Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors
| Autor: | Marco A. C. Neves, M. Luisa Sá e Melo, Giorgio Colombo, Teresa C.P. Dinis |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Time Factors medicine.medical_treatment In silico Drug Evaluation Preclinical Pharmacology 01 natural sciences Steroid Structure-Activity Relationship 03 medical and health sciences Imaging Three-Dimensional Microsomes Nitriles Drug Discovery medicine Combinatorial Chemistry Techniques Humans Structure–activity relationship Aromatase 030304 developmental biology 0303 health sciences Virtual screening Molecular Structure biology Aromatase Inhibitors 010405 organic chemistry Chemistry Triazoles Ligand (biochemistry) In vitro 3. Good health 0104 chemical sciences Letrozole biology.protein Molecular Medicine Steroids Pharmacophore |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm800945c |
| Popis: | Suppression of estrogen biosynthesis by aromatase inhibition is an effective approach for the treatment of hormone sensitive breast cancer. Third generation non-steroid aromatase inhibitors have shown important benefits in recent clinical trials with postmenopausal women. In this study we have developed a new ligand-based strategy combining important pharmacophoric and structural features according to the postulated aromatase binding mode, useful for the virtual screening of new potent non-steroid inhibitors. A small subset of promising drug candidates was identified from the large NCI database, and their antiaromatase activity was assessed on an in vitro biochemical assay with aromatase extracted from human term placenta. New potent aromatase inhibitors were discovered to be active in the low nanomolar range, and a common binding mode was proposed. These results confirm the potential of our methodology for a fast in silico high-throughput screening of potent non-steroid aromatase inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|