Protease inhibitors: synthesis of matrix metalloproteinase and bacterial collagenase inhibitors incorporating 5-amino-2-mercapto-1,3,4-thiadiazole zinc binding functions.
Matrix metalloproteinase (MMP)/bacterial collagenase inhibitors incorporating 5-amino-2-mercapto-1,3,4-thiadiazole zinc binding functions are reported. A series of compounds was prepared by reaction of arylsulfonyl isocyanates or arylsulfonyl halides with phenylalanyl-alanine, followed by coupling with 5-amino-2-mercapto-1,3,4-thiadiazole in the presence of carbodiimides. These new compounds were assayed as inhibitors of human MMP-1, MMP-2, MMP-8 and MMP-9, and of the collagenase isolated from the anaerobe Clostridium histolyticum (ChC). The new derivatives proved to be powerful inhibitors of these metalloproteases, with activities in the low micromolar range for some of the target enzymes, depending on the substitution pattern at the arylsulfonyl(ureido) moieties.
Scozzafava
Andrea
A
Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Sesto Fiorentino, Florence, Italy.
Supuran
Claudiu T
CT
D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D013830:Thiadiazoles / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
C102557:2-mercapto-5-phenylamino-1,3,4-thiadiazole; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013830:Thiadiazoles; D020782:Matrix Metalloproteinases; D003012:Microbial Collagenase; D015032:Zinc