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New insights for the use of quercetin analogs in cancer treatment

    Domenico Iacopetta

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    ,
    Fedora Grande

    *Author for correspondence: Tel.: +39 098 449 3019; Fax: +39 098 449 3118;

    E-mail Address: fedora.grande@unical.it

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    ,
    Anna Caruso

    **Author for correspondence: Tel.: +39 098 449 3118;

    E-mail Address: anna.caruso@unical.it

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    ,
    Roberta Alessandra Mordocco

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    ,
    Maria Rosaria Plutino

    The Department of ChiBioFarAm, Institute for the Study of Nanostructured Materials, ISMN-CNR, O.U. Palermo, University of Messina, 98166, Messina, Italy

    ,
    Luca Scrivano

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    ,
    Jessica Ceramella

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    ,
    Noemi Muià

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    ,
    Carmela Saturnino

    Department of Science, University of Basilicata, 85100, Potenza, Italy

    ,
    Francesco Puoci

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    ,
    Camillo Rosano

    Ospedale Policlinico San Martino, 16132, Genoa, Italy

    &
    Maria Stefania Sinicropi

    Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy

    Published Online:https://doi.org/10.4155/fmc-2017-0118

    Aim: Quercetin (Q1) is a flavonoid widely present in plants and endowed with several pharmacological properties mostly due to its antioxidant potential. Q1 shows anticancer activity and could be useful in cancer prevention. On the other hand, Q1 is poorly soluble in water and unstable in physiological systems, and its bioavailability is very low. Methods: A small set of Q1 derivatives (Q2–Q9) has been synthesized following opportunely modified chemical procedures previously reported. Anticancer activity has been evaluated by MTT assay. Human Topoisomerases inhibition has been performed by direct enzymatic assays. Apoptosis has been evaluated by TUNEL assay. ROS production and scavenging activity have been determined by immunofluorescence. Results: The anticancer profile of a small library of Q1 analogues, in which the OH groups were all or partially replaced with hydrophobic functional groups, has been evaluated. Two of the studied compounds demonstrated an interesting cytotoxic profile in two breast cancer models showing the capability to inhibit human Topoisomerases. Conclusion: The studied compounds represent suitable leads for the development of innovative anticancer drugs.

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

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