Rossello Armando, Nuti Elisa, Orlandini Elisabetta, Carelli Paolo, Rapposelli Simona, Macchia Marco, Minutolo Filippo, Carbonaro Laura, Albini Adriana, Benelli Roberto, Cercignani Giovanni, Murphy Gillian, Balsamo Aldo
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
Bioorg Med Chem. 2004 May 1;12(9):2441-50. doi: 10.1016/j.bmc.2004.01.047.
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).
设计合成了8型和10型新型N-芳基磺酰基取代的烷氧基氨基乙酰氧肟酸衍生物，它们是已知2型和7型磺酰胺基基质金属蛋白酶抑制剂（MMPi）的氧类似物，并测试了它们对某些基质金属蛋白酶的抑制活性。在新的磺酰胺10中获得的基于磺酰胺的MMPi的药效团中心骨架中，联苯磺酰胺基团与氧氨基氧的组合似乎能够赋予对MMP-2相对于MMP-1的选择性。这种类型中最有效的衍生物10a，在对纤维肉瘤HT1080细胞系（过表达MMP-2和MMP-9的肿瘤细胞）进行的基质胶侵袭体外模型中，显示出与类似物参考药物CGS27023A（2）相似的抗侵袭特性。
