Research Articles

Pyrazoline carboxylates as selective MAO-B inhibitors: Synthesis and Biological screening

Vol. 2 No. 1 (2015) 1-5 Published June 20, 2015

1,253 Views312 Downloads7 Citations

PDF

Abstract

A series of carboxylates of pyrazolines (3a-3h) were synthesized from ethyl 2-benzylidene-3-oxobutanoate esters using hydrazine hydrate and ethanol as solvent. All the compounds (3a-3h) screened for their MAO inhibitory activity using rat brain MAO. All the compounds were found to be selective, reversible and competitive inhibitors of MAO-B except compound 3d and 3h which was found to be non-selective. These compounds were found to be active against MAO-B at concentration close to 1 ?M (3e = 0.99 ?M, 3a = 0.92 ?M and 3b = 1.11?M). Compound 3a was potent amongst these while 3b was more selective towards MAO-B with selectivity index 2.88.

References

  1. Tipton, K. F.; Boyce, S.; O'Sullivan, J.; Davey, G. P.; Healy, J., Monoamine oxidases: certainties and uncertainties. Curr Med Chem 2004, 11, 1965-1982.
  2. http://dx.doi.org/10.2174/0929867043364810 DOI: https://doi.org/10.2174/0929867043364810
  3. Slotkin, T. A., Mary Bernheim and the discovery of monoamine oxidase. Brain Res bull 1999, 50, 373.
  4. http://dx.doi.org/10.1016/S0361-9230(99)00110-0 DOI: https://doi.org/10.1016/S0361-9230(99)00110-0
  5. Hare, M. L. C., Tyramine oxidase: A new enzyme system in liver. Biochem J 1928, 22, 968. DOI: https://doi.org/10.1042/bj0220968
  6. Bach, A.; Lan, N. C.; Johnson, D. L.; Abell, C. W.; Bembenek, M. E.; Kwan, S.-W.; Seeburg, P. H.; Shih, J. C., cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci 1988, 85, 4934-4938.
  7. http://dx.doi.org/10.1073/pnas.85.13.4934 DOI: https://doi.org/10.1073/pnas.85.13.4934
  8. Collins, G.; Sandler, M.; Williams, E.; Youdim, M., Multiple forms of human brain mitochondrial monoamine oxidase. Nature 1970, 225, 817-820.
  9. http://dx.doi.org/10.1038/225817a0 DOI: https://doi.org/10.1038/225817a0
  10. Youdim, M.; Collins, G.; Sandler, M.; Jones, A. B.; Pare, C.; Nicholson, W., Biological Sciences: Human brain monoamine oxidase: Multiple forms and selective inhibitors. Nature 1972, 236, 225-228.
  11. http://dx.doi.org/10.1038/236225b0 DOI: https://doi.org/10.1038/236225b0
  12. Johnston, J., Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 1968, 17, 1285-1297.
  13. http://dx.doi.org/10.1016/0006-2952(68)90066-X DOI: https://doi.org/10.1016/0006-2952(68)90066-X
  14. Knoll, J.; Magyar, K., Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharmacol 1971, 5, 393-408.
  15. Kalgutkar, A. S.; Castagnoli, N.; Testa, B., Selective inhibitors of monoamine oxidase (MAO?A and MAO?B) as probes of its catalytic site and mechanism. Med Res Rev 1995, 15, 325-388.
  16. http://dx.doi.org/10.1002/med.2610150406 DOI: https://doi.org/10.1002/med.2610150406
  17. Pacher, P.; Kohegyi, E.; Kecskemeti, V.; Furst, S., Current trends in the development of new antidepressants. Curr Med Chem 2001, 8, 89-100.
  18. http://dx.doi.org/10.2174/0929867013373796 DOI: https://doi.org/10.2174/0929867013373796
  19. Pacher, P.; Kecskemeti, V., Trends in the development of new antidepressants. Is there a light at the end of the tunnel? Curr Med Chem 2004, 11, 925.
  20. http://dx.doi.org/10.2174/0929867043455594 DOI: https://doi.org/10.2174/0929867043455594
  21. Carreiras, M.; Marco, J., Recent approaches to novel anti-Alzheimer therapy. Curr Pharm Design 2004, 10, 3167-3176.
  22. http://dx.doi.org/10.2174/1381612043383421 DOI: https://doi.org/10.2174/1381612043383421
  23. Chimenti, F.; Bolasco, A.; Manna, F.; Secci, D.; Chimenti, P.; Befani, O.; Turini, P.; Giovannini, V.; Mondov, B.; Cirilli, R., Synthesis and selective inhibitory activity of 1-acetyl-3, 5-diphenyl-4, 5-dihydro-(1 H)-pyrazole derivatives against monoamine oxidase. J Med Chem 2004, 47, 2071-2074.
