Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors.
A series of bis-(arylsulfonamide) hydroxamate inhibitors were synthesized. These compounds exhibit good potency against MMP-7 and MMP-9 depending on the nature, steric bulk, and substitution pattern of the substituents in the benzene ring. In general, the preliminary structure-activity relationships (SAR) suggest that among the DAPA hydroxamates (i) electron-rich benzene rings of the sulfonamides may produce better inhibitors than electron-poor analogs. However, potential H-bond acceptors can reverse the trend depending on the isozyme; (ii) isozyme selectivity between MMP-7 and -9 can be conferred through steric bulk and substitution pattern of the substituents in the benzene ring, and (iii) the MMP-10 inhibition pattern of the compounds paralleled that for MMP-9.
Subramaniam
Rajesh
R
Department of Pharmaceutical Sciences, North Dakota State University, 1401 Albrecht Blvd, Fargo, ND 58105, USA.
Haldar
Manas K
MK
Tobwala
Shakila
S
Ganguly
Bratati
B
Srivastava
D K
DK
Mallik
Sanku
S
D015195:Drug Design; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D013449:Sulfonamides