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Development and in vivo evaluation of fused benzazole analogs of anti-melanoma agent HA15

    Antoine Millet‡

    Institut de Chimie de Nice CRNS UMR7272, Université Côte d’Azur, 28 Avenue Valrose, Nice, 06108, France

    ‡Authors contributed equally

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    ,
    Mauro Safir Filho‡

    Institut de Chimie de Nice CRNS UMR7272, Université Côte d’Azur, 28 Avenue Valrose, Nice, 06108, France

    ‡Authors contributed equally

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    ,
    Nedra Hamouda-Tekaya‡

    Centre Méditerranéen de Médecine Moléculaire (C3M), INSERM, U1065, Team 12, Université Côte d’Azur, 151 Route de Saint-Antoine de Ginestière, Nice, 06200, France

    ‡Authors contributed equally

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    Elisa Cavazza

    Centre Méditerranéen de Médecine Moléculaire (C3M), INSERM, U1065, Team 12, Université Côte d’Azur, 151 Route de Saint-Antoine de Ginestière, Nice, 06200, France

    ,
    Patricia Abbe

    Centre Méditerranéen de Médecine Moléculaire (C3M), INSERM, U1065, Team 12, Université Côte d’Azur, 151 Route de Saint-Antoine de Ginestière, Nice, 06200, France

    ,
    Johanna Rüdiger

    Institut de Chimie de Nice CRNS UMR7272, Université Côte d’Azur, 28 Avenue Valrose, Nice, 06108, France

    ,
    Magali Plaisant

    Centre Méditerranéen de Médecine Moléculaire (C3M), INSERM, U1065, Team 12, Université Côte d’Azur, 151 Route de Saint-Antoine de Ginestière, Nice, 06200, France

    ,
    Julie Mayen

    Institut de Chimie de Nice CRNS UMR7272, Université Côte d’Azur, 28 Avenue Valrose, Nice, 06108, France

    ,
    Stéphane Rocchi

    **Author for correspondence:

    E-mail Address: stephane.rocchi@univ-cotedazur.fr

    Centre Méditerranéen de Médecine Moléculaire (C3M), INSERM, U1065, Team 12, Université Côte d’Azur, 151 Route de Saint-Antoine de Ginestière, Nice, 06200, France

    ,
    Cyril Ronco

    *Author for correspondence:

    E-mail Address: cyril.ronco@univ-cotedazur.fr

    Institut de Chimie de Nice CRNS UMR7272, Université Côte d’Azur, 28 Avenue Valrose, Nice, 06108, France

    &
    Rachid Benhida

    ***Author for correspondence:

    E-mail Address: rachid.benhida@univ-cotedazur.fr

    Institut de Chimie de Nice CRNS UMR7272, Université Côte d’Azur, 28 Avenue Valrose, Nice, 06108, France

    Mohamed VI Polytechnic University, UM6P, Department of Chemical and Biochemical Sciences, Green ProcessEngineering, CBS, Ben Guerir, 43150, Morocco

    Published Online:https://doi.org/10.4155/fmc-2021-0001

    Background: In line with our recent discovery of an efficient anticancer thiazolebenzenesulfonamide framework HA15 (1) based on a remarkable endoplasmic reticulum stress inducement mode of action, we report herein a series of innovative constrained HA15 analogs, featuring four types of bicylic derivatives. Results: The structure–activity relationship analysis, using a cell line assay, led us to identify a novel version of HA15: a new benzothiazole derivative (10b) exhibiting important anti-melanoma effect against sensitive and resistant melanoma cells. Meanwhile, compound 10b induced a significant tumor growth inhibition in vivo with no apparent signs of toxicity. Conclusion: These results consistently open new directions to improve and develop more powerful anticancer therapeutics harboring this type of fused framework.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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