Synthesis, Characterization and Biological Activity of Novel Cu(II) Complexes of 6-Methyl-2-Oxo-1,2-Dihydroquinoline-3-Carbaldehyde-4n-Substituted Thiosemicarbazones

• Main Authors: Eswaran Ramachandran, Valentina Gandin, Roberta Bertani, Paolo Sgarbossa, Karuppannan Natarajan, Nattamai S.P. Bhuvanesh, Alfonso Venzo, Alfonso Zoleo, Mirto Mozzon, Alessandro Dolmella, Alberto Albinati, Carlo Castellano, Nuno Reis Conceição, M. Fátima C. Guedes da Silva, Cristina Marzano
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Molecules
• Subjects: copper thiosemicarbazones complexes; X ray crystal structure; cytotoxicity in 3D spheroids; EPR and electrochemical measurements; TEM images
• Online Access: https://www.mdpi.com/1420-3049/25/8/1868

Three new 6-methyl-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-thiosemicarbazones-N-4-substituted pro-ligands and their Cu(II) complexes (<b>1</b>, -NH₂; <b>2</b>, -NHMe; <b>3</b>, -NHEt) have been prepared and characterized. In both the X-ray structures of <b>1</b> and <b>3</b>, two crystallographically independent complex molecules were found that differ either in the nature of weakly metal-binding species (water in <b>1a</b> and nitrate in <b>1b</b>) or in the co-ligand (water in <b>3a</b> and methanol in <b>3b</b>). Electron Paramagnetic Resonance (EPR) measurements carried out on complexes <b>1</b> and <b>3</b> confirmed the presence of such different species in the solution. The electrochemical behavior of the pro-ligands and of the complexes was investigated, as well as their biological activity. Complexes <b>2</b> and <b>3</b> exhibited a high cytotoxicity against human tumor cells and 3D spheroids derived from solid tumors, related to the high cellular uptake. Complexes <b>2</b> and <b>3</b> also showed a high selectivity towards cancerous cell lines with respect to non-cancerous cell lines and were able to circumvent cisplatin resistance. Via the Transmission Electron Microscopy (TEM) imaging technique, preliminary insights into the biological activity of copper complexes were obtained.