Journal of Molecular Modeling

, Volume 11, Issue 6, pp 525–531

Topochemical models for prediction of cyclin-dependent kinase 2 inhibitory activity of indole-2-ones

Original Paper

Abstract

The relationship between the topochemical indices and cyclin-dependent kinase 2 (CDK2) inhibitory activity of indole-2-ones has been investigated. The relationship of topochemical versions of well known topological indices of Wiener’s index—a distance-based topological descriptor, molecular connectivity index, an adjacency-based topological descriptor and eccentric connectivity index—an adjacency-cum-distance based topological descriptor with CDK2 inhibitory activity of indole-2-ones has been investigated. A data set comprising 67 analogues of substituted indole-2-ones was selected for the present investigation. The values of the Wiener’s topochemical index, molecular connectivity topochemical index and eccentric connectivity topochemical index for each of 67 analogues comprising the data set were computed. The resulting data was analyzed and suitable models developed after identification of the active ranges. Subsequently, a biological activity was assigned to each analogue in the data set using these models, which was then compared with the reported CDK2 inhibitory activity. Accuracy of prediction was found to vary from a minimum of 88% for a model based upon molecular connectivity topochemical index to a maximum of ~90% for model based upon eccentric connectivity topochemical index.

Keywords

Topochemical indices Wiener’s topochemical index Molecular connectivity topochemical index Atomic molecular connectivity index Eccentric connectivity topochemical index CDK2 inhibitory activity Indole-2-ones 

