Synthesis and Characterisation of Novel Tricyclic and Tetracyclic Furoindoles: Biological Evaluation as SAHA Enhancer against Neuroblastoma and Breast Cancer Cells.

Abstract

The dihydropyranoindole structures were previously identified as promising scaffolds for improving the anti-cancer activity of histone deacetylase inhibitors. This work describes the synthesis of related furoindoles and their ability to synergize with suberoylanilide hydroxamic acid (SAHA) against neuroblastoma and breast cancer cells. The nucleophilic substitution of hydroxyindole methyl esters with α-haloketones yielded the corresponding arylether ketones, which were subsequently cyclized to tricyclic and tetracyclic furoindoles. The furoindoles showed promising individual cytotoxic efficiency against breast cancer cells, as well as decent SAHA enhancement against cancer cells in select cases. Interestingly, the best IC50 value was obtained with the non-cyclized intermediate.

• Authors: Murat Bingul, Greg M Arndt, Glenn M Marshall, David StC Black, Belamy B Cheung, Naresh Kumar
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 26 Issue 19 (Sep 22 2021) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 34641289 (Publication Type: Journal Article)

Chemical References

• Heterocyclic Compounds
• Histone Deacetylase Inhibitors
• Ketones
• Vorinostat

Topics

• Breast Neoplasms (drug therapy, enzymology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Synergism
• Female
• Heterocyclic Compounds (chemical synthesis, chemistry, pharmacology)
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• Ketones (chemical synthesis, chemistry, pharmacology)
• MCF-7 Cells
• Neuroblastoma (drug therapy, enzymology)
• Vorinostat (pharmacology)