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  3. New rhodol-sulforaphane conjugates as innovative isothiocyanate-based cytotoxic agents for cancer cells

New rhodol-sulforaphane conjugates as innovative isothiocyanate-based cytotoxic agents for cancer cells

  • Eur J Med Chem. 2024 Oct 3:280:116936. doi: 10.1016/j.ejmech.2024.116936.
Andrea Milelli 1,  Elena Catanzaro 2,  Giulia Greco 3,  Cinzia Calcabrini 1,  Eleonora Turrini 1,  Francesca Maffei 1,  Sabrina Burattini 4,  Melissa Guardigni 1,  Claudia Sissi 5,  Michael Schnekenburger 6,  Marc Diederich 7,  Piero Sestili 8,  Carmela Fimognari 9
Affiliations

Affiliations

  • 1 Department for Life Quality Studies, University of Bologna, Corso D'Augusto 237, 47921, Rimini, Italy.
  • 2 Cell Death Investigation and Therapy (CDIT) Laboratory, Department of Human Structure and Repair, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium; Cancer Research Institute Ghent, Ghent, Belgium.
  • 3 Department of Chemistry "Giacomo Ciamician", University of Bologna, Via Selmi 2, 40126, Bologna, Italy.
  • 4 Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Ca' Le Suore, 2/4, 61029, Urbino, Italy.
  • 5 Department of Pharmaceutical and Pharmacological Science, University of Padova, Via Marzolo 5, 35131, Padua, Italy.
  • 6 Laboratoire de Biologie Moléculaire et Cellulaire Du Cancer (LBMCC), BAM3 Pavillon 2, 6A Rue Nicolas-Ernest Barblé, L-1210, Luxembourg, Luxembourg.
  • 7 Research Institute of Pharmaceutical Sciences & Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
  • 8 Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Ca' Le Suore, 2/4, 61029, Urbino, Italy. Electronic address: piero.sestili@uniurb.it.
  • 9 Department for Life Quality Studies, University of Bologna, Corso D'Augusto 237, 47921, Rimini, Italy. Electronic address: carmela.fimognari@unibo.it.
PMID: 39395301 DOI: 10.1016/j.ejmech.2024.116936
Abstract

In search of semisynthetic derivatives with increased antitumor activity, we condensed sulforaphane (SFR) with rhodol, a fluorophore platform capable of modifying the intracellular trafficking and pharmacokinetics of the linked molecules. The two tested derivatives, namely MG28 and MG46, showed a far higher, as compared to SFR, cytotoxicity toward Cancer cells. Apoptotic cell death was preceded by the extensive generation of DNA lesions, which were repaired relatively slowly and caused formation of micronuclei. Unlike SFR, rhodol-SFR conjugates' DNA lesions resulted from direct interactions with nuclear DNA. Overall, MG28 and MG46 exhibit a remarkable cytotoxic effect, which is the likely consequence of their direct and intense DNA damaging activity, i.e., a novel and peculiar mechanism arising from the conjugation of the parental rhodol and SFR. Considering that a wide number of clinically used drugs kill Cancer cells by inducing DNA damage, MG could represent a new and promising chance in antitumor chemotherapy.

Keywords

Anticancer agents; Cytotoxicity; DNA damage; Isothiocyanates; Rhodol; Sulforaphane.

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