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A comparison of crystallographic and DFT optimized geometries on two taxane diterpenoids and docking studies with phospholipase A2

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Abstract

Structure optimization of two taxane diterpenoids I and II has been carried out using GAUSSIAN03 program with B3LYP/6-31G** basis set. The structures were fully optimized without any geometric constraints. Coordinates found in crystallographic study were used as input to the GAUSSIAN. The results show that the conformations of taxoid cores are almost same as were observed from crystallography, while the conformations of the substituents are slightly different. Thus, taxoid cores are robust enough to maintain their conformations in gaseous state while the conformations of substituents may vary depending upon the reaction condition. To understand the mode of binding, the docking studies of both compounds have been carried out with Russell’s viper phospholipase A2 (vPLA2) as target using induced fit docking. The docking results show that regarding the interactions and energy for indomethacin binding with vPLA2, compound I shows the best results.

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References

  • Appendino G (1993) Antimicrobial activity of the heartwood of Taxus baccata. Fitoterapia 64(suppl l):5–25

    Google Scholar 

  • Appendino G, Gariboldi P, Gabetta B, Pace R, Bombardelli E, Viterbo D (1992) 14β-hydroxy-10-deacetyl baccatin III, a new taxane from Himalayan yew (Taxus wallichiana Zucc). J Chem Soc Perkin Trans I:2925–2930

    Article  Google Scholar 

  • Broughton HB (2000) A Method for including protein flexibility in protein-ligand docking: Improving tools for database mining and virtual screening. J Mol Graph Model 18:247–257

    Article  PubMed  CAS  Google Scholar 

  • Chattopadhyay SK, Sharma RP, Appendino G, Gariboldi P (1995) A rearranged taxane from the Himalayan yew. Phytochemistry 39:869–870

    Article  CAS  Google Scholar 

  • Chattopadhyay SK, Sharon A, Yadava U, Srivastava S, Mehta VK, Maulik PR (2001) A taxane diterpenoid from the needles of Taxus wallichiana. Acta Cryst E57:o1158–o1160

    CAS  Google Scholar 

  • Chattopadhyay SK, Sharon A, Yadava U, Srivastava S, Mehta VK, Maulik PR (2002) A taxane diterpenoid from the heartwood of Taxus wallichiana. Acta Cryst E58:o154–o155

    CAS  Google Scholar 

  • Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Vreven JT, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2003) GAUSSIAN 03, Revision B.04, Gaussian, Inc., Pittsburgh

  • Glide (2010) Version 5.6. Schrodinger, LLC, New York, NY

  • Hartzell H Jr (1991) The yew tree: a thousand whispers. Hulogosi, Eugene, p 64

    Google Scholar 

  • Jorgenson WL, Maxwell DS, Tirado-Rives J (1996) Development and testing of the OPLS all atom force field on conformational energetic and properties of organic liquids. J Am Chem Soc 118:11225–11236

    Article  Google Scholar 

  • Krussmann G (1983) Handbuch der Nadelgeholze. Paul Parey, Berlin and Hamburg, p 332

    Google Scholar 

  • Mastropaolo D, Camerman A, Luo Y, Brayer GD, Camerman A (1995) Crystal and molecular structure of paclitaxel (taxol). Proc Natl Acad Sci USA 92:6920–6924

    Article  PubMed  CAS  Google Scholar 

  • Moitessier N, Therrien E, Henessian S (2006) A method for induced fit docking scoring and ranking of flexible ligands. Application to peptidic and pseudopeptidic β-secretase (BACE 1) inhibitors. J Med Chem 49:5885–5894

    Article  PubMed  CAS  Google Scholar 

  • Parmar VS, Vardhan A, Taneja P, Sinha R, Patnaik GK, Tripathi SC, Boll PM, Larsen S (1991) Absolute configuration of epirhododendrin and (−)–rhododendrin [=(−)–betuligenol] and X-ray crystal and molecular structure of rhododendron [=betuloside] a hepatoprotective constituent of Taxus baccata. J Chem Soc Perkin Trans 1:2687–2690

    Article  Google Scholar 

  • Pouvelle B, Farley PJ, Long CA, Taraschi TF (1994) Taxol arrests the development of blood stage Plasmodium falciparum, invitro and Plasmodium chabaudi adami in malaria infected mice. J Clin Invest 94:413–417

    Article  PubMed  CAS  Google Scholar 

  • Schiff PB, Fant J, Horwitz SB (1979) Promotion of microtubule assembly in vitro by taxol. Nature 277:665–669

    Article  PubMed  CAS  Google Scholar 

  • Sherman W, Day T, Jacobson MP, Friesner RA, Farid R (2006) Novel procedure for modelling ligand/receptor induced fit effects. J Med Chem 49:534–553

    Article  PubMed  CAS  Google Scholar 

  • Singh N, Kumar RP, Kumar S, Sharma S, Mir R, Kaur P, Srinivasan A, Singh TP (2009) Simultaneous inhibition of anti-coagulation and inflammation: crystal structure of phospholipase A2 complexed with indomethacin at 1.4  Å resolution reveals the presence of the new common ligand-binding site. J Mol Recog 22(6):437–445

    Article  CAS  Google Scholar 

  • Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of pacific yew. Science 260:214–216

    Article  PubMed  CAS  Google Scholar 

  • Taylor RD, Jewsbury PJ, Essex JW (2002) A review of protein small molecule docking methods. J Comp Aided Mol Des 16:151–166

    Article  CAS  Google Scholar 

  • Vohora SB, Kumar I (1971) Studies on Taxus baccata—I, preliminary phytochemical and behavioral investigations. Planta Med 20:100–107

    Article  PubMed  CAS  Google Scholar 

  • Vohora SB, Kumar I, Shah SA, Khan MSY (1980) Effect of biflavonoids of Taxus baccata on the central nervous system. Indian J Med Res 71:815–820

    PubMed  CAS  Google Scholar 

  • Vosco SH, Wilk L, Nusair M (1980) Accurate spin dependent electron liquid correlation energies for local spin density calculations: a critical analysis. Can J Phys 58:1200–1211

    Article  Google Scholar 

  • Zhang LU, Gallicchio E, Friesner RA, Levy RM (2001) Solvent models for protein ligand binding: comparison of implicit solvent poisson and surface generalized born models with explicit solvent simulations. J Comp Chem 22:591–607

    Article  CAS  Google Scholar 

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Acknowledgments

U. Yadava is thankful to DST, New Delhi for financial assistance through SERC Fast Track Scheme for Young Scientists (Ref No. SR/FT/CS-78/2010). Authors are also grateful toward Prof. D. Velmurugan, Centre for Advanced Studies in Crystallography and Biophysics, Madras University, Chennai for his valuable suggestions.

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Authors and Affiliations

  1. Department of Physics, DDU Gorakhpur University, Gorakhpur, 273009, India

    Umesh Yadava & Mihir Roychoudhury

  2. Department of Physics, St. Andrews College, Gorakhpur, 273001, India

    Hariom Gupta

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  1. Umesh Yadava
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  2. Hariom Gupta
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  3. Mihir Roychoudhury
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Correspondence to Umesh Yadava.

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Yadava, U., Gupta, H. & Roychoudhury, M. A comparison of crystallographic and DFT optimized geometries on two taxane diterpenoids and docking studies with phospholipase A2. Med Chem Res 21, 2162–2168 (2012). https://doi.org/10.1007/s00044-011-9724-z

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