3D-QSAR Pharmacophore Modeling and in Silico Screening of new Bcl-xl Inhibitors

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35 Citazioni (Scopus)

Abstract

Bcl-2 proteins family members play several roles in tumoral proliferation: they inhibit proapoptotic activity during oncogenesis, support tumor cells survival, induce chemoresistance. The discovery of new small inhibitors of Bcl-xl represents a new frontier for cancer treatment. In this study, a 3D-QSAR pharmacophore model was developed, based on 42 biarylacylsulfonamides, and used to understand the structural factors affecting the inhibitory potency of these derivatives. Aromatic, negative charge, and hydrogen bond acceptor effects contribute to the inhibitory activity. The model was then employed as 3D search query to screen ZINC drug-like database in order to select new scaffolds. Finally six hits were identified. Docking study evidenced the capability of these compounds to interact with Bcl-xl receptor, and they were selected for further in vitro and in vivo assay studies.
Lingua originaleEnglish
pagine (da-a)4774-4782
Numero di pagine9
RivistaEuropean Journal of Medicinal Chemistry
Volume2010
Stato di pubblicazionePublished - 2010

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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