Structure and Ligand-based Design of P-glycoprotein Inhibitors: A Historical Perspective

• Type: Another Publication in an International Scientific Journal
• Date: 2012

Authors

Andreia Palmeira (Author) Other; Emilia Sousa (Author) FFUP; Helena Vasconcelos, MH (Author) FFUP; Madalena Pinto (Author) FFUP; Miguel X Fernandes (Author) Other

Journal

Title: Current Pharmaceutical Design

Vol. 18

Pages: 4197-4214

ISSN: 1381-6128

Publisher: Bentham Science

Indexing

ISI Proceedings

ISI Web of Knowledge - 38 Citations

Scopus - 39 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-6K2

DOI: 10.2174/138161212802430530

Abstract (EN): Computer-assisted drug design (CADD) is a valuable approach for the discovery of new chemical entities in the field of cancer therapy. There is a pressing need to design and develop new, selective, and safe drugs for the treatment of multidrug resistance (MDR) cancer forms, specifically active against P-glycoprotein (P-gp). Recently, a crystallographic structure for mouse P-gp was obtained. However, for decades the design of new P-gp inhibitors employed mainly ligand-based approaches (SAR, QSAR, 3D-QSAR and pharmacophore studies), and structure-based studies used P-gp homology models. However, some of those results are still the pillars used as a starting point for the design of potential P-gp inhibitors. Here, pharmacophore mapping, (Q) SAR, 3D-QSAR and homology modeling, for the discovery of P-gp inhibitors are reviewed. The importance of these methods for understanding mechanisms of drug resistance at a molecular level, and design P-gp inhibitors drug candidates are discussed. The examples mentioned in the review could provide insights into the wide range of possibilities of using CADD methodologies for the discovery of efficient P-gp inhibitors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 18