PO-417 Synthesis of CU(II) complexes derived from imidazole and cytotoxic activity evaluation against breast and colorectal cancers

Abstract

IntroductionDespite the existence of new therapeutic options, breast (BC) and colorectal (CC) cancers remain the leading causes of cancer death and the most commonly diagnosed in worldwide. Studies have reported that imidazole derivates show anticancer, antimicrobial, antibacterial, antifungal and antioxidant activities. Furthermore, recently it has been found that the association between imidazole ligands and copper increases their DNA binding affinity giving potential anticancer activity. Therefore, we synthesised three novel Cu(II) complexes using heterocyclic nitroimidazole derivatives as ligands. The aim of this study is to evaluate the cytotoxic activity of these complexes in two BC and two CC cell lines.Material and methodsNitroimidazole derived ligands containing cyclohexylamine, morpholine and piperidine and the respective Cu(II) complexes were synthesised. MCF-7, HCC1806, LS1034 and WiDr cell lines were cultured and grown in proper conditions. To evaluate the cytotoxic activity of these Cu(II) complexes on four cell lines, MTT colorimetric assay was used. Cells were seeded in 48 well-plates and then were treated with increasing concentrations of the complexes, from 0.5 to 200 µM. After 48 hour of incubation, medium was removed and MTT was added. Two hours later, isopropanol was added in order to dissolve formazan crystals. The absorbance was read at 570 and 620 nm and IC50 (half maximal inhibitory concentration) values determined.Results and discussionsSome Cu(II) complexes exhibit anticancer activity in cell lines. Studies show that for the MCF-7 and LS1034 cell lines, the nitroimidazole derived complex containing cyclohexylamine presents IC50 values of 22.2 and 23.9 µM, respectively. For WiDr cell line, the same complex has an IC50 of 50.5 µM. The best IC50 value (2.9 µM) for this complex occurs in the HCC1806 cell line, a chemoresistant BC cell line.Curiously, the complex containing piperidine presents a IC50 of 3.8 µM in HCC1806 cell line, while in the other BC cell line (MCF-7) there is no anticancer activity.The nitroimidazole derived complex containing cyclohexylamine is, consequently, the most promising compound in four cell lines.ConclusionCu(II) complexes derived from nitroimidazole presented anticancer activity against all cell lines. The complex containing cyclohexylamine revealed to be the most promising, especially in HCC1806, basaloid triple-negative breast cancer, known as therapy-resistant.