Journal of Chemical Crystallography

, Volume 41, Issue 3, pp 255–275 | Cite as

Biological-Activity Predictions, Crystallographic Comparison and Role of Packing Interactions in Androstane Derivatives of Steroids

Review Paper
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Abstract

A total of 60 molecules of androstane derivatives of steroids (1–60) have been undertaken to predict their pharmacological effects, specific mechanisms of action, known toxicities, drug likeness, etc., by using the statistics of multilevel neighbourhoods of atoms (MNA) descriptors for active and inactive fragments. The biological activity spectra for substances have been correlated on SAR base (Structure–activity relationships data and knowledge base) which provides the different Pa (probability of activity) and Pi (probability of inactivity). The Lipinski’s rule predicts that all the androstane derivatives have stronger preponderance for “cancer-like-drug” molecules and some of their related analogous have been entered in the ANCI (American National Cancer Institute) database. Some selected bond distances and bond angles of interest have been taken into account and deviation of bond distances/bond angles, vis-a-vis the substitutional group and X–H···A intra/intermolecular hydrogen bonds have been discussed in detail. X–H···A intra/intermolecular hydrogen bonds in the identified molecules have been described with the standard distance and angle cut-off criteria. Dθ and dθ scatter plots for X–H···A intra-and intermolecular interactions are presented for better understanding of packing interactions existing among these derivatives. Comparison of contacts from H(C) to O and H(O) to O, vis-a-vis their crystal structure reveals that contacts from H(O) to O predominate over H(C) to O. Solvent–solute/solute–solvent interactions have also been investigated to understand more complicated processes that occur for biomolecules in aqueous solutions. Most of the molecules show high value of drug-likeness whereas molecule-3 (82.5%), 36 (87.2%), 41 (83.7%), 43 (86.5%) and 50 (85.9%) exhibit low value of drug-likeness, instead of observed range of 90.3–99.2%.

Graphical Abstract

Steroidal molecules are held in their defined 3-D structures by hydrogen bonds. The hydrogen bonding/solvent–solvent interactions for a steroidal molecule (androstane derivative) are plotted in Figure. The asymmetric unit cell in androstane derivative contains two crystallographically independent molecules and two acetic acid molecules. The two acetic acid molecules are connected to one another through solvent–solvent [O6(Acetic acid)–H6C(O6)···5′(Acetic acid); O6′(Acetic acid)–H6′C(O6′)···O5(Acetic acid)] interactions. The solvent-solvent interactions as observed in said steroidal derivative are rarely found in steroids and such investigations could be important to understand more complicated processes that occur for biomolecules in aqueous solutions.

Keywords

Androstane X-ray diffraction Biological activity Intra- and intermolecular hydrogen bonds Bifurcated hydrogen bonds Solvent–solute interactions Lipinski’s rule 

