Related Experiment Video
Updated: Jan 5, 2026
Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Antiproliferative and genotoxic potential of xanthen-3-one derivatives
Elma Veljović1, Selma Špirtović-Halilović1, Samija Muratović1
1University of Sarajevo, Faculty of Pharmacy, 71000Sarajevo, Bosnia and Herzegovina.
Abstract:
Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4' position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L-1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L-1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L-1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.
Insights
Novel xanthen-3-one derivatives show potent antiproliferative activity against various cancer cell lines. A trifluormethyl-substituted compound demonstrated significant inhibition with no observed genotoxic or cytotoxic effects, supported by molecular docking studies.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Cancer Biology
Background:
- Xanthen-3-one derivatives are a class of compounds with known biological activities.
- Exploring novel derivatives for enhanced therapeutic potential is crucial in cancer research.
Purpose of the Study:
- To evaluate the in vitro antiproliferative activity of twelve synthesized 2,6,7-trihydroxyxanthen-3-one derivatives.
- To identify specific structural features correlating with potent anticancer effects.
- To assess the safety profile (cytotoxicity and genotoxicity) of promising candidates.
Main Methods:
- In vitro screening of compounds against HeLa, SW620, HepG2, and A549 tumor cell lines.
- Determination of half-maximal inhibitory concentration (IC50) values.
- Cytotoxicity and genotoxicity assessment using the cytokinesis-block micronucleus cytome assay.
- Molecular docking simulations to analyze target binding interactions.
Main Results:
- A derivative with a trifluormethyl group at the C-4' position exhibited strong inhibition against HeLa (IC50: 0.7 µmol L-1) and A549 (IC50: 4.1 µmol L-1) cells.
- Compounds with chlorine and fluorine substituents showed significant activity against SW620 (IC50: 4.1 µmol L-1) and HepG2 (IC50: 4.2 µmol L-1) cells.
- The trifluormethyl derivative displayed no genotoxic or cytotoxic effects in human lymphocyte cultures.
- Molecular docking revealed important hydrogen bond interactions between potent compounds and molecular targets.
Conclusions:
- Specific 2,6,7-trihydroxyxanthen-3-one derivatives possess significant antiproliferative potential against multiple cancer types.
- The trifluormethyl derivative is a promising candidate for further anticancer drug development due to its efficacy and favorable safety profile.
- Structure-activity relationships and target interactions provide insights for designing more potent anticancer agents.
