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

Abstract

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 IC 50 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.

Germanium‐based monoelemental and binary two‐dimensional materials: Theoretical and experimental investigations and promising applications

“…The daily intake of Ge from food is estimated to be 367–3700 mg, 584 and both organic and inorganic Ge compounds have a long history as dietary supplements 585 . Some Ge‐based drugs have also been clinically approved for the treatment of various diseases, such as arthritis and cancer 586–590 . Therefore, the special superiorities of Ge highlight the biosafety, biocompatibility, and potential biomedical value of exploiting Ge‐based 2D materials.…”

“…585 Some Ge-based drugs have also been clinically approved for the treatment of various diseases, such as arthritis and cancer. [586][587][588][589][590] Therefore, the special superiorities of Ge highlight the biosafety, biocompatibility, and potential biomedical value of exploiting Ge-based 2D materials.…”

A Review on the Recent Advancements on Therapeutic Effects of Metallic Ions in the Physiological Environments

“…They attack and kill the host cells, resulting in the activation of other immune cells. Thus, cytokines are produced, and other cells of the immune system are influenced due to the production of circulating lymphokines [87]. Activated macrophages were generated from resting macrophages by these lymphokine(s).…”

On the Origin of Reduced Cytotoxicity of Germanium-Doped Diamond-Like Carbon: Role of Top Surface Composition and Bonding

“…Germanium is considered to be a nonessential element with low acute toxicity. Ge exerts prophylactic and therapeutic effects in the treatments of cancer and Human immunodeficiency Virus (HIV) infections [10][11][12], immune activation effects for bio-germanium [13], and antioxidant effects [14]. Ge-containing dietary supplements were widely used in the 1970s in Japan and later in other countries to promote health and cure diseases.…”