In silico screening with benzofurane- and benzopyrane-type MDR-modulators
- Author(s)
- Sascha Reibitzer, Danilo Annibali, Stephan Kopp, Monika Eder, Thierry Langer, Peter Chiba, Gerhard Ecker, Christian Noe
- Abstract
Development of inhibitors of the drug efflux pump P-glycoprotein is a versatile approach to overcome multi drug resistance (MDR) in tumor therapy. In an approach to lower the conformational flexibility of the lead compound propafenone, we synthesized a set of dihydrobenzofuranes and benzopyranones. In the case of the 4 diastereomeric dihydrobenzofuranes, no significant differences in activity regarding the configuration on the side-chains at the dihydrofurane moiety (cis or trans) was observed. This may be due to the high flexibility of the side-chains, which still allow mutually overlap of pharmacophores. The benzopyranones showed a good correlation between lipophilicity and activity with gnerally lower logpotency/log P ratios. This decrease may be due to the rigidization of the molecules. In an in silico screening approach, a set of diverse propafenone-type compounds was used to establish a pharmacophore model, which was used to screen the world drug index. Among the hits retrieved there are several compounds, which were previously described as MDR-modulators. This demonstrates the validity of the model. Œ 2003 EŽditions scientifiques et meŽdicales Elsevier SAS. All rights reserved.
- Organisation(s)
- External organisation(s)
- Universität Wien, Leopold-Franzens-Universität Innsbruck
- Journal
- Il Farmaco
- Volume
- 58
- Pages
- 185-191
- No. of pages
- 7
- ISSN
- 0014-827X
- DOI
- https://doi.org/10.1016/S0014-827X(03)00021-1
- Publication date
- 2003
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 3012 Pharmacy, Pharmacology, Toxicology
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/in-silico-screening-with-benzofurane-and-benzopyranetype-mdrmodulators(bcb973a5-7c5b-4669-9b80-87d134a5cd83).html