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2000
Volume 16, Issue 4
  • ISSN: 1573-4072
  • E-ISSN: 1875-6646

Abstract

Background: A green and efficient synthetic methodology for a wide family of Nacylhydrazones (yields: 42-76%) using microwave irradiation is described, as well as their full characterization. Their potential antineoplastic activity was evaluated in vitro via EMSA by testing protein- DNA interactions. Among the 11 compounds tested, N-acylhydrazone derivative 5 bearing a hydroxyl group, showed the highest affinity to bind and inhibit the hnRNP K KH3 domain. Docking simulations of compound 5 showed three possible modes of interaction between the KH3 domain of hnRNP K protein and compound predict. The N-acylhydrazones are knows as powerful chemical entities for Medicinal Chemistry, since it has been identified in a huge number of hit and lead compounds that act on various types of molecular targets, including in tumorigenesis processes. Objective: We evaluated their potential ability to inhibit the KH3 domain of the hnRNP K protein binding to single stranded DNA (ssDNA). Furthermore, a docking simulation was performed for the newly synthetized compounds to evaluate their interactions between proteins and N-acylhydrazine derivative. Methods: The N-acylhydrazone derivatives were synthetized through three reaction steps, from a simple and commercial substrate, using microwave irradiation as a green energy source. The N-acylhydrazone derivatives ability to bind with the hnRNP K protein was evaluated via EMSA by testing protein-DNA interactions. The docking simulations were performed in a Gold 5.2.2 software using 100 conformers, 10.000 operations, 95 mutations and 95 crossovers. Results: Eleven new N-acylhydrazone derivatives were synthetized using microwave showing yields between 42% and 76%. Among the eleven compounds tested, compound 5 was shown to be most capable to prevent the natural binding of hnRNP K protein to the oligonucleotide. Regarding the docking simulation, compound 5 can bind to the main binding residues of KH3 domain and compete with the natural ligand ssDNA of this protein. Conclusion: A green and efficient synthetic methodology for a wide family of N-acylhydrazones (yields: 42-76%) using microwave irradiation is described, as well as their full characterization. Their potential antineoplastic activity was evaluated in vitro via EMSA by testing protein-DNA interactions. Among the 11 compounds tested, N-acylhydrazone derivative 5 bearing a hydroxyl group, showed the highest affinity to bind and inhibit the hnRNP K KH3 domain. Docking simulations of compound 5 showed three possible modes of interaction between the KH3 domain of hnRNP K protein and compound predict.

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/content/journals/cbc/10.2174/1573407215666190131121059
2020-06-01
2025-07-05
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  • Article Type:
    Research Article
Keyword(s): antineoplastic activity; cancer; docking; KH3 domain; N-acylhydrazones; Protein hnRNP K
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