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Year 2021, Volume: 42 Issue: 4, 806 - 813, 29.12.2021

Derya Osmaniye , Begüm Nurpelin Saglik

Abstract

Piyasada mevcut COX inhibitörlerinin yan etki profillerinin çok fazla olması ve bu yan etkilerin çoğunun non-selektif inhibitörlerden kaynaklı olması yeni selektif COX-1 inhibitörlerine ihtiyacı arttırmaktadır.3 yeni bileşikten oluşan 2-(4-((4-(Sübstitüefenil)tiyazol-2-il)amino)fenil)asetik asit (3a-3c) serisi sentezlenmiştir. Elde edilen bileşiklerin yapıları, 1H-NMR, 13C-NMR ve kütle spektroskopisi gibi spektroskopik analiz yöntemleri ile aydınlatılmıştır. Bileşiklerin in vitro COX inhibitör aktivitesi florimetrik yöntemler kullanılarak yapılmıştır.Sentezlenen bileşikler içerisinde 3c kodlu bileşik COX-1 enzimine karşı referans ilaç ile benzer etkinlik göstermiştir.Sentezlenen bileşiklerin selektif COX-1 inhibitör potansiyelleri incelendiğinde 3c bileşiği ön plana çıkmaktadır. Bu çalışmanın sonuçlarına göre, projede aktif türev üzerinden yapılacak modifikasyonlar ile, sentezlenecek yeni bileşiklerin selektif COX-1 inhibitör aktivitelerinin araştırılması önerilmektedir.

Keywords

COX-1 Tiyazol Asetik asit

References

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  • [4] Perrone M.G., Lofrumento D.D., Vitale P., De Nuccio F., La Pesa V., Panella A., Calvello R., Cianciulli A., Panaro M.A., Scilimati A. Selective Cyclooxygenase-1 Inhibition by P6 and Gastrotoxicity: Preliminary Investigation, Pharmacology, 95(1-2) (2015) 22-28.
  • [5] Vitale P., Panella A., Scilimati A., Perrone M.G., COX‐1 Inhibitors: Beyond Structure Toward Therapy, Med. Chem. Rew., 36(4) (2016) 641-671.
  • [6] G Perrone M., Scilimati A., Simone L., Vitale P. Selective COX-1 inhibition: A therapeutic target to be reconsidered, Curr. Med. Chem., 17(32) (2010) 3769-3805.
  • [7] Mitchell J.A., Kirkby N.S., Eicosanoids, Prostacyclin and Cyclooxygenase in the Cardiovascular System, Br. J. Pharmacol., 176(8) (2019) 1038-1050.
  • [8] Perrone M.G., Miciaccia M., Vitale P., Ferorelli S., Araújo C.D.C.B., de Almeida G.S., Domingos T.F.S., Silva L.C.R.P., Padula M., Cabral L.M., Sathler P.C., Bonaccorso C., Fortuna C.G., Scilimati A. An Attempt to Chemically State the Cross-Talk Between Monomers of COX Homodimers by Double/Hybrid Inhibitors Mofezolac-Spacer-Mofezolac and Mofezolac-Spacer-Arachidonic Acid, Eur. J. Med. Chem., 209 (2021) 112919.
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  • [10] Sharma R.N., Xavier F.P., Vasu K.K., Chaturvedi S.C., Pancholi S.S., Synthesis of 4-Benzyl-1,3-Thiazole Derivatives as Potential Anti-Infammatory Agents: An Analogue-Based Drug Design Approach, J. Enzym. Inhibit. Med. Chem., 24 (2009) 890–897.
  • [11] Bell F.W., Cantrell A.S., Hoegberg M., Jasknas S.R., Johansson N.G., Jordan C.L., Kinnick M.D., Lind P., Morin J.M., Noreen R., Öberg B., Palkowitz J.A., Parrish C.A., Pranc P., Sahlberg C., Ternansky R.J., Vasileff R.T., Vrang L., West S.J., Zhang H., Morin Jr J.M., Phenethylthiazolethiourea (PETT) Compounds, A New Class of HIV-1 Reverse Transcriptase Inhibitors. 1. Synthesis and Basic Structure-Activity Relationship Studies of PETT Analogs, J. Med. Chem., 38(25) (1995) 4929-4936.
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  • [17] Rudolph J., Theis H., Hanke R., Endermann R., Johannsen L., Geschke F.U., Seco-Cyclothialidines: New Concise Synthesis, Inhibitory Activity Toward Bacterial and Human DNA Topoisomerases, and Antibacterial Properties, J. Med. Chem., 44(4) (2001) 619-626.
  • [18] Badorc A., Bordes M.F., de Cointet P., Savi P., Bernat A., Lalé A., Petitou M., Maffrand J.P., Herbert J.M., New Orally Active Non-Peptide Fibrinogen Receptor (Gpiib-Iiia) Antagonists: Identification of Ethyl 3-[N-[4-[4-[amino [(ethoxycarbonyl)imino]methyl]phenyl]-1,3-thiazol-2-yl]-N-[1-[(ethoxycarbonyl)methyl] piperidin-4-yl]amino]propionate (SR 121787) as a Potent and Long-Acting Antithrombotic Agent, J. Med. Chem., 40(21) (1997) 3393-3401.
  • [19] Khidre R.E., Radini I.A.M., Design, Synthesis and Docking Studies of Novel Thiazole Derivatives Incorporating Pyridine Moiety and Assessment as Antimicrobial Agents, Scientific Reports, 11(1) (2021) 1-10.
  • [20] Biovision COX-1 Fluorescent Inhibitor Screening Kit (Catalog No: K548-100) manual, http://www.biovision.com/manuals/K548.pdf.
  • [21] Biovision COX-2 Fluorescent Inhibitor Screening Kit (Catalog No: K547-100) manual, http://www.biovision.com/manuals/K547.pdf.
  • [22] Kaya Çavuşoğlu B., Sağlık B.N., Acar Çevik U., Osmaniye D., Levent S., Özkay Y., Kaplancıklı Z. A., Design, Synthesis, Biological Evaluation, and Docking Studies of Some Novel Chalcones as Selective COX‐2 Inhibitors, Arch. Pharm., 354(3) (2021) 2000273.
  • [23] Sağlık B.N., Osmaniye D., Levent S., Acar Çevik U., Çavuşoğlu Kaya B., Özkay Y., Kaplancıklı Z. A., Design, Synthesis and Biological Assessment of New Selective COX-2 Inhibitors Including Methyl Sulfonyl Moiety, Eur. J. Med. Chem., 209 (2021) 112918.
  • [24] Selinsky B.S., Gupta K., Sharkey C.T., Loll P.J., Structural Analysis of NSAID Binding by Prostaglandin H2 Synthase: Time-Dependent and Time-Independent Inhibitors Elicit Identical Enzyme Conformations, Biochemistry, 40(17) (2001) 5172-5180.
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Synthesis, characterization and biological activity evaluation of novel thiazole derivatives containing acetic acid residue as selective COX-1 inhibitors

