Synthesis, Characterization and Biological Activity of Novel Cu(II) Complexes of 6-Methyl-2-Oxo-1,2-Dihydroquinoline-3-Carbaldehyde-4n-Substituted Thiosemicarbazones
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
Affiliations
Eswaran Ramachandran
Department of Industrial Engineering, University of Padova, 35131 Padova, Italy
Valentina Gandin
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
Roberta Bertani
Department of Industrial Engineering, University of Padova, 35131 Padova, Italy
Paolo Sgarbossa
Department of Industrial Engineering, University of Padova, 35131 Padova, Italy
Karuppannan Natarajan
Department of Chemistry, Sri Ramakrishna Mission Vidyalaya College of Arts and Science, Coimbatore, Tamil Nadu 641020, India
Nattamai S. P. Bhuvanesh
Department of Chemistry, Texas A&M University, College Station, TX 77842, USA
Alfonso Venzo
Department of Chemical Sciences, University of Padova, 35131 Padova, Italy
Alfonso Zoleo
Department of Chemical Sciences, University of Padova, 35131 Padova, Italy
Mirto Mozzon
Department of Industrial Engineering, University of Padova, 35131 Padova, Italy
Alessandro Dolmella
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
Alberto Albinati
Department of Chemistry, University of Milan, 20133 Milan, Italy
Carlo Castellano
Department of Chemistry, University of Milan, 20133 Milan, Italy
Nuno Reis Conceição
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
M. Fátima C. Guedes da Silva
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
Cristina Marzano
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
Three new 6-methyl-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-thiosemicarbazones-N-4-substituted pro-ligands and their Cu(II) complexes (1, -NH2; 2, -NHMe; 3, -NHEt) have been prepared and characterized. In both the X-ray structures of 1 and 3, two crystallographically independent complex molecules were found that differ either in the nature of weakly metal-binding species (water in 1a and nitrate in 1b) or in the co-ligand (water in 3a and methanol in 3b). Electron Paramagnetic Resonance (EPR) measurements carried out on complexes 1 and 3 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 2 and 3 exhibited a high cytotoxicity against human tumor cells and 3D spheroids derived from solid tumors, related to the high cellular uptake. Complexes 2 and 3 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.
