Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with improved selectivity.

Date publication

septembre 2008

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BOURGUET Erika , Pr GUILLAUME Dominique , Pr SAPI Janos

Tous les auteurs :
Ledour G, Moroy G, Rouffet M, Bourguet E, Guillaume D, Decarme M, Elmourabit H, Auge F, Alix AJ, Laronze JY, Bellon G, Hornebeck W, Sapi J

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/18782669

Résumé

Hydrazide derivatives of Ilomastat, carrying either aryl groups or distinct alkyl and arylsulfonyl moieties were synthesized and evaluated for their MMP inhibitory activity. Potent and selective MMP-9 inhibition (IC(50)=3 nM) was observed for compound 3m (arylsulfonyl group: 4-(4-Br-C6H4)-C6H4-SO(2)-). Interaction with the S2 enzyme subsite is mainly responsible for the inhibitory properties of this derivative as confirmed by molecular docking computation.

Référence

Bioorg Med Chem. 2008 Sep 15;16(18):8745-59