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Synthesis and biological evaluation of cationic fullerene quinazolinone conjugates and their binding mode with modeled Mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase enzyme

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Abstract

The present work reports a series of novel cationic fullerene derivatives bearing a substituted-quinazolinone moiety as a side arm. Fullerene-quinazolinone conjugates synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinone were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H 37 Rv strain). All the compounds exhibited significant activity with the most effective having MIC in the range of 1.562–3.125 μg/mL. Compound 9f exhibited good biological activity compared to standard drugs. We developed a computational strategy based on the modeled M. tuberculosis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) using homology modeling techniques and studied its binding pattern with synthesized fullerene derivatives. We then explored the surface geometry of the protein to place the cage adjacent to the active site while optimizing its quinazolinone side arm to establish H bonding with active site residues.

Cationic derivatives of fullerene-quinazolinone conjugates and their docked poses in Modelied M. tuberculosis HGPRT enzyme

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Abbreviations

AMBER:

Assisted model building with energy refinement

BCG:

Bacillus Calmette-Guérin

BLAST:

Basic local alignment search tool

CSP:

Constraint space programming

E value:

Expected value

EC:

Enzyme classification

ExPASy:

Expert protein analysis system

GA:

Genetic algorithm

GB:

Generalized born

HGPRT:

Hypoxanthine-guanine phosphoribosyltransferase

MDR-TB:

Multi drug resistance tuberculosis

PB:

Poisson-boltzmann

PEARLS:

Program of energetic analysis of receptor ligand systems

PPi :

Inorganic pyrophosphate

PRPP:

α-D-phosphoribosyl-1-pyrophosphate

PRPP:

Phosphoribosyl pyrophosphate

PRT:

Phosphoribosyl transferase

QMEAN:

Qualitative model energy analysis

RCSB PDB:

Research collaborative for structural bioinformatics protein data bank

SAVES:

Structural analysis and verification server

SCRs:

Structurally conserved regions

TB:

Tuberculosis

TMS:

Tetra methyl silane

References

  1. WHO (2011–2012) Global facts on tuberculosis. http://www.who.int/tb

  2. Butler D (2000) Nature 406:670–672

    Article  CAS  Google Scholar 

  3. Ahmad SME, Vinsova J, Kratky M, Ngy S, K’ung Z (2010) Nova Science Pub Incorporated 1–328

  4. Zhang Y, Young D (1994) J Antimicrob Chemother 34:313–319

    Article  CAS  Google Scholar 

  5. Kumar SP, Srinivasan P, Patel SK, Jasrai YT, Pandya HA (2011) J Adv Bioinform Appl 2:142–148

    CAS  Google Scholar 

  6. Kumar A, Menon SK (2009) Eur J Med Chem 44:2178–2183

    Article  CAS  Google Scholar 

  7. Kumar A, Patel G, Menon SK (2009) Chem Biol Drug Des 73:553–557

    Article  CAS  Google Scholar 

  8. Dugan LL, Turetsky DM, Du C, Lobner D, Wheeler M, Almli CR, Shen CKF, Luh TY, Choi DW, Lin TS (1997) Proc Natl Acad Sci USA 94:9434–9439

    Article  CAS  Google Scholar 

  9. Gharbi N, Pressac M, Hadchouel M, Szwarc H, Wilson SR, Moussa F (2005) Nano Lett 5:2578–2585

    Article  CAS  Google Scholar 

  10. Zhou Z, Lenk RP, Dellinger A, Wilson SR, Sadler R, Kepley CL (2010) Bioconjug Chem 21:1656–1661

    Article  CAS  Google Scholar 

  11. Kumar A, Rao MV, Menon SK (2009) Tetrahedron Lett 50:6526–6530

    Article  CAS  Google Scholar 

  12. Zhou C, Liu Q, Xu W, Wang C, Fang X (2011) Chem Commun 47:2982–2984

    Article  CAS  Google Scholar 

  13. Durdagi S, Supuran CT, Strom TA, Doostdar N, Kumar MK, Barron AR, Mavromoustakos T, Papadopoulos MG (2009) J Chem Inf Model 49:1139–1143

    Article  CAS  Google Scholar 

  14. Marcorin GL, Da Ros T, Castellano S, Stefancich G, Bonin I, Miertus S, Prato M (2000) Org Lett 2:3955–3958

    Article  CAS  Google Scholar 

  15. Kumar A, Patel B, Patel G, Menon SK (2010) Fullerenes Nanotubes and Carbon Nanostructures 18:186–197

    Article  CAS  Google Scholar 

  16. Maeda Mamiya R, Noiri E, Isobe H, Nakanishi W, Okamoto K, Doi K, Sugaya T, Izumi T, Homma T, Nakamura E (2010) Proc Natl Acad Sci USA 107:5339–5344

