Synthesis, characterization and multiple targeting with selectivity: Anticancer property of ternary metal phenanthroline-maltol complexes

• Main Authors: Ng, Chew Hee, Tan, Thean Heng, Tioh, Ngee Heng, Seng, Hoi Ling, Ahmad, Munirah, Ng, Seik Weng, Gan, Wei Khang, Low, May Lee, Lai, Jing Wei, Zulkefeli, Mohd
• Format: Article
• Published: 2021
• Subjects: Q Science (General); QD Chemistry
• Online Access: http://eprints.um.edu.my/26211/; https://doi.org/10.1016/j.jinorgbio.2021.111453

The cobalt(II), copper(II) and zinc(II) complexes of 1,10-phenanthroline (phen) and maltol (mal) (complexes 1, 2, 3 respectively) were prepared from their respective metal(II) chlorides and were characterized by FT-IR, elemental analysis, UV spectroscopy, molar conductivity, p-nitrosodimethylaniline assay and mass spectrometry. The X-ray structure of a single crystal of the zinc(II) analogue reveals a square pyramidal structure with distinctly shorter apical chloride bond. All complexes were evaluated for their anticancer property on breast cancer cell lines MCF-7 and MDA-MB-231, and normal cell line MCF-10A, using (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide assay and morphological studies. Complex 2 was most potent for 24, 48 and 72 h treatment of cancer cells but it was not selective towards cancer over normal cells. The mechanistic studies of the cobalt(II) complex 1 involved apoptosis assay, cell cycle analysis, dichloro-dihydro-fluorescein diacetate assay, intracellular reactive oxygen species assay and proteasome inhibition assay. Complex 1 induced low apoptosis, generated low level of ROS and did not inhibit proteasome in normal cells. The study of the DNA binding and nucleolytic properties of complexes 1-3 in the absence or presence of H2O2 or sodium ascorbate revealed that only complex 1 was not nucleolytic.