  24. http://dx.doi.org/10.1021/jm031042b DOI: https://doi.org/10.1021/jm031042b
  25. Chimenti, F.; Maccioni, E.; Secci, D.; Bolasco, A.; Chimenti, P.; Granese, A.; Befani, O.; Turini, P.; Alcaro, S.; Ortuso, F., Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of 1-thiocarbamoyl-3, 5-diaryl-4, 5-dihydro-(1 H)-pyrazole derivatives. J Med Chem 2005, 48, 7113-7122.
  26. http://dx.doi.org/10.1021/jm040903t DOI: https://doi.org/10.1021/jm040903t
  27. Secci, D.; Bolasco, A.; Chimenti, P.; Carradori, S., The state of the art of pyrazole derivatives as monoamine oxidase inhibitors and antidepressant/anticonvulsant agents. Curr Med Chem 2011, 18, 5114-5144.
  28. http://dx.doi.org/10.2174/092986711797636090 DOI: https://doi.org/10.2174/092986711797636090
  29. Khalil, N. A.; Ahmed, E. M.; El-Nassan, H. B.; Ahmed, O. K.; Al-Abd, A. M., Synthesis and biological evaluation of novel pyrazoline derivatives as anti-inflammatory and antioxidant agents. Arch Pharm Res 2012, 35, 995-1002.
  30. http://dx.doi.org/10.1007/s12272-012-0606-9 DOI: https://doi.org/10.1007/s12272-012-0606-9
  31. Azarifar, D.; Shaebanzadeh, M., Synthesis and characterization of new 3, 5-dinaphthyl substituted 2-pyrazolines and study of their antimicrobial activity. Molecules 2002, 7, 885-895.
  32. http://dx.doi.org/10.3390/71200885 DOI: https://doi.org/10.3390/71200885
  33. Ali, M. A.; Yar, M. S.; Kumar, M.; Pandian, G. S., Synthesis and antitubercular activity of substituted novel pyrazoline derivatives. Nat Prod Res 2007, 21, 575-579.
  34. http://dx.doi.org/10.1080/14786410701369367 DOI: https://doi.org/10.1080/14786410701369367
  35. Puig-Basagoiti, F.; Tilgner, M.; Forshey, B. M.; Philpott, S. M.; Espina, N. G.; Wentworth, D. E.; Goebel, S. J.; Masters, P. S.; Falgout, B.; Ren, P., Triaryl pyrazoline compound inhibits flavivirus RNA replication. Antimicrob Agents Chemother 2006, 50, 1320-1329.
  36. http://dx.doi.org/10.1128/AAC.50.4.1320-1329.2006 DOI: https://doi.org/10.1128/AAC.50.4.1320-1329.2006
  37. Kawazura, H.; Takahashi, Y.; Shiga, Y.; Shimada, F.; Ohto, N.; Tamura, A., Cerebroprotective effects of a novel pyrazoline derivative, MS-153, on focal ischemia in rats. Jpn J Pharmacol 1997, 73, 317-324. DOI: https://doi.org/10.1254/jjp.60.317
  38. http://dx.doi.org/10.1254/jjp.73.317 DOI: https://doi.org/10.1254/jjp.73.317
  39. Amir, M.; Kumar, H.; Khan, S. A., Synthesis and pharmacological evaluation of pyrazoline derivatives as new anti-inflammatory and analgesic agents. Bioorg Med Chem Lett 2008, 18, 918-922.
  40. http://dx.doi.org/10.1016/j.bmcl.2007.12.043 DOI: https://doi.org/10.1016/j.bmcl.2007.12.043
  41. Havrylyuk, D.; Zimenkovsky, B.; Vasylenko, O.; Zaprutko, L.; Gzella, A.; Lesyk, R., Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity. Eur J Med Chem 2009, 44, 1396-1404.
  42. http://dx.doi.org/10.1016/j.ejmech.2008.09.032 DOI: https://doi.org/10.1016/j.ejmech.2008.09.032
  43. Stirrett, K. L.; Ferreras, J. A.; Jayaprakash, V.; Sinha, B. N.; Ren, T.; Quadri, L. E., Small molecules with structural similarities to siderophores as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis. Bioorg Med Chem Lett 2008, 18, 2662-2668.
  44. http://dx.doi.org/10.1016/j.bmcl.2008.03.025 DOI: https://doi.org/10.1016/j.bmcl.2008.03.025
  45. zdemir, Z.; Kandilci, H. B.; Gm?el, B.; al??, .; Bilgin, A. A., Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)-pyrazoline derivatives. Eur J Med Chem 2007, 42, 373-379.
  46. http://dx.doi.org/10.1016/j.ejmech.2006.09.006 DOI: https://doi.org/10.1016/j.ejmech.2006.09.006
  47. Marella, A.; Ali, R.; Alam, T.; Saha, R.; Tanwar, O.; Akhter, M.; Shaquiquzzaman, M.; Mumtaz Alam, M., Pyrazolines: a biological review. Mini Rev Med Chem 2013, 13, 921-931.
