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Keto-bridged dual triazole-linked benzenesulfonamides as potent carbonic anhydrase and cathepsin B inhibitors

    Lalit Vats

    Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India

    Department of Chemistry, Government College Bherian, Pehowa, Kurukshetra, Haryana, 136128, India

    ,
    Priyanka Arya

    Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India

    ,
    Rajiv Kumar

    Ch. Mani Ram Godara Government College for Women, Bhodia Khera, Fatehabad, Haryana, 125050, India

    ,
    Simone Giovannuzzi

    Neurofarba Department, Pharmaceutical & Nutraceutical Section, University of Florence, Florence, Italy

    ,
    Neera Raghav

    Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India

    ,
    Claudiu T Supuran

    Neurofarba Department, Pharmaceutical & Nutraceutical Section, University of Florence, Florence, Italy

    &
    Pawan K Sharma

    *Author for correspondence: Tel.: +91 941 645 7355;

    E-mail Address: talk2pawan@cuh.ac.in

    Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India

    Department of Chemistry, Central University of Haryana, Mahendergarh, 123031, India

    Published Online:https://doi.org/10.4155/fmc-2023-0201

    Background: Inhibition of human carbonic anhydrase (hCA) isoforms IX and XII with concurrent inhibition of cathepsin B is a promising approach for targeting cancers. Methods/results: 28 keto-bridged dual triazole-containing benzenesulfonamides were synthesized and tested, following the multitarget approach, for their efficacy as inhibitors of cathepsin B and hCA isoforms (I, II, IX, XII). The synthesized compounds showed excellent inhibition of CA isoforms (IX and XII) and cathepsin B. Compound 8i exhibited better and more selective inhibition of the cancer-associated isoform hCA IX as compared with acetazolamide (reference drug) and SLC-0111 (potent lead as carbonic anhydrase inhibitor). Molecular docking studies were also carried out. Conclusion: The present work gives important generalizations for the development of isoform-selective hCA inhibitors endowed with anti-cathepsin properties.

    Graphical abstract

    A small library of 28 novel benzenesulfonamides containing a keto-bridged dual triazolic moiety were synthesized and assayed for their anti-cancer potential in terms of anti-carbonic anhydrase and anti-cathepsin B inhibition potential.

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

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