References

  1. 1.
    Basak SC (1987) Med Sci Res 15:605–609Google Scholar
  2. 2.
    Basak SC, Niemi GJ, Veith GD (1990) J Math Chem 4:185–205CrossRefGoogle Scholar
  3. 3.
    Randic M (1975) J Am Chem Soc 97:6609–6615CrossRefGoogle Scholar
  4. 4.
    Magnuson VR, Harriss DK, Basak SC (1983) In: King RB (ed) Chemical applications of topology and graph theory. Elsevier, Amsterdam, p 178Google Scholar
  5. 5.
    Basak SC, Harriss DK, Magnuson VR (1984) J Pharm Sci 73:429–437PubMedCrossRefGoogle Scholar
  6. 6.
    Randic M (1984) Int J Quantum Chem Quant Biol Symp 11:137–153CrossRefGoogle Scholar
  7. 7.
    Kier LB, Hall LH (1986) Molecular connectivity in structure-activity analysis. Research studies press, Letchworth, England, pp 1–262Google Scholar
  8. 8.
    Basak SC (1988) Med Sci Res 16:281–282Google Scholar
  9. 9.
    Trinajstic N (1983) Chemical graph theory, vols 1 and 2. CRC Press, Boca Raton, FLGoogle Scholar
  10. 10.
    Harary F (1969) Graph theory. Addison-Wesley publishing company, Reading, MAGoogle Scholar
  11. 11.
    Basak SC, Balaban AT, Grunwald GD, Gute BD (2000) J Chem Inf Comput Sci 40:891–898PubMedCrossRefGoogle Scholar
  12. 12.
    Hosoya H (1971) Bull Chem Soc Jpn 44:2332–2337CrossRefGoogle Scholar
  13. 13.
    Hosoya H (1972) J Chem Doc 12:181–183CrossRefGoogle Scholar
  14. 14.
    Gupta S, Singh M, Madan AK (2001) J Mol Struct (THEOCHEM) 571:147–152CrossRefGoogle Scholar
  15. 15.
    Rose K, Hall LH, Kier LB (2002) J Chem Inf Comput Sci 42:651–656PubMedCrossRefGoogle Scholar
  16. 16.
    Hall LM, Hall LH, Kier LB (2003) J Chem Inf Comput Sci 43:2120–2128PubMedCrossRefGoogle Scholar
  17. 17.
    Balaban AT, Chiriac A, Motoc I, Simon Z (1980) Lect Notes Chem 15:22–27Google Scholar
  18. 18.
    Balaban AT (1982) Chem Phys Lett 89:399–404CrossRefGoogle Scholar
  19. 19.
    Balaban AT (1985) J Chem Inf Comput Sci 25:334–343CrossRefGoogle Scholar
  20. 20.
    Balaban AT, Filip P (1984) J Math Chem 16:163–190Google Scholar
  21. 21.
    Wiener H (1947) J Chem Phys 15:766–766CrossRefGoogle Scholar
  22. 22.
    Wiener H (1947) J Am Chem Soc 69:2636–2638CrossRefGoogle Scholar
  23. 23.
    Randic M, Guo X, Oxely T, Krishnapriyan H (1993) J Chem Inf Comput Sci 33:709–716CrossRefGoogle Scholar
  24. 24.
    Gutman I, Randic M (1977) Chem Phys Lett 47:15–19CrossRefGoogle Scholar
  25. 25.
    Gutman I, Ruscic B, Trinajstic N, Wilcox CF (1975) J Chem Phys 62:3399–3405CrossRefGoogle Scholar
  26. 26.
    Sharma V, Goswami R, Madan AK (1997) J Chem Inf Comput Sci 37:273–282CrossRefGoogle Scholar
  27. 27.
    Sardana S, Madan AK (2001) MATCH Commun Math Comput Chem 43:85–98Google Scholar
  28. 28.
    Sardana S, Madan AK (2002) J Comput Aid Mol Des 16:1–6CrossRefGoogle Scholar
  29. 29.
    Sardana S, Madan AK (2002) J Mol Model 8:258–265CrossRefGoogle Scholar
  30. 30.
    Gupta S, Singh M, Madan AK (2002) J Math Anal Applic 266:259–268CrossRefGoogle Scholar
  31. 31.
    Sardana S, Madan AK (2002) MATCH Commun Math Comput Chem 45:36–53Google Scholar
  32. 32.
    Kumar V, Madan AK (2004) MATCH Commun Math Comput Chem 51:59–78MathSciNetGoogle Scholar
  33. 33.
    Webster KR (1998) Expert Opin Invest Drugs 7:865–887CrossRefGoogle Scholar
  34. 34.
    Meijer L, Leclerc S, Leost M (1999) Pharmacol Ther 82:279–284CrossRefPubMedGoogle Scholar
  35. 35.
    Garrett MD, Fattaey A (1999) Curr Opin Genet Dev 9:104–111PubMedCrossRefGoogle Scholar
  36. 36.
    Davis ST, Benson BG, Bramson HN, Chapman DE, Dickerson SH (2001) Science 291:134–137CrossRefPubMedGoogle Scholar
  37. 37.
    Morgan DO (1997) Annu Rev Cell Div Bio 13:261–291CrossRefGoogle Scholar
  38. 38.
    Lenobel R, Havli L, Kryscaron PV, Otyepka M, Strnad M (2001) Scientific World J 1(suppl 3):128Google Scholar
  39. 39.
    Pavletich NP (1999) J Mol Biol 287:821–828CrossRefPubMedGoogle Scholar
  40. 40.
    Malumbers M, Ortega S, Barbacid M (2000) Biol Chem 381:827–838CrossRefPubMedGoogle Scholar
  41. 41.
    Nikolic M, Tsai LH (2000) Methods Enzymol 325:200–213PubMedCrossRefGoogle Scholar
  42. 42.
    Maccioni RB, Otth C, Concha II, Munoz JP (2001) Eur J Biochem 268:1518–1527CrossRefPubMedGoogle Scholar
  43. 43.
    Dhavan R, Tsai LH (2001) Nat Rev Mol Cell Biol 2:749–759CrossRefPubMedGoogle Scholar
  44. 44.
    Gladden AB, Diehl JA (2003) Cancer Cell 4:160–162CrossRefPubMedGoogle Scholar
  45. 45.
    Pardee AB (1974) Proc Natl Acad Sci USA 71:1286–1290PubMedCrossRefGoogle Scholar
  46. 46.
    Paulovich AG, Toczyski DP, Hartwell LH (1997) Cell 88:315–321CrossRefPubMedGoogle Scholar
  47. 47.
    Grant S, Roberts JD (2003) Drug Resist Updat 6:15–26CrossRefPubMedGoogle Scholar
  48. 48.
    Fischer PM, Lane DP (2000) Curr Med Chem 7:1213–1245PubMedGoogle Scholar
  49. 49.
    Sielecki TM, Boylan JF, Benfield PA, Trainor GL (2000) J Med Chem 43:1–18CrossRefGoogle Scholar
  50. 50.
    Kelland LR (2000) Expert Opin Invest Drugs 9:2903–2911CrossRefGoogle Scholar
  51. 51.
    Senderowicz AM, Headlee D, Stinson SF, Lush RM, Kalil N (1998) J Clin Oncol 16:2986–2999PubMedGoogle Scholar
  52. 52.
    Webster KR (2000) Chem Res Toxicol 13:940–943CrossRefPubMedGoogle Scholar
  53. 53.
    Knockaert M, Greengard P, Meijer L (2002) Trends Pharmacol Sci 23:417–425CrossRefPubMedGoogle Scholar
  54. 54.
    Randic M (1993) Chem Phys Lett 211:478–483CrossRefGoogle Scholar
  55. 55.
    Gutman I (2004) Croat Chem Acta 77:61–64Google Scholar
  56. 56.
    Bajaj S, Sambi SS, Madan AK (2004) J Mol Struct (THEOCHEM) 684:197–203CrossRefGoogle Scholar
  57. 57.
    Goel A, Madan AK (1995) J Chem Inf Comput Sci 35:510–514CrossRefPubMedGoogle Scholar
  58. 58.
    Bajaj S, Sambi SS, Madan AK (2005) Croat Chem Acta (in press)Google Scholar
  59. 59.
    Kumar V, Sardana S, Madan AK (2004) J Mol Mod 10:399–407CrossRefGoogle Scholar
  60. 60.
    Bramson HN, Corona J, Davis ST, Dickerson SH, Edelstein M, Frye SV, Gampe RT, Harris PA Jr, Hassell A, Holmes WD, Hunter RN, Lackey KE, Lovejoy B, Luzzio MJ, Montana V, Rocque WJ, Rusnak D, Shewchuk L, Veal JM, Walker DH, Kuyper LF (2001) J Med Chem 44:4339–4358CrossRefPubMedGoogle Scholar
  61. 61.
    Gupta S, Singh M, Madan AK (2001) J Comput Aid Mol Des 15:671–678CrossRefGoogle Scholar
  62. 62.
    Balaban AT, Motoc I, Bonchev D, Mekennyan O (1983) Top Curr Chem 114:21–55Google Scholar
  63. 63.
    Basak SC, Bertlsen S, Grunwold GD (1994) J Chem Inf Comput Sci 34:270–276CrossRefGoogle Scholar
  64. 64.
    Ruetz S, Fabbro D, Zimmermann J, Meyer T, Gray N (2003) Curr Med Chem Anti-Canc Agents 3:1–14CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Faculty of Pharmaceutical SciencesM. D. UniversityRohtakIndia

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