INHIBITORY EFFECT OF COUMARIN BENZOYLHYDRAZONES ON MCL-1 PROTEIN

1st International Conference on Chemo and BioInformatics, ICCBIKG  2021, (442-445)

AUTHOR(S) / АУТОР(И): Dušica M. Simijonović, Marko R. Antonijević, Edina H. Avdović, Zorica D. Petrović, Zoran S. Marković

E-ADRESS / Е-АДРЕСА: dusicachem@kg.ac.rs, mantonijevic@uni.kg.ac.rs, edina.avdovic@pmf.kg.ac.rs, zmarkovic@uni.kg.ac.rs, zorica.petrovic@pmf.kg.ac.rs

Download Full Pdf   

DOI: 10.46793/ICCBI21.442S

ABSTRACT / САЖЕТАК:

The protein that controls cell differentiation in acute myeloid leukemia is MCL-1. High-level of this protein causes the carcinogenesis. In this paper inhibitory effect of two coumarin benzoylhydrazones,(E)-2-hydroxy-N’-(1-(2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (A) and (E)-4-hydroxy-N’-(1-(2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (B) against MCL-1 protein was investigated. For this purpose, a molecular docking simulations were used. The obtained results showed that compound A showed better activity than compound B. Also, the docking simulations against MCL-1 protein were performed for melphalan or (2S)-2-amino- 3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid and two 4-chlorocoumarin benzoylhydrazone derivatives, N′-[(E)-(4-chloro-2-oxo-2H-chromen-3-yl)- methylidene]benzohydrazide (4a) and N′-[(E)-(4-chloro-2-oxo-2H-chromen-3-yl)- methylidene]-4-hydroxybenzohydrazide (4b). In this study, melphalan as a chemotherapy drug commonly used in treating multiple myeloma and compounds 4a and 4b as structurally similar compounds with A and B were used as reference compounds. It was shown that these reference compounds exhibited similar activity as compound B. In addition, the potential toxicology of compounds A and B, as well as reference compounds was determined by the ProTox-II webserver. The results revealed that compounds A and B are 3 to 5 times lower toxic than reference compounds.

KEY WORDS / КЉУЧНЕ РЕЧИ:

Molecular docking, Acute myeloid leukemia, Coumarin benzoylhydrazones.

REFERENCES / ЛИТЕРАТУРА:

  • S. Weinmamm, In Coumarins: Biology, Applications and Modes of Actions, R. O’Kennedy, R.D. Thornes, Eds.; John Wiley: England, (1997) pp 1-2.
  • S. Kirkiacharian, D.T. Thuy, S. Sicsic, R. Bakhchinian, R. Kurkjian, T. Tonnaire, Structure-activity relationships of some 3-substituted-4-hydroxycoumarins as HIV-1 protease inhibitors, Farmaco 57 (2002) 703-708.
  • S. V. Stanchev, T. Hadjimitova, T. Traykov, I. Boyanov, I. Manolov, Investigation of the antioxidant properties of some new 4-hydroxycoumarin derivatives, European Journal of Medicinal Chememistry, 44 (2009) 3077-3082.
  • Manolov, C. Maichle-Moessmer, N. Danchev, Synthesis, structure, toxicological and pharmacological investigations of 4-hydroxycoumarin derivatives, European Journal of Medicinal Chemistry, 41 (2006) 882-890.
  • Q. G. Ji, Z.Q. Ge, Z.X. Ge, K.Z. Chen, H.L. Wu, X.F. Liu, Y.R. Huang, L.J. Yuan, X.L. Yang, F. Liao, Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents, European Journal of Medicinal Chemistry, 108 (2016) 166-176.
  • S. Rahmani-Nezhad, M. Safavi, M. Pordeli, S. Ardestani, L. Khosravani, Y. Pourshojaei, Mahdavi, S. Emami, A. Foroumadi, A. Shafiee, Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents, European Journal of Medicinal Chemistry, 86 (2014) 562-569.
  • C. Congiu, V. Onnis, Synthesis and biological evaluation of novel acylhydrazone derivatives as potential antitumor agents, Bioorganic Medicinal Chemistry 21 (2013) 6592-6599.
  • V. T. Angelova, N.G. Vassilev, B. Nikolova-Mladenova, J. Vitas, R. Malbaša, G. Momekov, M. Djukic, L. Saso, Antiproliferative and antioxidative effects of novel hydrazone derivatives bearing coumarin and chromene moiety, Medicinal Chemistry Research, 25 (2016) 2082-2092.
  • Pangal, J. A. Shaikh, G. Muiz, V. Mane, K. Ahmed, Novel 3-acetylcoumarin Schiff̓s base synthesisfrom different acid hydrazide, International Research Journal of Pharmacy, 10 (2014) 108-110.
  • P. A. Ravindranath, S. Forli, D.S. Goodsell, A.J. Olson, M.F. Sanner, AutoDockFR: Advances in Protein-Ligand Docking with Explicitly Specified Binding Site Flexibility, PLoS Comput. Biol. 11 (2015). https://doi.org/10.1371/journal.pcbi.1004586.
  • M. J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, et al., Gaussian 09, (2009). http://www.gaussian.com.
  • Banerjee, Priyanka, Andreas O. Eckert, Anna K. Schrey, and Robert Preissner. „ProTox- II: a webserver for the prediction of toxicity of chemicals.“ Nucleic acids research 46, no. W1 (2018): W257-W263.