A novel set of ss-N-biaryl ether sulfonamide hydroxamates as potential MMPs inhibitors: Molecular dynamics simulations and molecular properties evaluation

Author(s)

Turra, Kely Medeiros ; Mesquita Pasqualoto, Kerly Fernanda ; de Moraes Barros, Silvia Berlanga

• Document type: Journal article
• Source: International Journal of Quantum Chemistry; v. 112, n. 20, p. 16-pg., 2012-10-15.

Abstract

Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases involved in the extracellular matrix degradation. MMP-2 and MMP9 are overexpressed in several human cancer types, including melanoma, thus the development of new compounds to inhibit MMPs' activity is desirable. Molecular dynamic simulation and molecular properties calculations were performed on a set of novel beta-N-biaryl ether sulfonamide-based hydroxamates, reported as MMP-2 and MMP-9 inhibitors, for providing data to develop an exploratory analysis. Thermodynamic, electronic, and steric descriptors have significantly discriminated highly active from moderately and less active inhibitors of MMP-2 whereas apparent partition coefficient at pH 1.5 was also significant for the MMP-9 data set. Compound 47 was considered an outlier in all analysis, indicating the presence of a bulky substituent group in R3 is crucial to this set of inhibitors for the establishment of molecular interactions with the S1 subsite of both enzymes, but there is a limit. (C) 2012 Wiley Periodicals, Inc. (AU)

• FAPESP's process: 10/19142-1 - Molecular modeling methods and Computer-Aided Molecular Design Formalism for elucidating the mechanism of action of matrix metalloproteinases inhibitors.
• Grantee: Kely Medeiros Turra
• Support Opportunities: Scholarships in Brazil - Doctorate