Synthesis, in vitro evaluation of cytotoxicity and radiosensitizer activity of novel 2-(2, 4-dinitrobenzylidene) cyclohexanone derivatives against the radioresistant HT29 cell line under aerobic condition

Introduction: Bifunctional radiosensitizer agents in which nitroaromatic moieties are attached through a linker to antineoplastic moieties have demonstrated higher cytotoxicity and radiosensitizer effects than the corresponding counterparts. This study was conducted to investigate the cytotoxicity and radiosensitizer activities of 2, 4-dinitrobenzene as a radiosensitizer moiety which connected to α, β unsaturated aryl ketones against the radioresistant human HT29 colon cancer cells. Methods: A series of bifunctional radiosensitizer derivatives that are composed of electron-affinic 2, 4-dinitrophenyl moiety and thiol reactive unsaturated conjugated ketones were prepared. The designed compounds were synthesized by the reaction of the corresponding 2, 4-dinitrobenzaldehyde, cyclohexanone and different aryl aldehydes. The cytotoxicity and radiosensitizer activity of the tested compounds were examined against HT29 colon cancer cells under aerobic condition. The IC50 value of the tested compounds and percent of survival cells were analyzed by the MTT assay. The clonogenic assay was used to assess the cell viability following treatment with the tested compounds with or without the combination of radiation. Results:This approach demonstrated that the tested compounds at the concentrations utilized have little or no cytotoxicity towards the radioresistant HT29 cell line but have great cytotoxicity and radiosensitizer activity when combined with irradiation. Conclusion: The novel bifunctional unsaturated conjugated aryl ketones which are thiol alkylators found to exhibit radiosensitivity activity. Consequently, these new developed compounds should be evaluated further to assess their potential efficacy with radiotherapy to combat malignancies in a pre-clinical animal model.

Keywords:

Glutathione , HT29 cell line , Radiosensitizer , Thiol alkylator , Unsaturated conjugated ketone