    Article  CAS  Google Scholar 

  17. Zakharian TY, Seryshev A, Sitharaman B, Gilbert BE, Knight V, Wilson LJ (2005) J Am Chem Soc 127:12508–12509

    Article  CAS  Google Scholar 

  18. Foley S, Crowley C, Smaihi M, Bonfils C, Erlanger BF, Seta P, Larroque C (2002) Biochem Biophys Res Commun 294:116–119

    Article  CAS  Google Scholar 

  19. Lakhan R, Rai BJ (1987) J Chem Eng Data 32:384–386

    Article  CAS  Google Scholar 

  20. Baba A, Kawamura N, Makino H, Ohta Y, Taketomi S, Sohda T (1996) J Med Chem 39:5176–5182

    Article  CAS  Google Scholar 

  21. Kumar A, Sharma P, Kumari P, Lal Kalal B (2011) Med Chem Lett 21:4353–4357

    Article  CAS  Google Scholar 

  22. Kuneš J, Bažant J, Pour M, Waisser K, Šlosárek M, Janota J (2000) Il Farmaco 55:725–729

    Article  Google Scholar 

  23. Waisser K, Gregor J, Dostál H, Kuneš J, Kubicová L, Klimešová V, Kaustová J (2001) Il Farmaco 56:803–807

    Article  CAS  Google Scholar 

  24. Colotta V, Catarzi D, Varano F, Lenzi O, Filacchioni G, Costagli C, Galli A, Ghelardini C, Galeotti N, Gratteri P, Sgrignani J, Deflorian F, Moro S (2006) J Med Chem 49:6015–6026

    Article  CAS  Google Scholar 

  25. Ducati RG, Basso LA, Santos DS, de Azevedo WF Jr (2010) Bioorg Med Chem 18:4769–4774

    Article  CAS  Google Scholar 

  26. de Azevedo WF Jr (2011) Curr Med Chem 18:1353–1366

    Article  Google Scholar 

  27. Dias R, Timmers LF, Caceres RA, de Azevedo WF Jr (2008) Curr Drug Targets 9:1062–1070

    Article  CAS  Google Scholar 

  28. Caceres RA, Timmers LF, Ducati RG, da Silva DO, Basso LA, de Azevedo WF Jr, Santos DS (2012) Biochimie 94:155–165

    Article  CAS  Google Scholar 

  29. de Azevedo WF Jr (2011) Curr Med Chem 18:1255–1257

    Article  Google Scholar 

  30. Tang YJ, Ashcroft JM, Chen D, Min G, Kim CH, Murkhejee B, Larabell C, Keasling JD, Chen FF (2007) Nano Lett 7:754–760

    Article  CAS  Google Scholar 

  31. Freymann DM, Wenck MA, Engel JC, Feng J, Focia PJ, Eakin AE, Craig SP (2000) Chem BioI 7:957–968

    Article  CAS  Google Scholar 

  32. Gupta SK, Dhawan A, Shanker R (2011) J Biomed Nanotechnol 7:91–92

    Article  CAS  Google Scholar 

  33. Consortium TU (2012) Nucleic Acids Res 40:D71–D75

    Article  Google Scholar 

  34. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) J Mol Biol 215:403–410

    CAS  Google Scholar 

  35. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) Nucleic Acids Res 28:235–242