  48. http://dx.doi.org/10.2174/1389557511313060012 DOI: https://doi.org/10.2174/1389557511313060012
  49. Jayaprakash, V.; Sinha, B. N.; Ucar, G.; Ercan, A., Pyrazoline-based mycobactin analogues as MAO-inhibitors. Bioorg Med Chem Lett 2008, 18, 6362-6368.
  50. http://dx.doi.org/10.1016/j.bmcl.2008.10.084 DOI: https://doi.org/10.1016/j.bmcl.2008.10.084
  51. Karuppasamy, M.; Mahapatra, M.; Yabanoglu, S.; Ucar, G.; Sinha, B. N.; Basu, A.; Mishra, N.; Sharon, A.; Kulandaivelu, U.; Jayaprakash, V., Development of selective and reversible pyrazoline based MAO-A inhibitors: Synthesis, biological evaluation and docking studies. Bioorg Med Chem 2010, 18, 1875-1881.
  52. http://dx.doi.org/10.1016/j.bmc.2010.01.043 DOI: https://doi.org/10.1016/j.bmc.2010.01.043
  53. Sahoo, A.; Yabanoglu, S.; Sinha, B. N.; Ucar, G.; Basu, A.; Jayaprakash, V., Towards development of selective and reversible pyrazoline based MAO-inhibitors: Synthesis, biological evaluation and docking studies. Bioorg Med Chem Lett 2010, 20, 132-136.
  54. http://dx.doi.org/10.1016/j.bmcl.2009.11.015 DOI: https://doi.org/10.1016/j.bmcl.2009.11.015
  55. Mishra, N.; Sasmal, D., Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation. Bioorg Med Chem Lett 2011, 21, 1969-1973.
  56. http://dx.doi.org/10.1016/j.bmcl.2011.02.030 DOI: https://doi.org/10.1016/j.bmcl.2011.02.030
  57. Vishnu Nayak, B.; Ciftci-Yabanoglu, S.; Jadav, S. S.; Jagrat, M.; Sinha, B. N.; Ucar, G.; Jayaprakash, V., Monoamine oxidase inhibitory activity of 3, 5-biaryl-4, 5-dihydro-1H-pyrazole-1-carboxylate derivatives. Eur J of Med Chem 2013, 69, 762-767.
  58. http://dx.doi.org/10.1016/j.ejmech.2013.09.010 DOI: https://doi.org/10.1016/j.ejmech.2013.09.010
  59. Sicker, D.; Rabe, A.; Zakrzewski, A.; Mann, G., Synthesis Of Substituted N-Hydroxylactams, Lactams, Quinoline-N-Oxides, And Quinolines By Catalyzed Reductive Cyclization Of 2-Nitrocinnamoyl Derivatives With Hydrogen Platinum Black. J Prak Chem 1987, 329, 1063-1070. DOI: https://doi.org/10.1002/chin.198830207
  60. http://dx.doi.org/10.1002/prac.19873290617 DOI: https://doi.org/10.1002/prac.19873290617
  61. Matharu, B.; Sharma, J.; Manrao, M., Synthesis and antifungal potential of 2-chlorobenzal derivatives. Pestic Res J 2006, 18, 113-115.
  62. Elkasaby, M., Michael Condensation Of Ethyl Alpha-Acetylcinnamates With Diethyl Malonate, Deoxybenzoin, Ethyl Phenylacetate, Benzyl Cyanide And Malononitrile. Indian J Chem 1976, B14, 739-741. DOI: https://doi.org/10.1002/chin.197718098
  63. Zuo, B.; Wang, Q.; Wang, Y.; Ma, Y., Knoevenagel condensation over acidic zeolite. Chinese J Catal 2002, 23, 555-558.
  64. Poindexter, G. S. 1,4-Dihydropyridine-3,5-dicarboxylates incorporating an alkyleneaminoalkylene-heteroatom moiety, procedure for their preparation, pharmaceutical compositions containing them, and their use as cardiovascular agents. EP247345A2, 1987.
  65. Holt, A.; Sharman, D. F.; Baker, G. B.; Palcic, M. M., A continuous spectrophotometric assay for monoamine oxidase and related enzymes in tissue homogenates. Anal Biochem 1997, 244, 384-392.
  66. http://dx.doi.org/10.1006/abio.1996.9911 DOI: https://doi.org/10.1006/abio.1996.9911
  67. Stanchev, S.; Momekov, G.; Jensen, F.; Manolov, I., Synthesis, computational study and cytotoxic activity of new 4-hydroxycoumarin derivatives. Eur J Med Chem 2008, 43, 694-706.
  68. http://dx.doi.org/10.1016/j.ejmech.2007.05.005 DOI: https://doi.org/10.1016/j.ejmech.2007.05.005
  69. El-Kasaby, M. A.; Salim, M. A. I., Some reactions with ethyl ?-acetylcinnamates. Egypt J Chem 1981, 23, 323-36.
  70. De Colibus, L.; Li, M.; Binda, C.; Lustig, A.; Edmondson, D. E.; Mattevi, A., Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B. Proc Natl Acad Sci 2005, 102, 12684-12689.
  71. http://dx.doi.org/10.1073/pnas.0505975102 DOI: https://doi.org/10.1073/pnas.0505975102

