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N-formylpyrazolines and N-benzoylpyrazolines as potential inhibitors cathepsin L

Department of Chemistry, Kurukshetra University, Kurukshetra-136119, India

Elevated levels of cathepsins implicated in cancer, inflammation and number of degenerative diseases emphasize the investigation of potential inhibitors in search for novel chemotherapeutic agents with better efficacy. Along with other cathepsins, cathepsin L has emerged out as a potential drug target in these diseased conditions. In the present study, we have assayed the inhibitory potency of two structurally related series of substituted N-formylpyrazolines and N-benzoylpyrazolines as inhibitors to cathepsin L. SAR studies show that N-formylpyrazolines were better inhibitors than N-benzoylpyrazolines. The most potent inhibitors among the two series were nitro substituted compounds 1i and 2i with Kvalues of ~6.4 × 10−10 and 5.7 × 10−9 M for cathepsin L, respectively. The inhibitory potential of the compounds have been found comparative to the specific inhibitor, leupeptin. Docking experiments showing interaction between N-formylpyrazolines, N-benzoylpyrazolines and cathepsin L active site also provided useful insights.
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Keywords N-formylpyrazolines; N-benzoylpyrazolines; cathepsin L inhibitors; endogenous proteolysis

Citation: S. Garg, N. Raghav. N-formylpyrazolines and N-benzoylpyrazolines as potential inhibitors cathepsin L. AIMS Molecular Science, 2016, 3(3): 454-465. doi: 10.3934/molsci.2016.3.454