    Article  CAS  Google Scholar 

  36. Arnold K, Bordoli L, Kopp J, Schwede T (2006) Bioinformatics 22:195–201

    Article  CAS  Google Scholar 

  37. Ward JJ, Sodhi JS, McGuffin LJ, Buxton BF, Jones DT (2004) J Mol Biol 337:635–645

    Article  CAS  Google Scholar 

  38. Lindorff Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, Shaw DE (2010) Funct Bioinf 78:1950–1958

    CAS  Google Scholar 

  39. Ramachandran GN, Ramakrishnan C, Sasisekharan V (1963) J Mol Biol 7:95–99

    Article  CAS  Google Scholar 

  40. Benkert P, Tosatto SCE, Schomburg D (2008) Proteins Struct Funct Bioinf 71:261–277

    Article  CAS  Google Scholar 

  41. Craig SP, Eakin AE (2000) J Biol Chem 275:20231–20234

    Article  CAS  Google Scholar 

  42. Chen Q, You D, Liang Y, Su X, Gu X, Luo M, Zheng X (2007) FEBS J 274:4408–4415

    Article  CAS  Google Scholar 

  43. Gordon JC, Myers JB, Folta T, Shoja V, Heath LS, Onufriev A (2005) Nucleic Acids Res 33:W368–W371

    Article  CAS  Google Scholar 

  44. Laurie ATR, Jackson RM (2005) Bioinformatics 21:1908–1916

    Article  CAS  Google Scholar 

  45. Acton A, Banck M, Bréfort J, Cruz M, Curtis D, Hassinen T, Heikkilä V, Hutchison G, Huuskonen J, Jensen J, Liboska R, Rowley C (2000) Chemical 2.00. Department of Chemistry, University of Kuopio, Kuopio, Finland, http://www.uku.fi/~thassine/projects/ghemical/

  46. Wolf LK (2009) Chem Eng News Arch 87:48

    Google Scholar 

  47. Yang JM, Chen CC (2004) Proteins Struct Funct Bioinf 55:288–304

    Article  CAS  Google Scholar 

  48. Han LY, Lin HH, Li ZR, Zheng CJ, Cao ZW, Xie B, Chen YZ (2005) J Chem Inf Model 46:445–450

    Article  Google Scholar 

  49. Armarego WLF, Chai CLL (2009) Purification of laboratory chemicals. Butterworth-Heinemann, Burlington, MA

  50. Maggini M, Scorrano G, Prato M (1993) J Am Chem Soc 115:9798–9799

    Article  CAS  Google Scholar 

  51. Rather BA, Raj T, Reddy A, Ishar MPS, Sivakumar S, Paneerselvam P (2010) Arch Pharm 343:108–113

    CAS  Google Scholar 

  52. Alagarsamy V, Muruganantham G, Venkateshaperumal R (2003) Biol Pharm Bull 26:1711–1714

    Article  CAS  Google Scholar 

  53. Lyon DY, Adams LK, Falkner JC, Alvarez PJ (2006) J Environ Sci Technol 40:4360–4366

    Article  CAS  Google Scholar 

  54. Anargyros P, Astill DS, Lim IS (1990) J Clin Microbiol 28:1288–1291

    CAS  Google Scholar 

  55. Scott WRP, Hünenberger PH, Tironi IG, Mark AE, Billeter SR, Fennen J, Torda AE, Huber T, Krüger P, van Gunsteren WF (1999) J Phys Chem A 103:3596–3607

    Article  CAS  Google Scholar 

  56. Structural Analysis and Verification Server, NIH-MBI Laboratory for Structural Genomics and Proteomics (http://nihserver.mbi.ucla.edu/SAVES/). Structural Analysis and Verification Server, NIH-MBI Laboratory for Structural Genomics and Proteomics (http://nihserver.mbi.ucla.edu/SAVES/)

  57. Pearlman DA, Case DA, Caldwell JW, Ross WS, Cheatham TE III, DeBolt S, Ferguson D, Seibel G, Kollman P (1995) Comput Phys Commun 91:1–41

    Article  CAS  Google Scholar 

  58. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Comput Phys Commun 25:1157–1174

    CAS  Google Scholar 

Download references

Acknowledgments

M.B.P. thanks the University Grants Commission, New Delhi, India for generous support in the form of a Junior Research Fellowship. S.P.K. and N.N.V. acknowledge generous support from DST, New Delhi in the form of Innovation in Science Pursuit for Inspired Research (INSPIRE) Fellowships.

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Authors and Affiliations

  1. Department of Chemistry, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India

    Manishkumar B. Patel, Nikunj N. Valand & Shobhana K. Menon

  2. Department of Bioinformatics, Applied Botany Centre (ABC), University School of Sciences, Ahmedabad, Gujarat, 380009, India

    Sivakumar Prasanth Kumar & Yogesh T. Jasrai

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  1. Manishkumar B. Patel
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Correspondence to Shobhana K. Menon.

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Patel, M.B., Kumar, S.P., Valand, N.N. et al. Synthesis and biological evaluation of cationic fullerene quinazolinone conjugates and their binding mode with modeled Mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase enzyme. J Mol Model 19, 3201–3217 (2013). https://doi.org/10.1007/s00894-013-1820-1

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  • DOI: https://doi.org/10.1007/s00894-013-1820-1

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