New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2)
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- 作者：Rossello ; Armando ; Nuti ; Elisa ; Orlandini ; Elisabetta ; Carelli ; Paolo ; Rapposelli ; Simona ; et. al.
- 关键词：Gelatinase A inhibitors ; MMP-2 selective ; Sulfonamide-based MMP inhibitors
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2004
- 出版时间：May 1, 2004
- 年：2004
- 卷：12
- 期：9
- 页码：2441-2450
- 全文大小：415 K
文摘
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).