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Enhanced Efficacy of Gefitinib in Drug‐Sensitive and Drug‐Resistant Cancer Cell Lines after Arming with a Singlet Oxygen Releasing Moiety
Ist Teil von
ChemMedChem, 2020-05, Vol.15 (9), p.794-798
Ort / Verlag
Germany: Wiley Subscription Services, Inc
Erscheinungsjahr
2020
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Attractive results have been achieved with small‐molecule target‐based drugs in the anticancer field; however, enhancing their treatment effect and solving the problem of drug resistance remain key concerns worldwide. Inspired by the specific affinity of gefitinib for tumour cells and the strong oxidation capacity of singlet oxygen, we combined a chemically generated singlet oxygen moiety with the small‐molecule targeted drug gefitinib to improve its anticancer effect. We designed and synthesised a novel compound (Y5‐1), in which a small‐molecule targeted therapy agent (gefitinib) and a singlet oxygen (provided by an in vitro photodynamic reaction) thermally controlled releasing moiety are covalently conjugated. We demonstrated that the introduction of the singlet oxygen thermally controlled releasing moiety enhanced the anticancer activities of gefitinib. The results of this study are expected to provide a novel strategy to enhance the effect of chemotherapy drugs on drug‐resistant cell lines.
The oxygen of death: We have introduced a chemically generated singlet oxygen moiety into gefitinib, which can inhibit the activity of tyrosine kinase. The 1O2 thermally controlled releasing moiety enhances the anticancer activities of gefitinib on drug‐resistant cell lines by increasing the intracellular 1O2 level.