Interfering with Metabolic Profile of Triple-Negative Breast Cancers Using Rationally Designed Metformin Prodrugs

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

5 Scopus Citations
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Author(s)

  • Kai Ren Chong
  • Peter Rapta
  • Markella Zannikou
  • Hui Min Tang
  • Lisa Reichert
  • Meng Rui Chang
  • Vladimir Kushnarev
  • Petra Heffeter
  • Samuel M. Meier-Menches
  • Zhi Chiaw Lim
  • Jian Yu Yap
  • Angela Casini
  • Irina V. Balyasnikova
  • Wee Han Ang

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)13405-13413
Number of pages10
Journal / PublicationAngewandte Chemie - International Edition
Volume60
Issue number24
Online published23 Mar 2021
Publication statusPublished - 7 Jun 2021

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by an aberrant metabolic phenotype with high metastatic capacity, resulting in poor patient prognoses and low survival rates. We designed a series of novel AuIII cyclometalated prodrugs of energy-disrupting Type II antidiabetic drugs namely, metformin and phenformin. Prodrug activation and release of the metformin ligand was achieved by tuning the cyclometalated AuIII fragment. The lead complex 3met was 6000-fold more cytotoxic compared to uncoordinated metformin and significantly reduced tumor burden in mice with aggressive breast cancers with lymphocytic infiltration into tumor tissues. These effects was ascribed to 3met interfering with energy production in TNBCs and inhibiting associated pro-survival responses to induce deadly metabolic catastrophe.

Research Area(s)

  • antitumor agents, drug discovery, metabolism, metformin, prodrugs

Citation Format(s)

Interfering with Metabolic Profile of Triple-Negative Breast Cancers Using Rationally Designed Metformin Prodrugs. / Babak, Maria V.; Chong, Kai Ren; Rapta, Peter; Zannikou, Markella; Tang, Hui Min; Reichert, Lisa; Chang, Meng Rui; Kushnarev, Vladimir; Heffeter, Petra; Meier-Menches, Samuel M.; Lim, Zhi Chiaw; Yap, Jian Yu; Casini, Angela; Balyasnikova, Irina V.; Ang, Wee Han.

In: Angewandte Chemie - International Edition, Vol. 60, No. 24, 07.06.2021, p. 13405-13413.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review