Medicinal Chemistry Research

, Volume 21, Issue 8, pp 2012–2022 | Cite as

Antimicrobial, analgesic, DPPH scavenging activities and molecular docking study of some 1,3,5-triaryl-2-pyrazolines

  • Seranthimata Samshuddin
  • Badiadka Narayana
  • Balladka Kunhanna Sarojini
  • Mahmud Tareq Hassan Khan
  • Hemmige S. Yathirajan
  • Chenna Govindaraju Darshan Raj
  • Ramappa Raghavendra
Original Research

Abstract

A series of 1,3,5-triaryl-2-pyrazolines 2ag were synthesized by the reaction of 4,4′-disubstituted chalcone with phenyl hydrazine. All these compounds were characterized by NMR, IR and mass spectral and single crystal XRD data. All the synthesized products were screened for their in vitro antimicrobial, analgesic and antioxidant properties. The docking studies were carried out for these compounds against the active site of methionyl-tRNA synthetase (metRS). Some of the tested compounds exhibited significant antimicrobial, analgesic, DPPH scavenging activities and molecular binding.

Keywords

Analgesic Antimicrobial DPPH scavenging assay 1,3,5-Triaryl-2-pyrazoline Molecular docking metRS Molecular recognition 

Notes

Acknowledgments

The authors are thankful to Mangalore University and the UGC-SAP for financial assistance for the purchase of chemicals. MTHK is grateful to Prof. Ingebrigt Sylte, Medical Pharmacology and Toxicology, Department of Medical Biology, Faculty of Health Science, University of Tromsø, N-9037 Tromsø, Norway, for the access of the license of ICM-Pro version.

