| Title: |
Structure-based selectivity optimization of piperidine-pteridine derivatives as potent leishmania pteridine reductase inhibitors. |
| Authors: |
Corona P.; Gibellini F.; Saxena P.; Carta A.; Loriga M.; Luciani R.; Paglietti G.; Guerrieri D.; Nerini E.; Gupta S.; Hannaert V.; Michels P. A.; Ferrari S.; Costi P. M.; CAVALLI, ANDREA |
| Contributors: |
Corona P.; Gibellini F.; Cavalli A.; Saxena P.; Carta A.; Loriga M.; Luciani R.; Paglietti G.; Guerrieri D.; Nerini E.; Gupta S.; Hannaert V.; Michels P.A.; Ferrari S.; Costi P.M. |
| Publication Year: |
2012 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
DRUG DISCOVERY; PARASITIC DISEASES; MOLECULAR MODELING |
| Description: |
The upregulation of pteridine reductase (PTR1) is a major contributor to antifolate drug resistance in Leishmania spp., as it provides a salvage pathway that bypasses dihydrofolate reductase (DHFR) inhibition. The structure-based optimization of the PTR1 inhibitor methyl-1-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]- piperidine-4-carboxylate (1) led to the synthesis of a focused compound library which showed significantly improved selectivity for the parasite’s folate-dependent enzyme. When used in combination with pyrimethamine, a DHFR inhibitor, a synergistic effect was observed for compound 5b. This work represents a step forward in the identification of effective antileishmania agents. |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/wos/WOS:000309643500011; volume:55; firstpage:8318; lastpage:8329; numberofpages:12; journal:JOURNAL OF MEDICINAL CHEMISTRY; http://hdl.handle.net/11585/128687 |
| DOI: |
10.1021/jm300563f |
| Availability: |
http://hdl.handle.net/11585/128687; https://doi.org/10.1021/jm300563f |
| Accession Number: |
edsbas.9B1F679F |
| Database: |
BASE |