  • 1. Kim SH, Lee E, Baek KH, et al. (2013) Chalcones, inhibitors for topoisomerase I and cathepsin B and L, as potential anti-cancer agents. Bioorg Med Chem Lett 23: 3320-3324.    
  • 2. Caracelli I, Vega-Teijido M, Zukerman-Schpector J, et al. (2012) A tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation. J Mol Struct 1013: 11-18.
  • 3. Raghav N, Singh M (2014) Acyl hydrazides and triazoles as novel inhibitors of mammalian Cathepsin B and Cathepsin H. Eur J Med Chem 77: 231-242.    
  • 4. Raghav N, Singh M (2014) Design, synthesis and docking studies of bischalcones based quinazoline-2(1H)-ones and quinazoline-2(1H)-thiones derivatives as novel inhibitors ofCathepsin B and Cathepsin H. Eur J Pharm Sci 541: 28-39.
  • 5. Raghav N, Ravish I (2015) SAR studies of differently functionalized 4’-phenylchalcone based compounds as inhibitors of Cathepsins B, H and L. RSC Adv 5: 50440-50453.    
  • 6. Raghav N, Kaur R (2014) Synthesis and evaluation of some semicarbazone and thiosemicarbazone based cathepsin B inhibitors. Med Chem Res 23: 4669-4679.    
  • 7. Raghav N, Kaur R (2015) Chalcones, semicarbazones and pyrazolines as inhibitors of cathepsins B, H and L. Int J Biol Macromol 80: 710-724.    
  • 8. Jainey PJ, Bhat IK (2012) Antitumor, analgesic, and anti-inflammatory activities of synthesized novel pyrazolines. J Young Pharm 4: 82-87.    
  • 9. Bandgar BP, Adsul LK, Chavan HV, et al. (2012) Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents. Bioorg Med Chem Lett 22: 5839-5844.    
  • 10. Fioravanti R, Bolasco A, Mann F, et al. (2010) Synthesis and biological evaluation of N-substituted-3,5-diphenyl-2-pyrazoline derivatives as cyclooxygenase (COX-2) inhibitors. Eur J Med Chem 45: 6135-6138.    
  • 11. Abdalla MM, Al-Omar MA, Bhat MA, et al. (2012) Steroidal pyrazolines evaluated as aromatase and quinone reductase-2 inhibitors for chemoprevention of cancer. Int J Biol Macromol 50: 1127-1132.    
  • 12. Ivanyi Z, Szabo N, Huber J, et al. (2012) Synthesis of D-ring-substituted (5'R)- and (5'S)-17β-pyrazolinylandrostene epimers and comparison of their potential anticancer activities. Steroids 77: 566-574.    
  • 13. Banday AH, Mir BP, Lone IH, et al. (2010) Studies on novel D-ring substituted steroidal pyrazolines as potential anticancer agents. Steroids 75: 805-809.    
  • 14. Ismaeil ZH, Soliman FMA, Abd-El Monem SH (2011) Synthesis, Antimicrobial and Antitumor Activity of Some 3, 5-Diaryl and 1, 3, 5-Triaryl-2-Pyrazoline Derivatives. J Am Sci 7: 756-767.
  • 15. Manna F, Chimenti F, Fioravanti R, et al. (2005) Synthesis of some pyrazole derivatives and preliminary investigation of their affinity binding to P-glycoprotein. Bioorg Med Chem Lett 15: 4632-4635.    
  • 16. Congiu C, Onnis V, Vesci L, et al. (2010) Synthesis and in vitro antitumor activity of new 4,5-dihydropyrazole derivatives. Bioorg Med Chem 18: 6238-6248.    
  • 17. Garg S, Raghav N (2014) N-formylpyrazolines and N-benzoylpyrazolines as novel inhibitors of mammalian cathepsin B and cathepsin H. J Bioorg Chem 57: 43-50.    
  • 18. Otto HH, Schirmeister T (1997) Cysteine Proteases and Their Inhibitors. Chem Rev 97: 133-171.    
  • 19. Turk V, Kos J, Turk B (2004) Cysteine cathepsins (proteases) - on the main stage of cancer? Cancer Cell 5: 409-410.    
  • 20. Dana D, Davalos AR, De S, et al. (2013) Development of cell-active non-peptidyl inhibitors of cysteine cathepsin. Bioorg Med Chem 21: 2975-2987.    
  • 21. Schenker P, Alfarano P, Kolb P (2008) A double-headed cathepsin B inhibitor devoid of warhead. Protein Sci 17: 2145-2155.    
  • 22. Garg S, Raghav N (2016) 2, 5-diaryloxadiazoles and their precursors as novel inhibitors of cathepsinsB, H and L. J Bioorg Chem 67: 64-74.    
  • 23. Garg S, Raghav N (2015) Inhibitory potential of some chalcones on Cathepsin B, H and L. RSC Adv 5: 72937-72949.
  • 24. Raghav N, Singh M (2014) Design, synthesis and docking studies of bischalcones based quinazoline-2(1H)-ones and quinazoline-2(1H)-thiones derivatives as novel inhibitors of cathepsin B and cathepsin H. Eur J Pharm Sci 54: 28-39.    
  • 25. Garg S, Raghav N (2014) SAR studies of o-hydroxychalcones and their cyclized analogs and study them as novel inhibitors of cathepsin B and cathepsin H. Eur J Pharm Sci 60: 55-63.    
  • 26. Raghav N, Singh M, Garg S, et al. (2015) Ion exchangers: a useful tool for separation and simultaneous purification of lysosomal cysteine proteinases, cathepsins B, H and L. Int J Pharm Sci Res 6: 2944-2949.
  • 27. Kamboj RC, Pal S, Raghav N, et al. (1993) Selective colorimetric assay forcathepsin L using Z-Phe-Arg-4-methoxy-β-naphthylamide. Biochimie 75: 873.    
  • 28. Chowdhary SF, Joseph L, Kumar S, et al. (2008) Exploring inhibitor binding at the S’ subsites of cathepsin L. J Med Chem 51: 1361-1368.
  • 29. Morrison JF (1969) Kinetics of the reversible inhibition of enzyme-catalysed reactions by tight-binding inhibitors. Biochim Biophys Acta 185: 269-286.    
  • 30. Berger A, Schechter I (1967) On the size of active site in proteases. I. Papain. Biochem Biophys Res Commun 27: 157-162.    
  • 31. Garg S, Raghav N (2016) 2’-hydroxychalcones and their cyclized derivatives as cathepsin L inhibitors. BAOJ Can Res Ther 2: 1-6.


This article has been cited by

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