Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Predicting Novel Antitumor Agents: 3D-Pharmacophore Mapping of beta-N-biaryl Ether Sulfonamide-Based Hydroxamates as Potentially MMP-2 Inhibitors

Full text
Author(s):
Turra, Kely Medeiros [1] ; Rivelli, Diogo Pineda [1] ; de Moraes Barros, Silvia Berlanga [1] ; Mesquita Pasqualoto, Kerly Fernanda [2]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Lab Cytopathol, Dept Clin Chem & Toxicol, Fac Pharmaceut Sci, BR-05508000 Sao Paulo - Brazil
[2] Butantan Inst, Biochem & Biophys Lab, BR-05503900 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: MOLECULAR INFORMATICS; v. 33, n. 9, p. 573-587, SEP 2014.
Web of Science Citations: 2
Abstract

Matrix metalloproteinases (MMP) are a group of enzymes related to extracelular matrix remodeling. Some types of MMP are overexpressed by malignant tumors, mainly the MMP-2 subtype, and have been associated to cancer invasiveness and metastasis. A receptor-independent (RI) 4D-QSAR formalism was applied, herein, to a set of forty beta-N-biaryl ether sulfonamide hydroxamates, previously reported as potent MMP-2 inhibitors, in order to map 3D-pharmacophore models and predict novel antitumor agents. The best RI 4D-QSAR model was statistically significant (N= 30, r(2) = 0.93, q(2) = 0.88, five occupancy descriptors (GCOD), LSE= 0.04, LOF= 0.11, outliers= 0), robust and not obtained by chance. The external predictability was 75% (test set; N= 8). A different orientation (binding mode) in the MMP-2 catalytic site was suggested regarding the most hydrophobic portion (R-1) of the compounds' structure. Compounds were predicted and their inhibitory activity against MMP-2 was calculated by using the optimum RI 4D-QSAR model. The findings have provided interesting information to drive the designing and synthesis of novel potentially MMP-2 inhibitors against melanoma invasion. (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