A NEW MIXED LIGAND COPPER(II) COMPLEX OF NARINGENIN AS A PROSPECTIVE ANTICANCER AGENT

NASO, LUCIANA G.; CARO-RAMÍREZ, JANETSI Y.; EVELINA G. FERRER; WILLIAMS, PATRICIA A. M.

Congreso; Reunión de Sociedades de Biociencias 2021. SAIC-SAI-AAEF-Nanomed; 2021

Objective: The flavonoids can be chemically modified by complexation with metals to be applied for adjuvant therapy. In this context, we evaluated the anticancer activity on the lung cancer cell line A549 of CuNarBatho. Nar: naringenin, Batho: bathophenanthroline. Their bovine serum albumin (BSA) binding properties have also been evaluated.Methods: The effects of the compounds (CuNarBatho, CuNar, ligands and metal) on the A549 cell viability were measured by MTT assay. To evaluate the probable mechanism of action, morphological changes, intracellular reactive oxygen species ROS content (using CM-H2DCFDA probe), mitochondrial membrane potential (MMP) (using DIOC6 probe), and GSH depletion and cell viability in the presence of NAC were examined. The interaction between CuNarBatho and BSA was studied using tryptophan fluorescence quenching.Results: CuNarBatho was more efficient than Batho, and Nar in inhibiting A549 cell viability (IC50 values 0.3, 12.1 and > 100 µM respectively at 24 h incubation). CuNar slightly inhibited cell viability. The probable mechanism of action of the ternary complex implies increased ROS levels, reduced GSH and GSH/GSSG ratio levels, and decreased MMP. Also, increment of cytoplasm condensation and presence of pycnotic nuclei were observed. Upon addition of NAC, the anticancer effect has been reverted. The binding constant values (Kb) for the CuNarBatho-BSA system are 36.2, 14.9 and 2.3 × 105 M−1 at 298, 303 and 310 K suggesting that the compound can be stored and carried by the protein. The number of binding sites was ca. 1.0 corresponding to the binding sites with high affinity. The negative ΔH and ΔS values (-177.03 and -0.47 KJ/mol) obtained for the interaction of CuNarBatho with BSA indicated that hydrogen bonding and Van der Waals forces played major roles during the interaction. Discussion: The results suggest that the CuNarBatho complex could serve as a pharmacologically active compound for the treatment of lung cancer