Antitumoral effect of novel synthetic 8-hydroxy-2-((4-nitrophenyl)thio)naphthalene-1,4-dione (CNN16) via ROS-mediated DNA damage, apoptosis and anti-migratory effect in colon cancer cell line.

Colorectal cancer (CRC) is estimated as the third most incident cancer and second in mortality worldwide. Moreover, CRC metastasis reduces patients' survival rates. Thus, the study and identification of new compounds with anticancer activity selectively to tumor cells are encouraged in the CRC treatment. Naphtoquinones are compounds with several pharmacologic activities, including antitumoral properties. Therefore, this study aimed to investigate the anticancer mechanism of synthetic 8-Hydroxy-2-(P-Nitrothiophenol)-1,4-Naphthoquinone (CNN16) in colon cancer cell line HCT-116. CNN16 showed an IC50 of 5.32 µM in HCT-116, and 9.36, 10.77, and 24.57 µM in the non-cancerous cells MRC-5, MNP-01, and PMBC, respectively, evaluated by the MTT assay. CNN16 showed an anticlonogenic effect in HCT-116 and induced cell fragmentation identified by flow cytometry analysis. Furthermore, we observed that CNN16 presented genotoxicity and induces reactive oxygen species (ROS) after 3 h of treatment visualized by alkaline comet assay and DCFH-DA dye fluorescence, respectively. Furthermore, CNN16 caused cellular membrane disruption, reduction in the mitochondrial membrane polarization, and the presence of apoptotic bodies and chromatin condensation was visualized by differential stained (HO/FD/PI) in fluorescent microscopy along with PARP1, TP53, BCL-2, and BAX analyzed by RT-qPCR. Results also evidenced inhibition in the migratory process analyzed by wound healing assay. Therefore, CNN16 can be considered as a potential new leader molecule for CRC treatment, although further studies are still necessary to comprehend the effects of CNN16 in in vivo models to evaluate the anti-migratory effect, and toxicology and assure compound safety and selectively.

Evaluation of 5-hydroxy-1,4-naphthoquinone-cobalt(III) complexes for hypoxia-activated drug delivery.

Three novel Py2N2-cobalt(III) complexes with the 5-hydroxy-1,4-naphthoquinone nuclei (NQ) were evaluated as potential hypoxia-activated anticancer prodrugs. The complexes were synthesized and fully characterized by IR and UV-Visible spectroscopies, ESI mass spectrometry and CHN elemental analysis. Structural information was obtained from density functional theory (DFT) calculations. Cyclic voltammetry analysis in acetonitrile indicates that the ligand substituents (H, CH3 and p-tolylthio) do not have a relevant effect on the Co3+/Co2+ redox potential. Reactions with ascorbic acid in phosphate buffers were performed to simulate redox activation of the complexes in biological media. Fast and irreversible dissociation of the NQ ligands was observed for all complexes upon Co3+/Co2+ reduction. Cytotoxic activity of complexes 1 and 3 was evaluated in tumor cells (HT-29 and HCT-116) under hypoxic and normoxic conditions.