New imidazoquinoxaline derivatives: Synthesis, biological evaluation on melanoma, effect on tubulin polymerization and structure–activity relationships

Abstract : Microtubules are considered as important targets of anticancer therapy. EAPB0503 and its structural imidazo[1,2-a]quinoxaline derivatives are major microtubule-interfering agents with potent anticancer activity. In this study, the synthesis of several new derivatives of EAPB0503 is described, and the anticancer efficacy of 13 novel derivatives on A375 human melanoma cell line is reported. All new compounds show significant antiproliferative activity with IC50 in the range of 0.077-122μM against human melanoma cell line (A375). Direct inhibition of tubulin polymerization assay in vitro is also assessed. Results show that compounds 6b, 6e, 6g, and EAPB0503 highly inhibit tubulin polymerization with percentages of inhibition of 99%, 98%, 90%, and 84% respectively. Structure-activity relationship studies within the series are also discussed in line with molecular docking studies into the colchicine-binding site of tubulin.
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https://hal.umontpellier.fr/hal-02299123
Contributeur : Anthony Herrada <>
Soumis le : vendredi 27 septembre 2019 - 14:57:01
Dernière modification le : mercredi 13 novembre 2019 - 11:50:04

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Zahraa Zghaib, Jean-François Guichou, Johanna Vappiani, Nicole Bec, Kamel Hadj-Kaddour, et al.. New imidazoquinoxaline derivatives: Synthesis, biological evaluation on melanoma, effect on tubulin polymerization and structure–activity relationships. Bioorganic and Medicinal Chemistry, Elsevier, 2016, 24 (11), pp.2433-2440. ⟨10.1016/j.bmc.2016.04.004⟩. ⟨hal-02299123⟩

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