References

  1. 1.
    Makin HLJ (1975) Biochemistry of steroid hormones. Blackwell Scientific Publications, Oxford, p 4Google Scholar
  2. 2.
    Briggs MJ, Brothern J (1970) Steroid biochemistry and pharmacology. Academic Press, London/New York, p 121Google Scholar
  3. 3.
    Makin HLJ (1975) Biochemistry of steroid hormones. Blackwell Scientific Publications, Oxford, p 70Google Scholar
  4. 4.
    Gower DB, Bicknell DC (1972) Acta Endocr 70:567Google Scholar
  5. 5.
    Makin HLJ (1975) Biochemistry of steroid hormones. Blackwell Scientific Publications, Oxford, p 77Google Scholar
  6. 6.
    Bhavnaish Chand, Malik MA, Singh A (2009) Indian J Biochem Biophys (Communicated)Google Scholar
  7. 7.
    Bhavnaish C, Malik MA, Singh A (2009) Crystallogr Rep (Communicated)Google Scholar
  8. 8.
    Precioux PG, Busetta B, Courseille C, Hospital M (1975) Acta Crystallogr B31:1527Google Scholar
  9. 9.
    Weeks CM, Rohrer DC, Duax WL, Osawa Y (1975) Acta Crystallogr B31:2525Google Scholar
  10. 10.
    Rohrer DC, Duax WL, Osawa Y (1976) Acta Crystallogr B32:2410Google Scholar
  11. 11.
    Precioux PG, Busetta B, Hospital M (1977) Acta Crystallogr B33:563Google Scholar
  12. 12.
    Precioux PG, Busetta B, Hospital M (1977) Acta Crystallogr B33:566Google Scholar
  13. 13.
    Neubert LA, Carmack M, Huffman JC (1977) Acta Crystallogr B33:962Google Scholar
  14. 14.
    Rohrer DC, Strong PD, Duax WL, Segaloff A (1978) Acta Crystallogr B34:2913Google Scholar
  15. 15.
    Duax WL, Rohrer DC, Segaloff A (1982) Acta Crystallogr B38:531Google Scholar
  16. 16.
    De Cowe HJ, Cox PJ, Sim GA (1982) Acta Crystallogr B38:662Google Scholar
  17. 17.
    Cox PJ, Sim GA (1982) Acta Crystallogr B38:1360Google Scholar
  18. 18.
    Weeks CM, Strong PD, Duax WL, Vickery LE (1983) Acta Crystallogr C39:1698Google Scholar
  19. 19.
    Solans X, Piniella JF, Brainso JL, Miravitlles C (1987) Acta Crystallogr C43:2372Google Scholar
  20. 20.
    Danaci S, Kendi E, Mores FG, Behm H, Beurskens PT (1988) Acta Crystallogr C44:1677Google Scholar
  21. 21.
    Michel AG, Reul R, Dewez NM (1989) Acta Crystallogr C45:1760Google Scholar
  22. 22.
    Galdecki Z, Grochulski P, Wawrzak Z (1989) J Cryst Spect Res 19(3):577–587CrossRefGoogle Scholar
  23. 23.
    Cox PJ, Mac Manus SM, Gibb BC, Nowell IW, Howie RA (1990) Acta Crystallogr C46:334Google Scholar
  24. 24.
    Eggleston DS, Lan-Hargest HY (1990) Acta Crystallogr C46:1686Google Scholar
  25. 25.
    Roszak AW, Codding PW (1990) Acta Crystallogr C46:1700Google Scholar
  26. 26.
    Drouin M, Ruel R, Michel AG (1991) Acta Crystallogr C47:1689Google Scholar
  27. 27.
    Meetsma A, Van Leusen D, Van Leusen AM (1993) Acta Crystallogr C49:351Google Scholar
  28. 28.
    Michel AG, Droun Marc (1993) Acta Crystallogr C49:1683Google Scholar
  29. 29.
    Brock CP, Song J (1995) Acta Crystallogr C51:2437Google Scholar
  30. 30.
    Steiner T (1996) Cryst Rev 6:1CrossRefGoogle Scholar
  31. 31.
    Ramos Silva M, Paixao JA, De Almedia MJM, Tavares Da Silva EJ, Melo ML, Campos Neves AS (1996) Acta Crystallogr C52:2892Google Scholar
  32. 32.
    Paixao JA, Ramos Silva M, De Almedia MJM, Tavares Da Silva EJ, Melo ML, Campos Neves AS (1997) Acta Crystallogr C53:347Google Scholar
  33. 33.
    Brunskill APJ, Lalancette RA, Thompson HW (1997) Acta Crystallogr C53:903Google Scholar
  34. 34.
    Andradre LCR, Paixao JA, De Almedia MJM, Tavares Da Silva EJ, Melo ML, Campos Neves AS (1997) Acta Crystallogr C53:938Google Scholar
  35. 35.
    Anthony A, Jaskolski M, Nangia A, Desiraju GR (1998) Acta Crystallogr C54:1894Google Scholar
  36. 36.