Year 2021, Volume: 42 Issue: 4, 806 - 813, 29.12.2021

Derya Osmaniye , Begüm Nurpelin Saglik

Abstract

The fact that the side effect profiles of the COX inhibitors available in the market is very high and most of these side effects are caused by non-selective inhibitors increases the need for new selective COX-1 inhibitors. In this study, carried out to develop a new COX-1 inhibitor, the thiazole ring system was preferred because of its known activity in the vary different field. Additionally, The acid residue, which is in the structure of the most commonly used COX inhibitors such as ıbuprofen and flurbiprofen, was synthesized. 2-(4-((4-(Substituted phenyl)thiazol-2-yl)amino)phenyl)acetic acid (3a-3c) series consisting of 3 new compounds was synthesized. The structures of the obtained compounds were elucidated using 1H-NMR, 13C-NMR and mass spectroscopy data. The in vitro COX inhibitory activity of the compounds was determined using fluorimetric methods.Among the synthesized compounds, the compound 3c showed similar activity with the reference drug against the COX-1 enzyme. When the selective COX-1 inhibitory potentials of the synthesized compounds are examined, compound 3c comes to the fore. According to the results of this study, it is recommended to investigate the selective COX-1 inhibitory activities of new compounds to be synthesized with modifications to be made on the active derivative in the project.

