CYCLOOXYGENASE-2 AS „IN SILICO“ TARGET OF PHENOLIC HYDRAZONE- TYPE DERIVATIVES

1st International Conference on Chemo and BioInformatics, ICCBIKG  2021, (324-327)

AUTHOR(S) / АУТОР(И): Jovica Branković, Vesna M. Milovanović, Vladimir P. Petrović

E-ADRESS / Е-АДРЕСА: jovica.brankovic@pmf.kg.ac.rs, vesna.milovanovic@pmf.kg.ac.rs, vladimir.petrovic@pmf.kg.ac.rs

Download Full Pdf   

DOI: 10.46793/ICCBI21.324B

ABSTRACT / САЖЕТАК:

In the present work, a series of phenolic hydrazone analogs were investigated in silico for their potential inhibitory activity toward COX-2. These examinations were based on the capability of hydrazone-based compounds to interact with numerous enzymes, as well as on their versatile biological features and therapeutical applications. COX-2 was selected due to its involvement in the inflammation and carcinogenesis processes. Regarding this, COX-2 represents a valid target for the development of compounds that could block the formation of harmful inflammation mediators.

KEY WORDS / КЉУЧНЕ РЕЧИ:

hydrazones, molecular docking, COX-2

REFERENCES / ЛИТЕРАТУРА:

  • Verma, A. Marella, M. Shaquiquzzaman, M. Akhtar, M.R. Ali, M.M. Alam, A review exploring biological activities of hydrazones, Journal of Pharmacy and Bioallied Sciences, 6 (2014) 69–80.
  • Baldisserotto, M. Demurtas, I. Lampronti, D. Moi, G. Balboni, S. Vertuani, S. Manfredini, Onnis, Benzofuran hydrazones as potential scaffold in the development of multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity, European Journal of Medicinal Chemistry, 156 (2018) 118–125.
  • Vasantha, G. Basavarajaswamy, M. Vaishali Rai, P. Boja, V.R. Pai, N. Shruthi, M. Bhat, Rapid “one-pot” synthesis of a novel benzimidazole-5-carboxylate and its hydrazone derivatives as potential anti-inflammatory and antimicrobial agents, Bioorganic & Medicinal Chemistry Letters, 25 (2015) 1420–1426
  • Nasr, S. Bondock, M. Youns, Anticancer activity of new coumarin substituted hydrazide- hydrazone derivatives, European Journal of Medicinal Chemistry, 76 (2014) 539–548
  • M.A. Abdelrahman, I. Salama, M.S. Gomaa, M.M. Elaasser, M.M. Abdel-Aziz, D.H. Soliman, Design, synthesis and 2D QSAR study of novel pyridine and quinolone hydrazone derivatives as potential antimicrobial and antitubercular agents, European Journal of Medicinal Chemistry, 138 (2017) 698–714.
  • Wahbeh, S. Milkowski, The Use of Hydrazones for Biomedical Applications, SLAS Technology, 24 (2019) 161–168.
  • C. Vanucci-Bacqué, C. Carayon, C. Bernis, C. Camare, A. Nègre-Salvayre, F. Bedos-Belval, M. Baltas, Synthesis, antioxidant and cytoprotective evaluation of potential antiatherogenic phenolic hydrazones. A structure-activity relationship insight, Bioorganic & Medicinal Chemistry, 22 (2014) 4269–4276.
  • S. Rollas, Ş.G. Küçükgüzel, Biological activities of hydrazone derivatives, Molecules. 12 (2007) 1910–1939.
  • J. de Oliveira Carneiro Brum, T.C.C. França, S.R. LaPlante, J.D.F. Villar, Synthesis and Biological Activity of Hydrazones and Derivatives: A Review, Mini-Reviews in Medicinal Chemistry, 20 (2019) 342–368.
  • S. Imran, M. Taha, N.H. Ismail, S.M. Kashif, F. Rahim, W. Jamil, M. Hariono, M. Yusuf, H. Wahab, Synthesis of novel flavone hydrazones: In-vitro evaluation of α-glucosidase inhibition, QSAR analysis and docking studies, European Journal of Medicinal Chemistry, 105 (2015) 156– 170.
  • M. Taha, N.H. Ismail, M.S. Baharudin, S. Lalani, S. Mehboob, K.M. Khan, S. Yousuf, S. Siddiqui, F. Rahim, M.I. Choudhary, Synthesis crystal structure of 2-methoxybenzoylhydrazones and evaluation of their α-glucosidase and urease inhibition potential, Medicinal Chemistry Research, 24 (2015) 1310–1324.
  • A.M. Cuadro, J. Valenciano, J.J. Vaquero, J. Alvarez-Builla, C. Sunkel, M.F. De Casa-Juana,
  • M.P. Ortega, Synthesis and biological evaluation of 2,6-di-tert-butylphenol hydrazones as 5- lipoxygenase inhibitors, Bioorganic & Medicinal Chemistry, 6 (1998) 173–180.
  • N. Mayer, M. Schweiger, M.C. Melcher, C. Fledelius, R. Zechner, R. Zimmermann, R. Breinbauer, Structure-activity studies in the development of a hydrazone based inhibitor of adipose-triglyceride lipase (ATGL), Bioorganic & Medicinal Chemistry, 23 (2015) 2904–2916.
  • A.R. Germain, L.C. Carmody, B. Morgan, C. Fernandez, E. Forbeck, T.A. Lewis, P.P. Nag, A. Ting, L. Verplank, Y. Feng, J.R. Perez, S. Dandapani, M. Palmer, E.S. Lander, P.B. Gupta, S.L. Schreiber, B. Munoz, Identification of a selective small molecule inhibitor of breast cancer stem cells, Bioorganic & Medicinal Chemistry Letters, 22 (2012) 3571–3574.
  • H. Lei, C. Li, Y. Yang, F. Jia, M. Guo, M. Zhu, N. Jiang, X. Zhai, Structure guided design of potent indole-based ATX inhibitors bearing hydrazone moiety with tumor suppression effects, European Journal of Medicinal Chemistry, 201 (2020) 112456.
  • T.R.F. de Melo, R.C. Chelucci, M.E.L. Pires, L.A. Dutra, K.P. Barbieri, P.L. Bosquesi, G.H.G. Trossini, M.C. Chung, J.L. dos Santos, Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-acyl hydrazone subunit, International Journal of Molecular Sciences, 15 (2014) 5821–5837.
  • O. Ünsal-Tan, K. Özden, A. Rauk, A. Balkan, Synthesis and cyclooxygenase inhibitory activities of some N-acylhydrazone derivatives of isoxazolo[4,5-d]pyridazin-4(5H)-ones, European Journal of Medicinal Chemistry, 45 (2010) 2345–2352.
  • Z. Ju, M. Su, J. Hong, E. La Kim, H.R. Moon, H.Y. Chung, S. Kim, J.H. Jung, Design of balanced COX inhibitors based on anti-inflammatory and/or COX-2 inhibitory ascidian metabolites, European Journal of Medicinal Chemistry, 180 (2019) 86–98.
  • B. Liu, L. Qu, S. Yan, Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity, Cancer Cell International, 15 (2015) 1–7.
  • J. Zhang, B. Zhang, X. Li, X. Han, R. Liu, J. Fang, Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update, Medicinal Research Reviews, 39 (2019) 5–39.