Synthesis and biological evaluation of DIDS analogues as efficient inhibitors of RAD51 involved in homologous recombination.

Autor: Demeyer A; Nantes Université, CNRS, US2B, UMR 6286, DNA-repair Group, F-44000 Nantes, France., Fonteneau L; Nantes Université, CNRS, US2B, UMR 6286, DNA-repair Group, F-44000 Nantes, France., Liennard M; Nantes Université, CNRS, US2B, UMR 6286, DNA-repair Group, F-44000 Nantes, France; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Foyer C; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Weigel P; Nantes Université, CNRS, US2B, UMR 6286, DNA-repair Group, F-44000 Nantes, France., Laurent AD; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Lebreton J; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France., Fleury F; Nantes Université, CNRS, US2B, UMR 6286, DNA-repair Group, F-44000 Nantes, France. Electronic address: fabrice.fleury@univ-nantes.fr., Mathé-Allainmat M; Nantes Université, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France. Electronic address: monique.mathe@univ-nantes.fr.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2023 May 01; Vol. 87, pp. 129261. Date of Electronic Publication: 2023 Mar 28.
DOI: 10.1016/j.bmcl.2023.129261
Abstrakt: RAD51 is a pivotal protein of the homologous recombination DNA repair pathway, and is overexpressed in some cancer cells, disrupting then the efficiency of cancer-treatments. The development of RAD51 inhibitors appears as a promising solution to restore these cancer cells sensitization to radio- or chemotherapy. From a small molecule identified as a modulator of RAD51, the 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), two series of analogues with small or bulky substituents on the aromatic parts of the stilbene moiety were prepared for a structure-activity relationship study. Three compounds, the cyano analogue (12), and benzamide (23) or phenylcarbamate (29) analogues of DIDS were characterized as novel potent RAD51 inhibitors with HR inhibition in the micromolar range.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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