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QSAR studies on diclofenac analogues as potent cyclooxygenase inhibitors using CoMFA and CoMSIA

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Abstract

A series of 36 diclofenac analogues were analyzed for structure–activity relationship using CoMFA and CoMSIA. The CoMFA-based equation gave q 2 = 0.625 and r 2 = 0.973 compared to q 2 = 0.773 and r 2 = 0.959 for CoMSIA. The CoMSIA and CoMFA contours were analyzed and the structural features contributing to the enhancement of activity were identified. Based on the results obtained from these analysis two compounds were designed which show enhancement in activity compared to the parent compound. The new leads are predicted to be non-toxic through computational methods.

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References

  • Bandgar BP, Sarangdhar RJ, Ahamed FA, Viswakarma S (2011) Synthesis, characterization, and biological evaluation of novel diclofenac prodrugs. J Med Chem 54(5):1202–1210

    Article  CAS  PubMed  Google Scholar 

  • Bush B, Nachbar R Jr (1993) Sample-distance partial least squares: PLS optimized for many variables, with application to CoMFA. J Computer-Aided Mol Des 7(5):587–619

    Article  CAS  Google Scholar 

  • Chan FKL, Lanas A, Scheiman J, Berger MF, Nguyen H, Goldstein JL (2010) Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial. Lancet 376(9736):173–179

    Article  CAS  PubMed  Google Scholar 

  • Cox PJ (1993) HyperChem—release 2 for windows 1992 : AUTODESK Ltd., cross lanes, Guildford, Surrey, U.K. £500.00 (Educational users), £2000.00 (other users). Talanta 40(6):954–955. doi:10.1016/0039-9140(93)80068-3

    Article  Google Scholar 

  • Cryer B (2005) NSAID-associated deaths: the rise and fall of NSAID-associated GI mortality. Am J Gastroenterol 100(8):1694–1695

    Article  CAS  PubMed  Google Scholar 

  • Ferrara P, Gohlke H, Price DJ, Klebe G, Brooks CL (2004) Assessing scoring functions for protein–ligand interactions. J Med Chem 47(12):3032–3047

    Article  CAS  PubMed  Google Scholar 

  • Ferreira SH, Moncada S, Vane JR (1997) Prostaglandins and the mechanism of analgesia produced by aspirin-like drugs. Br J Pharmacol 120(S1):401–412. doi:10.1111/j.1476-5381.1997.tb06823

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hansch C, Fujita T (1964) P–σ–π analysis. A method for the correlation of biological activity and chemical structure. J Am Chem Soc 86(8):1616–1626

    Article  CAS  Google Scholar 

  • Huang M, Yang D-Y, Shang Z, Zou J, Yu Q (2002) 3D-QSAR studies on 4-hydroxyphenylpyruvate dioxygenase inhibitors by comparative molecular field analysis (CoMFA). Bioorg Med Chem Lett 12(17):2271–2275. doi:10.1016/s0960-894x(02)00432-8

    Article  CAS  PubMed  Google Scholar 

  • James MW, Hawkey CJ (2003) Assessment of non-steroidal anti-inflammatory drug (NSAID) damage in the human gastrointestinal tract. Br J Clin Pharmacol 56(2):146–155

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Klebe G, Abraham U, Mietzner T (1994) Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J Med Chem 37(24):4130–4146. doi:10.1021/jm00050a010

    Article  CAS  PubMed  Google Scholar 

  • Lipinski CA (2000) Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 44(1):235–249

    Article  CAS  PubMed  Google Scholar 

  • McKenna F (1993) Efficacy of diclofenac/misoprostol vs diclofenac in the treatment of ankylosing spondylitis. Drugs 45(1):24–30

    Article  PubMed  Google Scholar 

  • Moser P, Sallmann A, Wiesenberg I (1990) Synthesis and quantitative structure-activity relationships of diclofenac analogs. J Med Chem 33(9):2358–2368

    Article  CAS  PubMed  Google Scholar 

  • Næsdal J, Brown K (2006) NSAID-associated adverse effects and acid control AIDS to prevent them: a review of current treatment options. Drug Safety 29(2):119–132

    Article  PubMed  Google Scholar 

  • Oprea TI, Waller CL, Marshall GR (1994) Three-dimensional quantitative structure-activity relationship of human immunodeficiency virus (I) protease inhibitors. 2. Predictive power using limited exploration of alternate binding modes. J Med Chem 37(14):2206–2215

    Article  CAS  PubMed  Google Scholar 

  • Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S, Graneto MJ, Lee LF, Malecha JW, Miyashiro JM, Rogers RS, Rogier DJ, Yu SS, Anderson GD, Burton EG, Cogburn JN, Gregory SA, Koboldt CM, Perkins WE, Seibert K, Veenhuizen AW, Zhang YY, Isakson PC (1997) Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, celecoxib). J Med Chem 40(9):1347–1365

    Article  CAS  PubMed  Google Scholar 

  • Picot D, Loll PJ, Garavito RM (1994) The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1. Nature 367(6460):243–249

    Article  CAS  PubMed  Google Scholar 

  • Talley JJ, Brown DL, Carter JS, Graneto MJ, Koboldt CM, Masferrer JL, Perkins WE, Rogers RS, Shaffer AF, Zhang YY, Zweifel BS, Seibert K (2000) 4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. J Med Chem 43(5):775–777

    Article  CAS  PubMed  Google Scholar 

  • Temiz-Arpaci O, Tekiner-Gulbas B, Yildiz I, Aki-Sener E, Yalcin I (2005) 3D-QSAR analysis on benzazole derivatives as eukaryotic topoisomerase II inhibitors by using comparative molecular field analysis method. Bioorg Med Chem 13(23):6354–6359

    Article  CAS  PubMed  Google Scholar 

  • Vedani A, Dobler M, Smieško M (2012) VirtualToxLab—a platform for estimating the toxic potential of drugs, chemicals and natural products. Toxicol Appl Pharmacol 261(2):142–153

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Sun P (2007) 3D-QSAR Study of Potent Inhibitors of Phosphodiesterase-4 Using a CoMFA Approach. Int J Mol Sci 8(7):714–722

    Article  PubMed Central  CAS  Google Scholar 

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Acknowledgments

We dedicate this paper to our beloved founder Chancellor Bhagawan Sri Sathya Sai Baba. We thank Prof.Mukesh Doble, IIT Madras for allowing us to use Tripos SYBYL and the team of easy QSAR for their free software.

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Authors and Affiliations

  1. Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Vidyagiri, Prasanthi Nilayam, Puttaparthi, 515134, Andhra Pradesh, India

    K. Arvind & S. S. Rajan

  2. Sankar Foundation Research Institute, Sai Madhava Nagar, Naiduthota, Vepagunta, Visakhapatnam, 530047, India

    K. Anand Solomon

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  1. K. Arvind
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  2. K. Anand Solomon
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  3. S. S. Rajan
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Correspondence to S. S. Rajan.

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Arvind, K., Solomon, K.A. & Rajan, S.S. QSAR studies on diclofenac analogues as potent cyclooxygenase inhibitors using CoMFA and CoMSIA. Med Chem Res 23, 1789–1796 (2014). https://doi.org/10.1007/s00044-013-0771-5

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  • DOI: https://doi.org/10.1007/s00044-013-0771-5

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