Development of kNN QSAR Models for 3-Arylisoquinoline Antitumor Agents

다국어 초록 (Multilingual Abstract)

Variable selection k nearest neighbor QSAR modeling approach was applied to a data set of 80 3-arylisoquinolines exhibiting cytotoxicity against human lung tumor cell line (A-549). All compounds were characterized with molecular topology descriptors calculated with the MolconnZ program. Seven compounds were randomly selected from the original dataset and used as an external validation set. The remaining subset of 73 compounds was divided into multiple training (56 to 61 compounds) and test (17 to 12 compounds) sets using a chemical diversity sampling method developed in this group. Highly predictive models characterized by the leave-one out cross-validated R^2 (q^2) values greater than 0.8 for the training sets and R^2 values greater than 0.7 for the test sets have been obtained. The robustness of models was confirmed by the Y-randomization test: all models built using training sets with randomly shuffled activities were characterized by low q^2 ≤ 0.26and R^2 ≤ 0.22 for training and test sets, respectively. Twelve best models (with the highest values of both q^2and R^2) predicted the activities of the external validation set of seven compounds with R^2 ranging from 0.71 to 0.93.

참고문헌 (Reference)

1 Cook, S. J, 5 : 341-, 2005

2 Fan, Q. L, 55 : 189-, 2005

3 Inagawa, H, 18 : 3957-, 1998

4 Le, T. N, 45 : 2763-, 2004

5 Nakanishi, T, 10 : 2321-, 2000

6 Vogt, A, 280 : 19078-, 2005

7 Cho, W. J, 8 : 41-, 1998

8 Cho, W. J, 47 : 900-, 1999

9 Cho, W. J, 13 : 4451-, 2003

10 Lee, S. H, 19 : 2444-, 2009

11 Van, H. T. M, 17 : 5763-, 2007

12 Cho, W. J, 17 : 3531-, 2007

13 Ioanoviciu, A, 48 : 4803-, 2005

14 Staker, B. L, 48 : 2336-, 2005

15 Xiao, X, 48 : 3231-, 2005

16 Cho, W. J, 10 : 2953-, 2002

17 Kim, K. E, 217 : 101-, 2001

18 Kim, K. E, 28 : 889-, 2002

19 Cramer III, R. D, 110 : 5959-, 1988

20 Marshall, G. R, 9 : 285-, 1988

21 Cho, S. J, 38 : 1060-, 1995

22 Kubinyi, H, 41 : 2553-, 1998

23 Pérez, C, 41 : 836-, 1988

24 Golbraikh, A, 41 : 147-, 2001

25 Allen, F. H, B 35 : 2331-, 1979

26 Ewing, T. J, 15 : 411-, 2001

27 Morris, G. M, 4 : 293-, 1996

28 Osterberg, F, 46 : 34-, 2002

29 Jones, G, 245 : 43-, 1995

30 Verdonk, M. L, 52 : 609-, 2003

31 Holloway, M. K, 38 : 305-, 1995

32 Kramer, B, 37 : 228-, 1999

33 Claussen, H, 27 : 377-, 2001

34 Cho, S. J, 39 : 5064-, 1996

35 Pilger, C, 19 : 288-, 2001

36 Shen, M, 47 : 2356-, 2004

37 Oloff, S, 48 : 7322-, 2005

38 Shen, M, 45 : 2811-, 2002

39 Hoffman, B, 42 : 3217-, 1999

40 Zheng, W, 40 : 185-, 2000

41 Cho, S. J, 38 : 259-, 1998

42 Cho, S. J, 305-, 1998

43 Zheng, W, 38 : 251-, 1998

44 Rubinstein, L. V, 82 : 1113-, 1990

45 Randic, M, 97 : 6609-, 1975

46 Kier, L. B, 4 : 109-, 1985

47 Kier, L. B, 6 : 8-, 1987

48 Hall, L. H, 9 : 115-, 1990

49 Hall, L. H, 31 : 76-, 1991

50 Hall, L. H, 10 : 43-, 1991

51 Kellogg, G. E, 10 : 513-, 1996

52 Kier, L. B, 10 : 134-, 1991

53 Petitjean, M, 32 : 331-, 1992

54 Wiener, H. J, 69 : 17-, 1947

55 Platt, J. R, 15 : 419-, 1947

56 Bonchev, D, 2 : 127-, 1981

57 Basak, S. C, 12 : 481-, 2001

58 Benigni, R, 100 : 3697-, 2000

59 Cronin, M. T, 13 : 167-, 2002

60 Fan, Y, 44 : 3254-, 2001

61 Girones, X, 40 : 1400-, 2000

62 Moss, G. P, 16 : 299-, 2002

63 Randic, M, 40 : 899-, 2000

64 Suzuki, T, 41 : 718-, 2001

65 Trohalaki, S, 24 : 421-, 2000

66 Wang, X, 46 : 1045-, 2002

67 Golbraikh, A, 20 : 269-, 2002

68 Golbraikh, A, 17 : 241-, 2003

69 Golbraikh, A, 16 : 357-, 2002

70 Pintore, M, 22 : 210-, 2003

71 Zhang, S, 49 : 2713-, 2006

72 Golbraikh, A, 42 : 769-, 2002

73 Tropsha, A, 13 : 3494-, 2007

74 Wold, S. a. E. L, "Statistical Validation of QSAR Results, In Chemometrics Methods in Molecular Design" VCH 1995

75 Kier, L. B, "Molecular Structure Description: The Electrotopological State" Academic Press 1999

76 Kier, L. B, "Molecular Connectivity in Chemistry and Drug Research" Academic Press 1986

77 Kier, L. B. H, "Molecular Connectivity in Chemistry and Drug Research" Academic Press 1976

78 Shannon, C, "In Mathematical Theory of Communication" University of Illinois 1949

79 Judson, R, "Genetic Algorithms and Their Use in Chemistry, In Reviews in Computational Chemistry" VCH 1997

80 Klebe, G, "Comparative Molecular Similarity Indices Analysis- CoMSIA. In 3D QSAR in Drug Design" Kluwer/ESCOM 1988