Skip to main content
Applied Organometallic ChemistryVolume 37, Issue 1, January 2023, Article number e6922

New gold(III) chlorophenyl terpyridine complex: Biomolecular interactions and anticancer activity against human oral squamous cell carcinoma(Article)

  Save all to author list
  • aFaculty of Science, University of Kragujevac, Kragujevac, Serbia
  • bInstitute for Information Technologies, Department of Science, University of Kragujevac, Kragujevac, Serbia
  • cCenter for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
  • dDepartment of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

Abstract

In this work we synthesized new monofunctional gold(III) complex [Au(Cl-Ph-tpy)Cl]Cl2 (Cl-Ph-tpy = 4′-[4-chlorophenyl]-2,2′:6′, 2″-terpyridine). This complex was characterized by UV–Vis, NMR, IR, and ESI-MS spectrometry. The kinetic study of the substitution reactions of the Au-Cl-Ph-tpy complex with biomolecules showed that the rate constants depend on the nature of the entering nucleophile. Based on the calculated values of entropy (∆H≠ > 0) and enthalpy (∆S≠ < 0) the proposed substitution mechanism is associative. Additionally, the relative stability and thermodynamic properties of Au-Cl-Ph-tpy complex were compared with the analogue Au-tpy complex by the B3LYP/def2-svp method. DNA/BSA binding studies showed that Au-Cl-Ph-tpy complex interacts with CT DNA through the intercalation and moderately quenches the fluorescence of tryptophan residues in serum albumin (BSA). Molecular docking confirmed results obtained by spectroscopic experiments and suggested site I (subdomain IIA) for binding of Au complex to BSA. We demonstrated that the Au chlorophenyl terpyridine complex possessed significant in vitro cytotoxic activity against human oral squamous carcinoma cells (CAL-27), induced apoptosis, inhibited proliferation of CAL-27 cells, and induced cell cycle disturbance. Treatment of CAL-27 cells with the Au complex enhanced expression of cyclin-dependent kinase inhibitors p21 and p27, resulting in cell cycle arrest in the G1 phase, reduced the percentage of CAL-27 cells in S phase and decreased expression of Ki-67. Additionally, Au complex reduced expression of phosphorylated STAT3 and downstream regulated molecules associated with cancer stemness, NANOG, and Sox2 protein. © 2022 John Wiley & Sons Ltd.

Author keywords

apoptosisbiomolecularcancer stemnessdocking simulationsgold(III) complex

Indexed keywords

Engineering controlled terms:Amino acidsBiomoleculesDiseasesGold compoundsRate constantsSubstitution reactionsThermodynamic properties
Engineering uncontrolled termsAnticancer activitiesAu-complexesBio-molecularBiomolecular interactionsCancer stemnessDocking simulationsGold(III) complexInteraction activitiesOral squamous cell carcinomataTerpyridines
Engineering main heading:Cell death

Funding details

Funding sponsor Funding number Acronym
JP 1919,JP18/19,MP 0219
Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja062018,451‐03‐68/2022‐14/200122,451‐03‐68/2022‐14/200378,ON175069MPNTR
Ministarstvo Prosvete, Nauke i Tehnološkog RazvojaMPNTR
Childhood Cancer CanadaCCC

  • 1

    The authors are grateful to the Ministry of Education, Science and Technological Development of the Republic of Serbia (Agreement No. 451‐03‐68/2022‐14/200378, Agreement No. 451‐03‐68/2022‐14/200122 and ON175069), the bilateral project with PR China (062018), and the Faculty of Medical Sciences of the University of Kragujevac, Serbia (MP 0219 and JP18/19, JP 1919) for financial support. D.Ć. would like to thank Prof. Tim Clark and Prof. Petra Imhof for hosting this work at the CCC. D.Ć. gratefully acknowledge the Regionales Rechenzentrum Erlangen (RRZE) for a generous allotment of computer time. / / /

  • 2

    The authors are grateful to the Ministry of Education, Science and Technological Development of the Republic of Serbia (Agreement No. 451-03-68/2022-14/200378, Agreement No. 451-03-68/2022-14/200122 and ON175069), the bilateral project with PR China (06/2018), and the Faculty of Medical Sciences of the University of Kragujevac, Serbia (MP 02/19 and JP18/19, JP 19/19) for financial support. D.Ć. would like to thank Prof. Tim Clark and Prof. Petra Imhof for hosting this work at the CCC. D.Ć. gratefully acknowledge the Regionales Rechenzentrum Erlangen (RRZE) for a generous allotment of computer time.

  • ISSN: 02682605
  • CODEN: AOCHE
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1002/aoc.6922
  • Document Type: Article
  • Publisher: John Wiley and Sons Ltd

  Kesić, A.; University of Kragujevac, Institute for Information Technologies Kragujevac, Department of Natural Sciences, Jovana Cvijića bb, Kragujevac, Serbia;
  Simović, A.R.; University of Kragujevac, Institute for Information Technologies Kragujevac, Department of Natural Sciences, Jovana Cvijića bb, Kragujevac, Serbia;
© Copyright 2023 Elsevier B.V., All rights reserved.

Cited by 8 documents

Malarz, K. , Ziola, P. , Zych, D.
Imbalance of redox homeostasis and altered cellular signaling induced by the metal complexes of terpyridine
(2024) Scientific Reports
Gamov, G.A.
Complexation of Gold(I) and Gold(III) in solutions
(2024) Coordination Chemistry Reviews
Huang, X. , Wang, B. , Sun, D.
Synthesis of substituted terpyridine nickel nitrate complexes and their inhibitory selectivity against cancer cell lines
(2024) Journal of Inorganic Biochemistry
View details of all 8 citations
Inform me when this document is cited in Scopus:
Set citation alert Set citation feed
{"topic":{"name":"Anticarcinogen; Coordination Compound; Drug Screening","id":11054,"uri":"Topic/11054","prominencePercentile":95.20547,"prominencePercentileString":"95.205","overallScholarlyOutput":0},"dig":"36c82bf1cbae71f7020085bbcdaeddc6f846dfb104a7123e23a33366786985e1"}

SciVal Topic Prominence

Topic:
Prominence percentile: