Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines
BMC Chemistry, cilt.15, sa.1, 2021 (Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 15 Sayı: 1
- Basım Tarihi: 2021
- Doi Numarası: 10.1186/s13065-021-00793-8
- Dergi Adı: BMC Chemistry
- Derginin Tarandığı İndeksler: Scopus
- Anahtar Kelimeler: Indole, Isoxazole, Hepatocellular carcinoma, Cell cycle arrest, Apoptosis, CDK4
- Hacettepe Üniversitesi Adresli: Evet
Özet
Background: Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth leading cause of cancer deaths. In this study, a series of indole-3-isoxazole-5-carboxamide derivatives were designed, synthesized, and evaluated for their anticancer activities. The chemical structures of these of final compounds and intermediates were characterized by using IR, HRMS, 1H-NMR and 13C-NMR spectroscopy and element analysis. Results: The cytotoxic activity was performed against Huh7, MCF7 and HCT116 cancer cell lines using sulforhodamine B assay. Some compounds showed potent anticancer activities and three of them were chosen for further evaluation on liver cancer cell lines based on SRB assay and real-time cell growth tracking analysis. Compounds were shown to cause arrest in the G0/G1 phase in Huh7 cells and caused a significant decrease in CDK4 levels. A good correlation was obtained between the theoretical predictions of bioavailability using Molinspiration calculation, Lipinski’s rule of five, and experimental verification. These investigations reveal that indole-isoxazole hybrid system have the potential for the development of novel anticancer agents. Conclusions: This study has provided data that will form the basis of further studies that aim to optimize both the design and synthesis of novel compounds that have higher anticancer activities.