A virtual screening approach based on a five-feature pharmacophoric model for negative modulators of GLI1 was applied to databases of commercially available compounds. The resulting quinoline derivatives showed significant ability to reduce the GLI1 protein level and were characterized by submicromolar antiproliferative activity toward human melanoma A375 and medulloblastoma DAOY cell lines. Decoration of the quinoline ring and chemical rigidification to an oxazino-quinoline scaffold allowed us to deduce SAR considerations for future ligand optimization.
Manetti, F., Maresca, L., Crivaro, E., Pepe, S., Cini, E., Singh, S., et al. (2022). Quinolines and Oxazino-quinoline Derivatives as Small Molecule GLI1 Inhibitors Identified by Virtual Screening. ACS MEDICINAL CHEMISTRY LETTERS [10.1021/acsmedchemlett.2c00249].
Quinolines and Oxazino-quinoline Derivatives as Small Molecule GLI1 Inhibitors Identified by Virtual Screening
Manetti, Fabrizio
Conceptualization
;Crivaro, EnricaMethodology
;Pepe, SaraInvestigation
;Cini, ElenaFormal Analysis
;Singh, SnigdhaMethodology
;Governa, PaoloSoftware
;Maramai, SamueleInvestigation
;Giannini, GiuseppeConceptualization
;Petricci, Elena
Supervision
2022-01-01
Abstract
A virtual screening approach based on a five-feature pharmacophoric model for negative modulators of GLI1 was applied to databases of commercially available compounds. The resulting quinoline derivatives showed significant ability to reduce the GLI1 protein level and were characterized by submicromolar antiproliferative activity toward human melanoma A375 and medulloblastoma DAOY cell lines. Decoration of the quinoline ring and chemical rigidification to an oxazino-quinoline scaffold allowed us to deduce SAR considerations for future ligand optimization.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/1213914
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