Exploring six-coordinate germanium(IV)-diketonate complexes as anticancer agents

Cancer remains one of the leading causes of death worldwide and despite several attempts using chemotherapy to combat the deadly disease, toxic side effects and drug resistance temper efficacy [1]. Thus, drugs with potentially new mechanisms and lower toxicity to normal cells are needed. Metalloids such as arsenic compounds have been clinically beneficial in fighting cancer, but germanium is yet to gain such prominence [2,3]. We report the synthesis of four octahedral germanium(IV) complexes bearing acetylacetonato ligand, [Ge^IV(acac)₃)]⁺, with different anions (3 - 6) using a streamlined synthetic approach. The compounds were structurally and electrochemically characterized using NMR, MS, X-ray crystallography, and cyclic voltammetry. The cyclic voltammogram of 3-5 revealed distinct irreversible peaks in the range of -0.9 to -1.9 V, corresponding to Ge(IV)/ Ge(II) or Ge(II)/Ge(0) couple in DMSO. We explored the anticancer activity of the complexes against a panel of cancer cell lines with IC₅₀ values in the sub-micromolar range (9-15 μM). The compounds display ~3-fold selectivity in cancer cells over normal epithelial cells. In addition to the promising anticancer activity, the compounds display high complex stability in biological media, induces G1 arrest, reactive oxygen stress (ROS) accumulation, and mitochondria membrane depolarization in cancer cells. Furthermore, the compounds induce significant apoptosis.