    Anthony A, Jaskolski M, Nangia A, Desiraju GR (1998) Acta Crystallogr C54:1898Google Scholar
  37. 37.
    Lazar D, Stankovic S, Sakac M, Penov-Gasic K, Kovacevic R, Medic-Mijacevic L, Pilate T (1998) Acta Crystallogr C54:1965Google Scholar
  38. 38.
    Andrade LCR, Paixao JA, De Almedia MJM, Tavares Da Silva EJ, Melo ML, Campos Neves AS (1999) Acta Crystallogr C55:637Google Scholar
  39. 39.
    Anthony A, Jaskolski M, Nangia A (1999) Acta Crystallogr C55:787Google Scholar
  40. 40.
    Andrade LCR, Paixao JA, De Almedia MJM, Tavares Da Silva EJ, Melo ML, Campos Neves AS (1999) Acta Crystallogr C55:1186Google Scholar
  41. 41.
    Thompson HW, Lalancette RA, Brunskill APJ (1999) Acta Crystallogr C55:1680Google Scholar
  42. 42.
    Andrade LC R, Paixao JA, De Almedia MJM, Tavares Da Silva EJ, Melo ML, Campos Neves AS (1999) Acta Crystallogr C55:2149Google Scholar
  43. 43.
    Vasuki G, Parthasarthi V, Ramamurthi K, Jindal DP, Dubey S (2001) Acta Crystallogr C57:1062Google Scholar
  44. 44.
    Newman JM, Lalancette RA, Thompson HW (2002) Acta Crystallogr C58:o402Google Scholar
  45. 45.
    Hema R, Parthasarthi V, Thamotharan S, Dubey S, Jindal DP (2002) Acta Crystallogr C59:o421Google Scholar
  46. 46.
    Thamotharan S, Parthasarthi V, Gupta R, Jindal DP, Linden A (2002) Acta Crystallogr C58:o727Google Scholar
  47. 47.
    Hema R, Parthasarthi V, Thamotharan S, Dubey S, Jindal DP (2003) Acta Crystallogr C59:o213Google Scholar
  48. 48.
    Lalancette RA, Thompson HW (2003) Acta Crystallogr C59:o274Google Scholar
  49. 49.
    Thamotharan S, Parthasarthi V, Gupta R, Jindal DP, Linden A (2003) Acta Crystallogr C59:o724Google Scholar
  50. 50.
    Paixao JIF, Salvador JAR, Paixao JA, Beja AM, Ramos Silva M, Rocha Gonsalves AM (2004) Acta Crystallogr C60:o72Google Scholar
  51. 51.
    Thamotharan S, Parthasarthi V, Gupta R, Guleria S, Jindal DP, Linden A (2004) Acta Crystallogr C60:o75Google Scholar
  52. 52.
    Thamotharan S, Parthasarthi V, Dubey S, Jindal DP, Linden A (2004) Acta Crystallogr C60:o110Google Scholar
  53. 53.
    Thamotharan S, Parthasarthi V, Gupta R, Jindal DP, Linden A (2004) Acta Crystallogr C60:o158Google Scholar
  54. 54.
    Thamotharan S, Parthasarthi V, Gupta R, Jindal DP, Linden A (2004) Acta Crystallogr C60:o161Google Scholar
  55. 55.
    Paixao JIF, Salvador JAR, Paixao JA, Beja AM, Ramos Silva M, Rocha Gonsalves AM (2004) Acta Crystallogr C60:o630Google Scholar
  56. 56.
    Lazar D, Klisuric O, Stankovic S, Penov-Gasic K, Djurendic E, Kovacevic R (2004) Acta Crystallogr C60:o671Google Scholar
  57. 57.
    Rajnikant V, Dinesh J, Sawhney A, Mousmi B, Gupta BD (2004) J Chem Crystallogr 34(8):523CrossRefGoogle Scholar
  58. 58.
    Andrade LCR, Paixao JA, De Almedia MJM, Fernandes Roleria FM, Travares Da Silva EJ (2005) Acta Crystallogr C61:o131Google Scholar
  59. 59.
    Rajnikant, Dinesh, Mousmi (2005) J Chem Cryst 36(5):283Google Scholar
  60. 60.
    Filimonov DA, Poroikov VV, Borodina Yu, Gloriozova T (1999) J Chem Inf Comput Sci 39:666Google Scholar
  61. 61.
    Poroikov VV, Filimonov DA (2001) Computer-assisted predictions of biological activity in search for and optimization of new drugs. Iridium Press, Moscow, p 149Google Scholar
  62. 62.
    Poroikov VV, Akimov DA, Shabelnikova E, Filimonov DA (2001) SAR and QSAR in Environ Res 12(4):327CrossRefGoogle Scholar
  63. 63.
    Anzali S, Barnickel G, Cezanne B, Krug M (2001) J Med Chem 44:2432CrossRefGoogle Scholar
  64. 64.
    Poroikov VV, Filimonov DA, Ihlenfeldt WD, Gloriozova TA, Lagunin AA, Borodina YV, Stepanchikova AV, Nicklaus MC (2003) J Chem Inf Comput Sci 43:228Google Scholar
  65. 65.
    Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Adv Drug Deliv Rev 23:3CrossRefGoogle Scholar
  66. 66.
    Sutton LE (1965) Tables of interatomic distances and configuration in molecules and ions. Special Publication No. 18. Chemical Society, LondonGoogle Scholar
  67. 67.
    Allen FH, Kennard O, Watson DG, Bramer L, Orpen AG, Taylor R (1987) J Chem Soc Perkin Trans 2:S1–S19Google Scholar
  68. 68.
    Bartell LS, Bonham RA (1960) J Chem Phys 32(3):824CrossRefGoogle Scholar
  69. 69.
    Palenik GJ (1965) Acta Cryst 19:47CrossRefGoogle Scholar
  70. 70.
    Sudralingam M (1966) Acta Crystallogr B21:495CrossRefGoogle Scholar
  71. 71.
    Pletcher J, Sax M (1972) J Am Chem Soc 94:3998CrossRefGoogle Scholar
  72. 72.
    Taylor R, Kennard O (1982) J Am Chem Soc 104:5063CrossRefGoogle Scholar
  73. 73.
    Steiner T, Saenger W (1992) Acta Crystallogr B48:819Google Scholar
  74. 74.
    Steiner T, Saenger W (1992) J Am Chem Soc 114:10146CrossRefGoogle Scholar
  75. 75.
    Steiner T (1996) Cryst Rev 6:7CrossRefGoogle Scholar
  76. 76.
    Jefferey GA (1997) An introduction to hydrogen bonding. Oxford University Press, New York, p 400Google Scholar
  77. 77.
    Steiner T (1998) Acta Crystallogr B54:456Google Scholar
  78. 78.
    Desiraju GR, Steiner T (1999) The weak hydrogen bond in structural chemistry and biology. Oxford University Press Inc, New York, p 66Google Scholar
  79. 79.
    Steiner T (2002) Angew Chem Int Ed Eng 41:48CrossRefGoogle Scholar
  80. 80.
    Olovsson I, Jonsson PG (1976) The hydrogen bond. Recent developments in theory & experiment, vol 2. North Holland, Amsterdam, p 393Google Scholar
  81. 81.
    Desiraju GR (1991) Acc Chem Res 24:270CrossRefGoogle Scholar
  82. 82.
    Bernstein J (1994) In: Burgi HB, Dunitz JD (eds) Structure correlation, vol 2. VCH, Weinheim, p 431Google Scholar
  83. 83.
    Jeffery GA (1999) J Mol Struct 485:293CrossRefGoogle Scholar
  84. 84.
    Desiraju GR, Steiner T (1999) The weak hydrogen bond in structural chemistry and biology. Oxford University Press Inc, New York, p 116Google Scholar
  85. 85.
    Steiner T (2001) Acta Crystallogr C57:775Google Scholar
  86. 86.
    Desiraju GR, Steiner T (1999) The weak hydrogen bond in structural chemistry and biology. Oxford University Press Inc, New York, p 13Google Scholar
  87. 87.
    Rivelino R, Canuto S, Coutinho K (2004) Braz J Phys 34(1):84CrossRefGoogle Scholar
  88. 88.
    Scheiner S (1997) Hydrogen bonding: a theoretical perspective. Oxford University Press Inc, New YorkGoogle Scholar
  89. 89.
    Cramer CJ, Truhlar DG (1999) Chem Rev 99:2161CrossRefGoogle Scholar
  90. 90.
    Kollman P (1993) Chem Rev 93:2395CrossRefGoogle Scholar
  91. 91.
    Baldridge KK, Jonas V, Bain AD (2000) J Chem Phys 113(17):7519CrossRefGoogle Scholar
  92. 92.
    Allen MP, Tildesley DJ (1987) Computer simulation of liquids. Oxford University Press, New YorkGoogle Scholar
  93. 93.
    Coutinho K, Canuto S, Zerner MC (2000) J Chem Phys 112:9874CrossRefGoogle Scholar
  94. 94.
    Canuto S, Coutinho K, Trzesniak D (2002) Adv Quantum Chem 41:161CrossRefGoogle Scholar
  95. 95.
    Jedlovszky P, Turi L (1997) J Phys Chem B101:5429Google Scholar
  96. 96.
    Tezuka T, Nakagawa M, Yokoi K, Nagawa Y, Yamagaki YT, Nakanishi H (1997) Tetrahedron Lett 38(24):4223CrossRefGoogle Scholar
  97. 97.
    Davidson MG, Lamb S (1997) Polyhedron 16:4393CrossRefGoogle Scholar
  98. 98.
    Klebe G, Mietzner T, Weber F (1999) J Comput-Aided Mol Des 13:35CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of PhysicsPost-Graduate College (Boys)UdhampurIndia
  2. 2.Department of PhysicsAmar Singh CollegeSrinagarIndia

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