2. Academic Validation
  3. Synthesis of Sorafenib-Ruthenium Complexes, Investigation of Biological Activities and Applications in Drug Delivery Systems as an Anticancer Agent

Synthesis of Sorafenib-Ruthenium Complexes, Investigation of Biological Activities and Applications in Drug Delivery Systems as an Anticancer Agent

  • J Med Chem. 2024 Mar 12. doi: 10.1021/acs.jmedchem.3c01115.
Belma Zengin Kurt 1,  Dilek Öztürk Civelek 2,  Elmas Begüm Çakmak 3,  Yakup Kolcuoğlu 4,  Halil Şenol 1,  Begüm Nurpelin Sağlık Özkan 5,  Aydan Dag 1,  Kadriye Benkli 6
Affiliations

Affiliations

  • 1 Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Bezmialem Vakif University, 34093 Istanbul, Türkiye.
  • 2 Faculty of Pharmacy, Department of Pharmacology, Bezmialem Vakif University, 34093 Istanbul, Türkiye.
  • 3 Institute of Science, Sakarya University, 34000 Sakarya, Türkiye.
  • 4 Faculty of Science, Department of Chemistry, Karadeniz Technical University, 61080 Trabzon, Türkiye.
  • 5 Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University, 26470 Eskişehir, Türkiye.
  • 6 Badakbas Pharmacy, Altintepe str. Koknarli 6/C, Maltepe, 34840 Istanbul, Türkiye.
PMID: 38471014 DOI: 10.1021/acs.jmedchem.3c01115
Abstract

Sorafenib, a multiple kinase inhibitor, is widely used as a first-line treatment for hepatocellular carcinoma. However, there is a need for more effective alternatives when sorafenib proves insufficient. In this study, we aimed to design a structure that surpasses sorafenib's efficacy, leading us to synthesize sorafenib-ruthenium complexes for the first time and investigate their properties. Our results indicate that the sorafenib-ruthenium complexes exhibit superior epidermal growth factor receptor (EGFR) inhibition compared to sorafenib alone. Interestingly, among these complexes, Ru3S demonstrated high activity against various Cancer cell lines including sorafenib-resistant HepG2 cells while exhibiting significantly lower cytotoxicity than sorafenib in healthy cell lines. Further evaluation of cell cycle, cell Apoptosis, and antiangiogenic effects, molecular docking, and molecular dynamics studies revealed that Ru3S holds great potential as a drug candidate. Additionally, when free Ru3S was encapsulated into polymeric micelles M1, enhanced cytotoxicity on HepG2 cells was observed. Collectively, these findings position Ru3S as a promising candidate for EGFR inhibition and warrant further exploration for drug development purposes.

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