Ternary copper(II) complex of 5-hydroxytryptophan and 1,10-phenanthroline with several pharmacological properties and an adequate safety profile

D?ALESSANDRO FRANCO; O.E.PIRO; P.A.M. WILLIAMS; J.J. MARTÍNEZ MEDINA; A. RIZZI; E.G. FERRER; L. NASO; REY M.; GUSTAVO ETCHEVERRÍA

JOURNAL OF INORGANIC BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2020 vol. 204

0162-0134

We report the synthesis and biological evaluation of a ternary copper complex, [Cu(5HTP)(phen)(H2O)](NO3).2H2O, with the antioxidant agent 5-hydroxytryptophan (5-HTP) and phenanthroline (phen, added to improve its lipophilicity and membrane transport). The crystal structure of the complex was determined by X-ray diffraction methods. The complex showed antioxidant, antimicrobial, antitumor and antimetastatic properties with an adequate safety profile. The interaction of the metal with phen promotes cellular copper accumulation and cytotoxicity on human lung A549 cell line (IC50 = 3.6 μM). Furthermore, the viability of the normal human fetal lung fibroblast cell line (MRC-5) is not altered by the complex. An oxidative stress mechanism for the anticancer effect has been determined: cellular increase of reactive oxygen species (ROS), decrease of the glutathione (GSH) and oxidized GSH (GSSG) ratio and alteration of the mitochondrial potential. The complex also displays antimetastatic activities with inhibition of cell adhesion, invasion and migration. It has not mutagenic behavior and no toxicity on Artemia salina indicating its potential to act as an effective and safety antimicrobial and antitumor drug.