Synthesis and biological evaluation of 1H-pyrrolo[3,2-g]isoquinolines

Bioorg Med Chem. 2024 Feb 1;100:117619. doi: 10.1016/j.bmc.2024.117619. Online ahead of print.ABSTRACTA structure-activity relationship study performed on 1H-pyrrolo[3,2-g]isoquinoline scaffold identified new haspin inhibitors with nanomolar potencies and selectivity indices (SI) over 6 (inhibitory potency evaluated against 8 protein kinases). Compound 22 was the most active of the series (haspin IC50 = 76 nM). Cellular evaluation of 22 confirmed its activity for endogenous haspin in U-2 OS cells and its anti-proliferative activity against various cell lines. In addition, the binding mode of analog 22 in complex with haspin was determined by X-ray crystallography.PMID:38320389 | DOI:10.1016/j.bmc.2024.117619

Source: Bioorganic and Medicinal Chemistry - February 6, 2024 Category: Chemistry Authors: Mathilde Defois B éatrice Josselin Pierre Brindeau Andreas Kr ämer Stefan Knapp Fabrice Anizon Francis Giraud Sandrine Ruchaud Pascale Moreau Source Type: research