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Quinolines and Oxazino-quinoline Derivatives as Small Molecule GLI1 Inhibitors Identified by Virtual Screening.

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.

SUBMITTER: Manetti F

PROVIDER: S-EPMC9377010 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Quinolines and Oxazino-quinoline Derivatives as Small Molecule GLI1 Inhibitors Identified by Virtual Screening.

Manetti Fabrizio F Maresca Luisa L Crivaro Enrica E Pepe Sara S Cini Elena E Singh Snigdha S Governa Paolo P Maramai Samuele S Giannini Giuseppe G Stecca Barbara B Petricci Elena E

ACS medicinal chemistry letters 20220722 8

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 ...[more]

PMID: 35978701

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