Randić M, Babić D, Lučić B, Nikolić S, Trinajstić N (1997) Int J Quantum Chem 63:215

    Article  CAS  Google Scholar 

  79. Estrada E, Uriarte E (2001) Curr Med Chem 8:1573

    CAS  Google Scholar 

  80. Khan KM, Maharvi GM, Khan MT, Jabbar Shaikh A, Perveen S, Begum S, Choudhary MI (2006) Bioorg Med Chem 14:344

    Article  CAS  Google Scholar 

  81. Hearing VJ (1987) Methods in enzymology. Academic Press, New York

    Google Scholar 

  82. Wold S, Erikson L (1995) In: van de Waterbeemd H (ed) Chemometric methods in molecular design. VCH Publishers, New York, pp 309–318

    Google Scholar 

  83. Golbraikh A, Tropsha A (2002) J Mol Graph Model 20:269

    Article  CAS  Google Scholar 

  84. Okombi S, Rival D, Bonnet S, Mariotte AM, Perrier E, Boumendjel A (2006) J Med Chem 49:329

    Article  CAS  Google Scholar 

  85. Zhang J-P, Chen Q-X, Song K-K, Xie J-J (2006) Food Chem 92:579

    Article  CAS  Google Scholar 

  86. Apweiler R (2003) Biosilico 1:5

    Article  Google Scholar 

Download references

Acknowledgments

One of the authors (M-P. Y) thanks the program ‘Estades Temporals per a Investigadors Convidats’ for a fellowship to work at Valencia University (2006–2007). M-P. Y thanks are also given to the Generalitat Valenciana, (Spain) for partial financial support as well as support from Spanish MEC (Project Reference: SAF2006-04698). MTHK is the recipient of a grant from MCBN-UNESCO (grant no. 1056), and fellowships from CIB (Italy) and Associasione Veneta per la Lotta alla Talassemia (AVTL, Italy). F. T. acknowledges financial support from the Spanish MEC DGI (Project No.CTQ2004-07768-C02-01/BQU) and Generalitat Valenciana (DGEUI INF01-051 and INFRA03-047, and OCYT GRUPOS03-173.

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Authors and Affiliations

  1. Institut Universitari de Ciència Molecular, Universitat de València, Edifici d’Instituts de Paterna, Poligon la Coma s/n (detras de Canal Nou), P.O. Box 22085, 46071, Valencia, Spain

    Yovani Marrero-Ponce & Francisco Torrens

  2. Unit of Computer-Aided Molecular “Biosilico” Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Department of Drug Design, Chemical Bioactive Center, Central University of Las Villas, Santa Clara, Villa Clara, 54830, Cuba

    Yovani Marrero-Ponce & Gerardo M. Casañola-Martín

  3. Unidad de Investigación de Diseño de Fármacos y Conectividad Molecular, Departamento de Química Física, Facultad de Farmacia, Universitat de València, Valencia, Spain

    Yovani Marrero-Ponce & Ramón García-Domenech

  4. Pharmacology Research Lab., Faculty of Pharmaceutical Sciences, University of Science and Technology, Chittagong, Bangladesh

    Mahmud Tareq Hassan Khan

  5. Department of Pharmacology, Institute of Medical Biology, University of Tromso, Tromso, 9037, Norway

    Mahmud Tareq Hassan Khan

  6. Department of Biological Sciences, Faculty of Agricultural Sciences, University of Ciego de Avila, 69450, Ciego de Avila, Cuba

    Gerardo M. Casañola-Martín

  7. The Norwegian Structural Biology Centre (NorStruct), University of Tromso, Tromso, 9037, Norway

    Arjumand Ather

  8. S. Yunusov Institute of Chemistry of Plant Substances, Academy of Sciences, Uzbekistan, Tashkent

    Mukhlis N. Sultankhodzhaev

  9. Advanced Medisyns, Inc., 601 Carlson Parkway, Suite 1050, Minnetonka, MN, 55305, USA

    Richard Rotondo

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  1. Yovani Marrero-Ponce
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  2. Mahmud Tareq Hassan Khan
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  3. Gerardo M. Casañola-Martín
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  6. Ramón García-Domenech
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  7. Francisco Torrens
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Correspondence to Yovani Marrero-Ponce.

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Y. Marrero-Ponce address web: URL: www.uv.es/yoma

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Marrero-Ponce, Y., Khan, M.T.H., Casañola-Martín, G.M. et al. Bond-based 2D TOMOCOMD-CARDD approach for drug discovery: aiding decision-making in ‘in silico’ selection of new lead tyrosinase inhibitors. J Comput Aided Mol Des 21, 167–188 (2007). https://doi.org/10.1007/s10822-006-9094-7

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