References

  1. Abagyan RA, Totrov MM, Kuznetsov DA (1994) ICM: a new method for protein modeling and design: applications to docking and structure prediction from the distorted native conformation. J Comp Chem 15:488–506CrossRefGoogle Scholar
  2. Amir M, Kumar S (2005) Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of 3,5-dimethyl pyrazoles, 3-methyl pyrazol-5-ones and 3,5-disubstituted pyrazolines. Indian J Chem 44B:2532–2537Google Scholar
  3. Amir M, Kumar H, Khan S (2008) A synthesis and pharmacological evaluation of pyrazoline derivatives as new anti-inflammatory and analgesic agents. Bioorg Med Chem Lett 18:918–922PubMedCrossRefGoogle Scholar
  4. Ankhiwala MD, Hathi MV (1996) Synthesis and antibacterial activity of some 1-phenyl-3,5-diaryl-2-P pyrazolines. Ind J Het Chem 5:229–230Google Scholar
  5. Azarifar D, Ghasemnejad H (2003) Microwave-assisted synthesis of some 3,5-arylated 2-pyrazolines. Molecules 8:642–648CrossRefGoogle Scholar
  6. Bagavant G, Gole SR, Joshi VW, Soni SB (1994) Studies on anti-inflammatory and analgesic activities of itaconic acid systems. Part 1: itaconoc acids and diesters. Ind J Pharm Sci 56:80–85Google Scholar
  7. Baktır Z, Akkurt M, Samshuddin S, Narayana B, Yathirajan HS (2011) 3,5-Bis(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazole. Acta Cryst E67:o328–o329Google Scholar
  8. Butcher RJ, Akkurt M, Samshuddin S, Narayana B, Yathirajan HS (2011) 3,5-Bis(4-methylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazole. Acta Cryst E 67:o1019CrossRefGoogle Scholar
  9. Fun HK, Hemamalini M, Samshuddin S, Narayana B, Yathirajan HS (2010) 1-[3,5-Bis(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone. Acta Cryst E 66:o582–o583CrossRefGoogle Scholar
  10. Fustero S, Fuentes AS, Sanz-Cervera JF (2009) Recent advances in the synthesis of pyrazoles—a review. Org Prep Proced Int 41:253–290CrossRefGoogle Scholar
  11. Grosscurt AC, Hes RV, Wellnga K (1979) 1-Phenylcarbamoyl-2-pyrazolines, a new class of insecticides. 3. Synthesis and insecticidal properties of 3,4-diphenyl-1-phenylcarbamoyl-2-pyrazolines. J Agric Food Chem 27:406–409CrossRefGoogle Scholar
  12. Halgren TA (1996a) Merck molecular force field. III. Molecular geometries and vibrational frequencies. J Comp Chem 17:553–586CrossRefGoogle Scholar
  13. Halgren TA (1996b) Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J Comp Chem 17:520–552CrossRefGoogle Scholar
  14. Halgren TA (1996c) Merck molecular force field. V. Extension of MMFF94 using experimental data, additional computational data and empirical rules. J Comp Chem 17:616–641CrossRefGoogle Scholar
  15. Halgren TA (1996d) Merck molecular force field: I. Basis, form, scope, parameterization and performance of MMFF94. J Comp Chem 17:490–519CrossRefGoogle Scholar
  16. Halgren TA (1999a) MMFF VI. MMFF94 s option for energy minimization studies. J Comp Chem 20:720–729CrossRefGoogle Scholar
  17. Halgren TA (1999b) MMFF VII. Characterization of MMFF94, MMFF94 s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries. J Comp Chem 20:730–748CrossRefGoogle Scholar
  18. Halgren TA, Nachbar RB (1996) Merck molecular force field. IV. Conformational energies and geometries for MMFF94. J Comp Chem 17:587–615Google Scholar
  19. Harish BG, Krishna V, Sharath R, Kumara S, Raja N, Mahadevan KM (2007) Antibacterial activity of celapanin, a sesquiterpene isolated from the leaves of Celastrus paniculatus Willd. Int J Biomed Pharm Sci 1:65–68Google Scholar
  20. Hes RV, Wellinga K, Grosscurt AC (1978) 1-Phenylcarbamoyl-2-pyrazolines: a new class of insecticides. 2. Synthesis and insecticidal properties of 3,5-diphenyl-1-phenylcarbamoyl-2-pyrazolines. J Agric Food Chem 26:915–918CrossRefGoogle Scholar
  21. Hurdle JG, O’Neill AJ, Chopra I (2005) Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents. Antimicrob Age Chemother 49:4821–4833CrossRefGoogle Scholar
  22. Jasinski JP, Guild CJ, Samshuddin S, Narayana B, Yathirajan HS (2010a) 3,5-Bis(4-fluorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole. Acta Cryst E 66:o1948–o1949CrossRefGoogle Scholar
  23. Jasinski JP, Pek AE, Samshuddin S, Narayana B, Yathirajan HS (2010b) 1-[3,5-Bis(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone. Acta Cryst E 66:o1950–o1951CrossRefGoogle Scholar
  24. Khan MT, Fuskevag OM, Sylte I (2009) Discovery of potent thermolysin inhibitors using structure based virtual screening and binding assays. J Med Chem 52:48–61PubMedCrossRefGoogle Scholar
  25. Klimova EI, Marcos M, Klimova TB, Cecilio AT, Ruben AT, Lena RR (1999) The structure of bicyclic ferrocenylmethylene substituted 2-pyrazolines and their reactions with azodicarboxylic acid N-phenylimide. J Organomet Chem 585:106–111CrossRefGoogle Scholar
  26. Knorr L (1893) Notiz über die pyrazolinreaction. Ber Dt Chem Ges 26:100–103CrossRefGoogle Scholar
