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


ZENGİN KURT B., ÖZTÜRK CİVELEK D., Çakmak E. B., KOLCUOĞLU Y., ŞENOL H., SAĞLIK ÖZKAN B. N., ...Daha Fazla

JOURNAL OF MEDICINAL CHEMISTRY, cilt.67, sa.6, ss.4463-4482, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 67 Sayı: 6
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1021/acs.jmedchem.3c01115
  • Dergi Adı: JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Veterinary Science Database
  • Sayfa Sayıları: ss.4463-4482
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

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.