Naphthoylhydrazones: coordination to metal ions and biological screening

Nadia Ribeiro, Adelino M. Galvão, Clara S. B. Gomes, Helena Ramos, Rute Pinheiro, Lucilia Saraiva, Epole Ntungwe, Vera Isca, Patricia Rijo, Isabel Cavaco, Filipa Ramilo-Gomes, Rita C. Guedes, João Costa Pessoa, Isabel Correia

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Abstract

We report the synthesis of 3-hydroxyl-2-naphthoylhydrazones containing pyrrole (HL1), furane (HL2) and thiophene (HL3) moieties and their V(IV)O-, Cu(II)- and Zn(II)-complexes. All compounds are characterized by the usual analytical techniques and coordination of the ligands to the metal ions is discussed based on spectroscopic data (FTIR, UV-vis, EPR and NMR) as well as CAMB3LYP DFT/TDDFT calculations, indicating the formation of neutral ML2 type complexes. The photophysical properties of ligands and complexes are disclosed. The binding to Bovine Serum Albumin (BSA) is evaluated in detail using several spectroscopic tools. Circular dichroism shows that the compounds, and particularly the ligand precursors, stabilize BSA, increasing its a-helical content. Fluorescence studies indicate the formation of 1 : 1 protein-compound adducts, which is corroborated by molecular docking studies that show the interaction between Trp 213 of BSA and the naphthalene rings. The general toxicity is evaluated using the Artemia salina lethality assay, with all compounds showing general toxicity towards the brine shrimp model. The cytotoxicity on human cancer cells (H1299, MCF7, and HCT116) is assessed for all compounds and the half-maximal inhibitory concentration (IC50) values are in the range from 0.57 to 27.35 mu M. Compounds containing L-1 (pyrrole derivative) are the most cytotoxic, with the vanadium and zinc complexes performing better than the copper ones, and some of them depicting IC50 values lower than 1.1 mM. However, selectivity needs improvement as the compounds show toxicity towards Artemia salina and normal fibroblasts.
Original languageEnglish
Pages (from-to)17801-17818
JournalNew Journal of Chemistry
Volume43
Issue number45
DOIs
Publication statusPublished - 7 Dec 2019

Cite this

Ribeiro, N., Galvão, A. M., Gomes, C. S. B., Ramos, H., Pinheiro, R., Saraiva, L., ... Correia, I. (2019). Naphthoylhydrazones: coordination to metal ions and biological screening. New Journal of Chemistry, 43(45), 17801-17818. https://doi.org/10.1039/c9nj01816f