  27. Kokura S, Yoshida N, Sakamoto N, Ishikawa T, Takagi T, Higashihara H, Nakabe N, Handa O, Naito Y, Yoshikawa T (2005) The radical scavenger edaravone. Cancer Lett 229:223–233PubMedCrossRefGoogle Scholar
  28. Lapan KA, Chapple JP, Galcheva-Gargova Z, Yang M, Tao J (2002) Peptide ligands in antibacterial drug discovery: use as inhibitors in target validation and target-based screening. Expert Opin Ther Targets 6:507–516PubMedCrossRefGoogle Scholar
  29. Nithitanakool S, Pithayanukul P, Bavovada R, Saparpakorn P (2009) Molecular docking studies and anti tyrosinase activity of Thai mango seed kernel extract. Molecules 14:257–265PubMedCrossRefGoogle Scholar
  30. Raghavendra R, Neelagund S (2009) Partial purification and biochemical characterization of antimicrobial and analgesic novel bioactive protein (substances) from Silkworm (Bombyx mori Linn.) fecal matter. Int J Bio med Pharm Sci 3:74–78Google Scholar
  31. Rajendra Prasad Y, Lakshmana Rao A, Prasoona L, Murali K, Ravi Kumar P (2005) Synthesis and antidepressant activity of some 1,3,5-triphenyl-2-pyrazolines and 3-(2′′-hydroxy naphthalen-1′′-yl)-1,5-diphenyl-2-pyrazolines. Bioorg Med Chem Lett 15:5030–5034PubMedCrossRefGoogle Scholar
  32. Safaei-Ghomi JH, Bamoniri A, Soltanian-Telkabadi M (2006) A modified and convenient method for the preparation of N-phenylpyrazoline derivatives. Chem Het Compd 42:892–896Google Scholar
  33. Samshuddin S, Narayana B, Yathirajan HS, Safwan AP, Tiekink ERT (2010) 3,5-Bis(4-bromophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole. Acta Cryst E 66:o1279–o1280CrossRefGoogle Scholar
  34. Sarojini BK, Vidyagayatri M, Darshanraj CG, Bharath BR, Manjunatha H (2010) DPPH scavenging assay of novel 1,3-disubstituted-1H-pyrazol-5-ols and their in silico studies on some proteins involved in Alzheimer’s disease signaling cascade. Lett Drug Des Disc 7:214–224CrossRefGoogle Scholar
  35. Satyanarayana K, Rao MNA (1993) Synthesis of 3-[4-[2,3-dihydro-2-(substituted aryl)-1,5-benzothiazepin-4-yl] phenyl] sydnones as potential antiinflammatory agents. Ind J Pharm Sci 55:230–233Google Scholar
  36. Saundane AR, Rudresh K, Satynarayana ND, Hiremath SP (1998) Pharmacological screening of 6H, 11H-indolo {3,2-C}isoquinolin-5-ones and their derivatives. Ind J Pharm Sci 60:379–383Google Scholar
  37. Schapira M, Totrov M, Abagyan R (1999) Prediction of the binding energy for small molecules, peptides and proteins. J Mol Recog 12:177–190CrossRefGoogle Scholar
  38. Sharath R, Krishna V, Sathyanarayana BN, Harish B (2008) Antibacterial activity of Bacoside-A–an active constituent isolated of Bacopa monnieri (L.) Wettest. Pharmacologyonline 2:517–528Google Scholar
  39. Sugiura I, Nureki O, Ugaji-Yoshikawa Y, Kuwabara S, Shimada A, Tateno M, Lorber B, Giege R, Moras D, Yokoyama S, Konno M (2000) The 2.0 A crystal structure of thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules. Structure 8:197–208PubMedGoogle Scholar
  40. Taylor RD, Jewsbury PJ, Essex JW (2002) A review of protein-small molecule docking methods. J Comput Aided Mol Des 16(3):151–166PubMedCrossRefGoogle Scholar
  41. Thakare VG, Wadodkar KN (1986) Synthesis of isomeric ∆2-pyrazolines. Ind J Chem 25B:610–613Google Scholar
  42. Tiwari AK (2004) Antioxidants: new-generation therapeutic base for treatment of polygenic disorders. Curr Sci 86:1092–1100Google Scholar
  43. Vagdevi HM, Latha KP, Vaidya VP, Vijaya kumar ML, Pai KSR (2001) Synthesis and pharmacological screening of some Novel Naphtho [2,1-b] furo-pyrazolines, isoxazoles and isoxazolines. Ind J Pharm Sci 63:286–291Google Scholar
  44. Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127–134PubMedCrossRefGoogle Scholar
  45. Wei DQ, Zhang R, Du QS, Gao WN, Li Y, Gao H, Wang SQ, Zhang X, Li AX, Sirois S, Chou KC (2006) Anti-SARS drug screening by molecular docking. Amino Acids 31:73–80PubMedCrossRefGoogle Scholar
  46. Wiley RH, Jarboe CH, Hayes FN, Hansbury E, Nielsen JT, Callahan PX, Sellars M (1958) 1,3,5-Triaryl-2-pyrazoline for use as scintillation solutes. J Org Chem 23:732–738CrossRefGoogle Scholar
  47. Zhang XH, Wu SK, Gao ZQ, Lee CS, Lee ST, Kwong HL (2000) Pyrazoline derivatives for blue color emitter in organic electroluminescent devices. Thin Solid Films 371:40–46CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Seranthimata Samshuddin
    • 1
  • Badiadka Narayana
    • 1
  • Balladka Kunhanna Sarojini
    • 2
  • Mahmud Tareq Hassan Khan
    • 3
  • Hemmige S. Yathirajan
    • 4
  • Chenna Govindaraju Darshan Raj
    • 2
  • Ramappa Raghavendra
    • 5
  1. 1.Department of Studies in ChemistryMangalore UniversityMangalagangotriIndia
  2. 2.Research Department of ChemistryP. A College of Engineering, NadupadavuMangaloreIndia
  3. 3.TromsøNorway
  4. 4.Department of Studies in ChemistryUniversity of MysoreMysoreIndia
  5. 5.Department of Postgraduate Studies and Research in BiochemistryJnana Sahyadri, Kuvempu UniversityShimogaIndia

Personalised recommendations