Synthesis of Novel Diaziridinyl Quinone Isoxazole Hybrids and Evaluation of Their Anti-Cancer Activity as Potential Tubulin-Targeting Agents

Abstract

Two series of diaziridinyl quinone isoxazole derivatives were prepared and evaluated for their cytotoxic activity against MCF7, HeLa, BT549, A549 and HEK293 cell lines and interaction with tubulin. Compounds (6a–m ) showed promising activity against all the 5 human cancer cell lines. Compounds 6a, 6e and 6 m were potent [IC₅₀ ranging between 2.21 µg to 2.87 µg] on ER-positive MCF7 cell line similar to the commercially available drug molecule Doxorubicin. The results from docking models are in consistent with the experimental values which demonstrated the favourable binding modes of compounds 6a–m to the interface of α- and β-tubulin dimer.

Key words

isoxazole - quinone - aziridine - diaziridinyl quinone isoxazole - cytotoxicity - molecular docking

• References

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