@article{pmid36990245,

title = {Synthesis and Biological Evaluation of DIDS Analogues as Efficient Inhibitors of RAD51 Involved in Homologous Recombination},

author = {Alexandre Demeyer and Lucie Fonteneau and Marion Liennard and Claire Foyer and Pierre Weigel and Adèle Laurent and Jacques Lebreton and Fabrice Fleury and Monique Mathé-Allainmat},

url = {hal-04234850v1 },

doi = {10.1016/j.bmcl.2023.129261},

issn = {1464-3405},

year  = {2023},

date = {2023-03-01},

urldate = {2023-03-01},

journal = {Bioorg Med Chem Lett},

pages = {129261},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{demeyer_inhibiting_2021,

title = {Inhibiting homologous recombination by targeting RAD51 protein},

author = {Alexandre Demeyer and Houda Benhelli-Mokrani and B. Chénais and Pierre Weigel and Fabrice Fleury},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0304419X21000949},

doi = {10.1016/j.bbcan.2021.188597},

issn = {0304419X},

year  = {2021},

date = {2021-09-15},

urldate = {2021-09-15},

journal = {Biochimica et Biophysica Acta (BBA) - Reviews on Cancer},

volume = {1876},

number = {2},

pages = {188597},

abstract = {Homologous recombination (HR) is involved in repairing DNA double-strand breaks (DSB), the most harmful for the cell. Regulating HR is essential for maintaining genomic stability. In many forms of cancer, overactivation of HR increases tumor resistance to DNA-damaging treatments. RAD51, HR's core protein, is very often overexpressed in these cancers and plays a critical role in cancer cell development and survival. Targeting RAD51 directly to reduce its activity and its expression is therefore one strategy to sensitize and overcome resistance cancer cells to existing DNA-damaging therapies which remains the limiting factor for the success of targeted therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{velic_molecular_2021,

title = {Molecular Determinant of DIDS Analogs Targeting RAD51 Activity},

author = {Denis Velic and Alexandre Demeyer and Thibaut Peterlini and Houda Benhelli-Mokrani and Monique Mathé-Allainmat and Jean-Yves Masson and Fabrice Fleury},

url = {https://www.mdpi.com/1420-3049/26/18/5460},

doi = {10.3390/molecules26185460},

issn = {1420-3049},

year  = {2021},

date = {2021-09-15},

urldate = {2021-09-15},

journal = {Molecules},

volume = {26},

number = {18},

pages = {5460},

abstract = {RAD51 is the central protein in DNA repair by homologous recombination (HR), involved in several steps of this process. It is shown that overexpression of the RAD51 protein is correlated with increased survival of cancer cells to cancer treatments. For the past decade, RAD51 overexpression-mediated resistance has justified the development of targeted inhibitors. One of the first molecules described to inhibit RAD51 was the 4,4 -diisothiocyanato-stilbene-2,2 -disulfonic acid (DIDS) molecule. This small molecule is effective in inhibiting different functions of RAD51, however its mode of action and the chemical functions involved in this inhibition have not been identified. In this work, we used several commercial molecules derived from DIDS to characterize the structural determinants involved in modulating the activity of RAD51. By combining biochemical and biophysical approaches, we have shown that DIDS and two analogs were able to inhibit the binding of RAD51 to ssDNA and prevent the formation of D-loop by RAD51. Both isothiocyanate substituents of DIDS appear to be essential in the inhibition of RAD51. These results open the way to the synthesis of new molecules derived from DIDS that should be greater modulators of RAD51 and more efficient for HR inhibition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}