Keywords

COX-1 Thiazole Acetic acide

References

  • [1]Abdellatif K.R., Abdelall E.K., Fadaly W.A., Kamel G. M., Synthesis, Cyclooxygenase Inhibition, and Anti-Inflammatory Evaluation of Novel Diarylheterocycles with a Central Pyrazole, Pyrazoline, or Pyridine Ring, Med. Chem. Res., 24(6) (2015) 2632-2644.
  • [2] Abdellatif K.R., Abdelgawad M.A., Elshemy H.A., Alsayed S.S., Kamel, G., Synthesis and Anti-Inflammatory Evaluation of New 1, 3, 5-Triaryl-4, 5-Dihydro-1H-Pyrazole Derivatives Possessing an Aminosulphonyl Pharmacophore, Arch. Pharm. Res., 38(11) (2015) 1932-1942.
  • [3] Kankala S., Kankala R.K., Gundepaka P., Thota N., Nerella S., Gangula M.R., Guguloth H., Kagga M., Vadde R., Vasam C.S., Regioselective Synthesis of Isoxazole–Mercaptobenzimidazole Hybrids and Their In Vivo Analgesic and Anti-Inflammatory Activity Studies, Bioorg. Med. Chem. Lett., 23(5) (2013) 1306-1309.
  • [4] Perrone M.G., Lofrumento D.D., Vitale P., De Nuccio F., La Pesa V., Panella A., Calvello R., Cianciulli A., Panaro M.A., Scilimati A. Selective Cyclooxygenase-1 Inhibition by P6 and Gastrotoxicity: Preliminary Investigation, Pharmacology, 95(1-2) (2015) 22-28.
  • [5] Vitale P., Panella A., Scilimati A., Perrone M.G., COX‐1 Inhibitors: Beyond Structure Toward Therapy, Med. Chem. Rew., 36(4) (2016) 641-671.
  • [6] G Perrone M., Scilimati A., Simone L., Vitale P. Selective COX-1 inhibition: A therapeutic target to be reconsidered, Curr. Med. Chem., 17(32) (2010) 3769-3805.
  • [7] Mitchell J.A., Kirkby N.S., Eicosanoids, Prostacyclin and Cyclooxygenase in the Cardiovascular System, Br. J. Pharmacol., 176(8) (2019) 1038-1050.
  • [8] Perrone M.G., Miciaccia M., Vitale P., Ferorelli S., Araújo C.D.C.B., de Almeida G.S., Domingos T.F.S., Silva L.C.R.P., Padula M., Cabral L.M., Sathler P.C., Bonaccorso C., Fortuna C.G., Scilimati A. An Attempt to Chemically State the Cross-Talk Between Monomers of COX Homodimers by Double/Hybrid Inhibitors Mofezolac-Spacer-Mofezolac and Mofezolac-Spacer-Arachidonic Acid, Eur. J. Med. Chem., 209 (2021) 112919.
  • [9] Haragave K.D., Hess F.K. Oliver J.T., N-(4-Substituted-Thiazolyl) Oxamic Acid Derivatives, New Series of Potent, Orally Active Antiallergy Agents, J. Med. Chem., 26(8) (1998) 1158–1163.
  • [10] Sharma R.N., Xavier F.P., Vasu K.K., Chaturvedi S.C., Pancholi S.S., Synthesis of 4-Benzyl-1,3-Thiazole Derivatives as Potential Anti-Infammatory Agents: An Analogue-Based Drug Design Approach, J. Enzym. Inhibit. Med. Chem., 24 (2009) 890–897.
  • [11] Bell F.W., Cantrell A.S., Hoegberg M., Jasknas S.R., Johansson N.G., Jordan C.L., Kinnick M.D., Lind P., Morin J.M., Noreen R., Öberg B., Palkowitz J.A., Parrish C.A., Pranc P., Sahlberg C., Ternansky R.J., Vasileff R.T., Vrang L., West S.J., Zhang H., Morin Jr J.M., Phenethylthiazolethiourea (PETT) Compounds, A New Class of HIV-1 Reverse Transcriptase Inhibitors. 1. Synthesis and Basic Structure-Activity Relationship Studies of PETT Analogs, J. Med. Chem., 38(25) (1995) 4929-4936.
  • [12] Patt W.C., Hamilton H.W., Taylor M.D., Ryan M.J., Taylor Jr D.G., Connolly C.J., Doherty A.M., Clutchko S.R., Sircar I.., Steinbaugh B.A., Batley B.L., Painchaud C.A., Rapundalo S.T., Michniewicz B.M., Sircar I., Structure-Activity Relationships of a Series of 2-Amino-4-Thiazole-Containing Renin Inhibitors, J. Med. Chem., 35(14) (1992) 2562-2572.
  • [13] Tsuji K., Ishikawa H., Synthesis and Anti-Pseudomonal Activity of New 2-Isocephems with a Dihydroxypyridone Moiety at C-7, Bioorg. Med. Chem. Lett., 4(13) (1994) 1601-1606.
  • [14] Ergenç N., Çapan G., Günay N.S., Özkirimli S., Güngör M., Özbey S., Kendi E. Synthesis and Hypnotic Activity of New 4‐Thiazolidinone and 2‐Thioxo‐4, 5‐Imidazolidinedione Derivatives, Arch. Pharm., 332(10) (1999) 343-347.
