New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2)

  • Bioorg Med Chem. 2004 May 1;12(9):2441-50. doi: 10.1016/j.bmc.2004.01.047.
Armando Rossello  1 ,  Elisa Nuti ,  Elisabetta Orlandini ,  Paolo Carelli ,  Simona Rapposelli ,  Marco Macchia ,  Filippo Minutolo ,  Laura Carbonaro ,  Adriana Albini ,  Roberto Benelli ,  Giovanni Cercignani ,  Gillian Murphy ,  Aldo Balsamo
Affiliations
  • 1. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Pisa, Via Bonanno, 6, 56126 Pisa, Italy. [email protected]
PMID: 15080939 DOI: 10.1016/j.bmc.2004.01.047
Abstract

New N-arylsulfonyl-substituted alkoxyaminoaceto hydroxamic acid derivatives of types 8 and 10 designed as oxa-analogues of known sulfonamide-based MMPi of types 2 and 7 were synthesized and tested for their inhibitory activities on some Matrix Metalloproteinases. The combination of a biphenylsulfonamide group with oxyamino oxygen in the pharmacophoric central skeleton of sulfonamide-based MMPi obtained in the new sulfonamides 10 seems to be able to give selectivity for MMP-2 over MMP-1. The most potent derivative of this type, 10a, shows similar anti-invasive properties to the analogue reference drug CGS27023A, 2, in an in vitro model of invasion on matrigel, carried out on cellular lines of fibrosarcoma HT1080 (tumoural cells over-expressing MMP-2 and MMP-9).

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