Author information

  • Vishnu Nayak Badavath

    Birla Institute of Technology

  • Alok Kumar Singh

    Birla Institute of Technology

  • Surender Singh Jadav

    Birla Institute of Technology, Mesra image/svg+xml

  • Nibha Mishra

    Birla Institute of Technology, Mesra image/svg+xml

  • Abhimanyu Dev

    Birla Institute of Technology, Mesra image/svg+xml

  • Barij Nayan Sinha

    Birla Institute of Technology, Mesra image/svg+xml

  • Venkatesan Jayaprakash

    Birla Institute of Technology

Rights and permissions

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

About this article

Cite this article

(1)
Badavath, V. N.; Singh, A. K.; Jadav, S. S.; Mishra, N.; Dev, A.; Sinha, B. N.; Jayaprakash, V. Pyrazoline Carboxylates As Selective MAO-B Inhibitors: Synthesis and Biological Screening. J Pharm Chem 2015, 2 (1), 1-5. https://doi.org/10.14805/jphchem.2015.art35.
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver

Download Citation

Endnote/Zotero/Mendeley (RIS) BibTeX
Received
January 29, 2015
Published
June 20, 2015
Section
Research Articles
Pages
1-5

Keywords

  • Pyrazoline
  • Rat liver enzyme
  • MAO isoform
  • Selectivity
  • Inhibitors

Most read articles by the same author(s)

1 2 > >>