  • [15] Jaen J.C., Wise L.D., Caprathe B.W., Tecle H., Bergmeier S., Humblet C.C., Heffner T.G., Meltzer L.T., Pugsley T.A. 4-(1, 2, 5, 6-Tetrahydro-1-Alkyl-3-Pyridinyl)-2-Thiazolamines: A Novel Class of Compounds with Central Dopamine Agonist Properties, J. Med. Chem., 33(1) (1990) 311-317.
  • [16] Carter J.S., Kramer S., Talley J.J., Penning T., Collins P., Graneto M.J., Seibert K., Koboldt C.M., Masferrer K.J., Zweifel B., Synthesis and Activity of Sulfonamide-Substituted 4,5-Diaryl Thiazoles as Selective Cyclooxygenase-2 Inhibitors, Bioorg. Med. Chem. Lett., 9(8) (1999) 1171-1174.
  • [17] Rudolph J., Theis H., Hanke R., Endermann R., Johannsen L., Geschke F.U., Seco-Cyclothialidines: New Concise Synthesis, Inhibitory Activity Toward Bacterial and Human DNA Topoisomerases, and Antibacterial Properties, J. Med. Chem., 44(4) (2001) 619-626.
  • [18] Badorc A., Bordes M.F., de Cointet P., Savi P., Bernat A., Lalé A., Petitou M., Maffrand J.P., Herbert J.M., New Orally Active Non-Peptide Fibrinogen Receptor (Gpiib-Iiia) Antagonists: Identification of Ethyl 3-[N-[4-[4-[amino [(ethoxycarbonyl)imino]methyl]phenyl]-1,3-thiazol-2-yl]-N-[1-[(ethoxycarbonyl)methyl] piperidin-4-yl]amino]propionate (SR 121787) as a Potent and Long-Acting Antithrombotic Agent, J. Med. Chem., 40(21) (1997) 3393-3401.
  • [19] Khidre R.E., Radini I.A.M., Design, Synthesis and Docking Studies of Novel Thiazole Derivatives Incorporating Pyridine Moiety and Assessment as Antimicrobial Agents, Scientific Reports, 11(1) (2021) 1-10.
  • [20] Biovision COX-1 Fluorescent Inhibitor Screening Kit (Catalog No: K548-100) manual, http://www.biovision.com/manuals/K548.pdf.
  • [21] Biovision COX-2 Fluorescent Inhibitor Screening Kit (Catalog No: K547-100) manual, http://www.biovision.com/manuals/K547.pdf.
  • [22] Kaya Çavuşoğlu B., Sağlık B.N., Acar Çevik U., Osmaniye D., Levent S., Özkay Y., Kaplancıklı Z. A., Design, Synthesis, Biological Evaluation, and Docking Studies of Some Novel Chalcones as Selective COX‐2 Inhibitors, Arch. Pharm., 354(3) (2021) 2000273.
  • [23] Sağlık B.N., Osmaniye D., Levent S., Acar Çevik U., Çavuşoğlu Kaya B., Özkay Y., Kaplancıklı Z. A., Design, Synthesis and Biological Assessment of New Selective COX-2 Inhibitors Including Methyl Sulfonyl Moiety, Eur. J. Med. Chem., 209 (2021) 112918.
  • [24] Selinsky B.S., Gupta K., Sharkey C.T., Loll P.J., Structural Analysis of NSAID Binding by Prostaglandin H2 Synthase: Time-Dependent and Time-Independent Inhibitors Elicit Identical Enzyme Conformations, Biochemistry, 40(17) (2001) 5172-5180.
  • [25] RCSB, Protein Data Bank. Biological Macromolecular Structures Enabling Breakthroughs in Research and Education, Available at: rcsb.org/structure/1EQH. Retrieved June 2, 2021
  • [26] Maestro, Maestro, version 10.6, Schrödinger, LLC, New York, NY, (2016).
  • [27] Schrödinger, LLC, New York, NY, (2016).
  • [28] LigPrep, Schrödinger, LLC, New York, NY, (2016).
  • [29] Glide, Schrödinger, LLC, New York, NY, (2016).
There are 29 citations in total.

Details

Primary Language English
Subjects Structural Biology, Pharmacology and Pharmaceutical Sciences, Nonlinear Optics and Spectroscopy
Journal Section Natural Sciences
Authors

Derya Osmaniye 0000-0002-0499-436X

Begüm Nurpelin Saglik 0000-0002-0151-6266

Publication Date December 29, 2021
Submission Date July 9, 2021
Acceptance Date November 2, 2021
Published in Issue Year 2021Volume: 42 Issue: 4

Cite

APA Osmaniye, D., & Saglik, B. N. (2021). Synthesis, characterization and biological activity evaluation of novel thiazole derivatives containing acetic acid residue as selective COX-1 inhibitors. Cumhuriyet Science Journal, 42(4), 806-813.