Synthesis of isoflavene-thiosemicarbazone hybrids and evaluation of their anti-tumor activity

Eugene M H Yee; Miriam B Brandl; David StC Black; Orazio Vittorio; Naresh Kumar

doi:10.1016/j.bmcl.2017.04.002

Synthesis of isoflavene-thiosemicarbazone hybrids and evaluation of their anti-tumor activity

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2454-2458. doi: 10.1016/j.bmcl.2017.04.002. Epub 2017 Apr 3.

Authors

Eugene M H Yee¹, Miriam B Brandl², David StC Black¹, Orazio Vittorio², Naresh Kumar³

Affiliations

¹ School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
² Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia.
³ School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: n.kumar@unsw.edu.au.

PMID: 28408225
DOI: 10.1016/j.bmcl.2017.04.002

Abstract

Phenoxodiol is an isoflavene with potent anti-tumor activity. In this study, a series of novel mono- and di-substituted phenoxodiol-thiosemicarbazone hybrids were synthesized via the condensation reaction between phenoxodiol with thiosemicarbazides. The in vitro anti-proliferative activities of the hybrids were evaluated against the neuroblastoma SKN-BE(2)C, the triple negative breast cancer MDA-MB-231, and the glioblastoma U87 cancer cell lines. The mono-substituted hybrids exhibited potent anti-proliferative activity against all three cancer cell lines, while the di-substituted hybrids were less active. Selected mono-substituted hybrids were further investigated for their cytotoxicity against normal MRC-5 human lung fibroblast cells, which identified two hybrids with superior selectivity for cancer cells over normal cells as compared to phenoxodiol. This suggests that mono-substituted phenoxodiol-thiosemicarbazone hybrids have promising potential for further development as anti-cancer agents.

Keywords: Anti-cancer; Isoflavene; Phenoxodiol; Thiosemicarbazone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / toxicity
Benzopyrans / chemical synthesis
Benzopyrans / pharmacology*
Benzopyrans / toxicity
Cell Line, Tumor
Drug Screening Assays, Antitumor
Humans
Isoflavones / chemical synthesis
Isoflavones / pharmacology*
Isoflavones / toxicity
Thiosemicarbazones / chemical synthesis
Thiosemicarbazones / pharmacology*
Thiosemicarbazones / toxicity

Substances

Antineoplastic Agents
Benzopyrans
Isoflavones
Thiosemicarbazones
phenoxodiol