Design concepts of half-sandwich organoruthenium anticancer agents based on bidentate bioactive ligands

William D.J. Tremlett, David M. Goodman, Tasha R. Steel, Saawan Kumar, Anna Wieczorek-Błauż, Fearghal P. Walsh, Matthew P. Sullivan, Muhammad Hanif, Christian G. Hartinger

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations

Abstract

The small molecule anticancer agent cisplatin and its Pt(II) analogs carboplatin and oxaliplatin are widely used to treat a variety of tumorigenic diseases. Despite their structural simplicity, side effects and disadvantages, they are cornerstones of cancer chemotherapy. Several strategies have been pursued to enhance the activity and reduce the side effects of metal-based drugs, for example, to use bioactive ligands that equip them with novel modes of action, enhance delivery, allow for selective activation, create synergistic effects or improve tumor accumulation. Many of these strategies have been developed for or adapted in the design of half-sandwich organoruthenium compounds. For such compounds decorated with bioactive ligands that coordinate monodentately to the Ru center, we have identified five design concepts (Coord. Chem. Rev. 2021, 439, 213890): (i) the bioactive ligand coordinates directly to the Ru center or (ii) after functionalization with a coordinating group, (iii) the ligand(s) and the Ru center solely define the overall shape of the molecule, (iv) the bioactive ligand is released, and (v) the bioactive ligand acts as a vector to the tumor (cell). Herein, we use these five concepts and explore their application to half-sandwich organoruthenium anticancer compounds in which the bioactive ligand is coordinated to the Ru center through a bidentate chelating motif.

Original languageEnglish
Article number213950
JournalCoordination Chemistry Reviews
Volume445
DOIs
StatePublished - 15 Oct 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • 16HBE
  • ARPE-19
  • African green monkey kidney cells
  • Anticancer agents
  • BEAS-2B
  • BGM
  • Bidentate bioactive ligands
  • Bioorganometallics
  • Buffalo Green Monkey kidney cells
  • CA-M75
  • CHO
  • Chinese hamster ovary cells
  • EA.hy 926
  • FG0
  • HEK
  • HEK-293 T, human embryonic kidney
  • HEK-293, human embryonic kidney
  • HEK-293T
  • HEK293
  • HFF-1
  • HL-7702
  • HLF
  • HUVEC
  • HaCaT
  • IMR-90
  • KMST-6
  • L929
  • LLC-PK1
  • MCF-10A
  • MDBK
  • MRC-5
  • MS1
  • Metallodrugs
  • Mode of action
  • NIH-3T3
  • PBMC
  • RAW264.7
  • Raw-264.7, mouse macrophage
  • Synergistic activity
  • Vero
  • bovine kidney epithelium
  • human breast epithelium
  • human embryonal lung fibroblast
  • human embryonic fibroblast
  • human embryonic kidney
  • human epidermal keratinocyte
  • human foreskin fibroblast
  • human liver cells
  • human lung bronchial epithelium
  • human lung fibroblast
  • human lung fibroblast-1
  • human peripheral blood mononuclear cells
  • human retinal pigment epithelium
  • human umbilical vein endothelium
  • lung epithelium
  • mouse embryonic fibroblast
  • mouse fibroblast
  • murine endothelium
  • pig kidney epithelium
  • skin fibroblasts
  • skin melanocyte
  • transformed human umbilical vein endothelium

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