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Updated: May 17, 2026
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and investigation of the anticancer effects of estrone-16-oxime ethers in vitro
Ágnes Berényi1, Renáta Minorics, Zoltán Iványi
1Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
Abstract:
An expanding body of evidence indicates the possible role of estrane derivatives as useful anticancer agents. The aim of this study was to describe the cytotoxic effects of 63 newly synthetized estrone-16-oxime ethers on human cancer cell lines (cervix carcinoma HeLa, breast carcinoma MCF7 and skin epidermoid carcinoma A431), studied by means of the MTT assay. Four of the most promising compounds were selected for participation in additional experiments in order to characterize the mechanism of action, including cell cycle analysis, morphological study and the 5-bromo-2'-deoxyuridine incorporation assay. The cancer selectivity was tested on a noncancerous fibroblast cell line (MRC-5). Since apoptosis and cell cycle disturbance were observed, caspase-3 activities were further assayed for the two most effective agents. These estrone-16-oxime analogs activated caspase-3 and changed the mRNA level expression of endogenous factors regulating the G1-S phase transition (retinoblastoma protein, CDK4 and p16). The repression of retinoblastoma protein was reinforced at a protein level too. These experimental data lead to the conclusion that estrone-16-oxime ethers may be regarded as potential starting structures for the design of novel anticancer agents.
Insights
Newly synthesized estrone-16-oxime ethers show significant anticancer potential. These compounds induce apoptosis and cell cycle arrest in cancer cells, offering a promising foundation for new cancer therapies.
Area of Science:
- Medicinal Chemistry
- Oncology
- Molecular Biology
Background:
- Estrane derivatives are increasingly recognized for their potential as anticancer agents.
- Estrone-16-oxime ethers represent a novel class of compounds with unexplored therapeutic applications.
Purpose of the Study:
- To synthesize and evaluate the cytotoxic effects of 63 novel estrone-16-oxime ethers against human cancer cell lines.
- To investigate the mechanism of action and cancer selectivity of the most promising compounds.
Main Methods:
- Cytotoxicity was assessed using the MTT assay on HeLa, MCF7, and A431 cancer cell lines.
- Mechanism of action was explored via cell cycle analysis, morphological studies, and 5-bromo-2'-deoxyuridine incorporation assays.
- Cancer selectivity was evaluated against noncancerous MRC-5 fibroblast cells.
Main Results:
- Four estrone-16-oxime ether derivatives exhibited significant cytotoxic activity.
- These compounds induced apoptosis and cell cycle arrest at the G1-S phase transition.
- Apoptosis was confirmed by caspase-3 activation and modulation of key regulatory proteins (retinoblastoma protein, CDK4, p16) at both mRNA and protein levels.
Conclusions:
- Estrone-16-oxime ethers demonstrate potent anticancer activity and selectivity.
- These compounds represent promising lead structures for the development of novel anticancer drugs.
- The observed mechanism involves apoptosis induction and cell cycle regulation.
