Affiliations 

  • 1 Department of Chemistry, Quaid-i-Azam University, 45320, Islamabad, Pakistan. zrehman@qau.edu.pk hafizqau@yahoo.com
  • 2 Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK
  • 3 Department of Chemistry, University College London, 20 Gordon Street, London, WC1 0AJ, UK
  • 4 Institute of Marine Biotechnology, University Malaysia Terengganu, Kuala Terengganu, 21030, Malaysia
  • 5 Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec, H3A 0B8, Canada
  • 6 Département de Chimie, Université de Montréal, Montreal, Canada
  • 7 University of Hawaii at Hilo, The Daniel K. Inouye College of Pharmacy, USA
Dalton Trans, 2020 Nov 10;49(43):15385-15396.
PMID: 33140800 DOI: 10.1039/d0dt03018j

Abstract

The syntheses of two platinum(ii) dithiocarbamate complexes (1 and 2) that show quinoplatin- and phenanthriplatin-type axial protection of the Pt-plane are described. The Pt-plane of complex 2 is axially more protected than that of complex 1. Furthermore, both complexes adopt two different stereochemical conformations in the solid state (based on single-crystal X-ray structures) owing to the structurally flexible piperazine backbone; i.e., C-e,e-Anti (1) and C-e,a-Syn (2), where "C" stands for the chair configuration, "e" and "a" stand for the equatorial and axial positions and "Anti" (opposite side) and "Syn" (same side) represent the relative orientations in space of the terminal substituents on the piperazine ring. In complex 2, the C-e,a-Syn conformation may provide additional steric hindrance to the Pt-plane. Despite the lower lipophilicity of 2 as compared to that of 1, the in vitro anticancer action against selected cancer cell lines is better for the former revealing the superior role of the axial protection over lipophilicity in modulating anticancer activity. The activity against the cancer promoting protein NF-κB signifies that the mode of cancer cell death may be the result of hindering the activity of NF-κB in the initiation of apoptosis. The apoptotic mode of cell death has been established earlier in a study using Annexin V-FITC. Finally, DNA binding studies revealed that the complex-DNA adduct formation is spontaneous and the mode of interaction is non-intercalative (electrostatic/covalent).

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.