Screening the biological properties of transition metal carbamates reveals gold(I) and silver(I) complexes as potent cytotoxic and antimicrobial agents

J Inorg Biochem. 2022 Feb:227:111667. doi: 10.1016/j.jinorgbio.2021.111667. Epub 2021 Nov 18.

Abstract

We report a screening study aimed to assess for the first time the air- and water-stability and the biological potential of simple metal-carbamates. These molecular metallic species are based on elements belonging to the groups 4-5, 7-9 and 11, and tin, and are easily available from inexpensive reagents. Complexes [Ag(O2CNEt2)] (13-Ag) and [Au(O2CNMe2)(PPh3)] (14-Au) resulted substantially stable in aqueous media and exhibited a potent in vitro cytotoxicity. Especially 13-Ag revealed a significant selectivity against the A549 lung adenocarcinoma and the A2780 ovarian cancer cell lines with respect to the noncancerous HEK293 cell line. Generation of ROS (reactive oxygen species) and mitochondrial membrane depolarization were recognized for 13-Ag and 14-Au; notwithstanding, the cell death mechanism is different in the two cases: apoptosis and cell cycle arrest in G0/G1 phase for 13-Ag; necroptosis and cell cycle arrest in S phase for 14-Au. Both 13-Ag and 14-Au are endowed with antibacterial activity, which is relatively stronger for 13-Ag towards Gram negative and for 14-Au towards Gram positive strains, respectively.

Keywords: Antibacterial activity; Anticancer metal complexes; Cytotoxicity; Metal carbamates; Metals in medicine; Transition metal complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Anti-Infective Agents* / chemistry
  • Anti-Infective Agents* / pharmacology
  • Apoptosis / drug effects
  • Carbamates* / chemistry
  • Carbamates* / pharmacology
  • Cell Cycle Checkpoints / drug effects
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Cytotoxins* / chemistry
  • Cytotoxins* / pharmacology
  • Gold* / chemistry
  • Gold* / pharmacology
  • HEK293 Cells
  • Humans
  • Necroptosis / drug effects
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Silver* / chemistry
  • Silver* / pharmacology

Substances

  • Anti-Infective Agents
  • Carbamates
  • Coordination Complexes
  • Cytotoxins
  • Silver
  • Gold