Abstract
BackgroundLiver 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.ResultsThe 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.ConclusionsThis 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.
Highlights
Cancer is one of the most deadly diseases worldwide and in the last years approximately 9 million deaths were estimated because of this disease [1, 2]
It was reported that the indole-containing hybrid compounds were shown inhibitory activity on CDK1 with 50% Inhibition concentration (IC50) 1.14 μM [21], significant antiproliferative activities on various kinds of cancer cell lines [22]
Kamal et al [23] reported an isoxazole-2,3-dihydroquinazolinone hybrid as cycline B1/ CDK1 inhibitor and this hybrid compound was effective against 18 human cancer cell lines
Summary
The cytotoxic activity was performed against Huh, MCF7 and HCT116 cancer cell lines using sulforho‐ damine 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 Huh cells and caused a significant decrease in CDK4 levels. A good cor‐ relation 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
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