JMJD3 is a member of the KDM6 subfamily and catalyses the demethylation of lysine 27 on histone H3 (H3K27). This protein was identified as useful tool in understanding the role of epigenetics in inflammatory conditions and in cancer as well. Guided by a virtual fragment screening approach, we identified the benzoxazole scaffold as a new hit suitable for the development of tighter JMJD3 inhibitors. Compounds were synthesized by a microwave assisted one pot reaction under catalyst and solvent-free conditions. Among these, compound 8 presented the highest inhibitory activity (IC50 = 1.22 ± 0.22 ?M) in accordance with molecular modeling calculations. Moreover, 8 induced the cycle arrest in S-phase on A375 melanoma cells.
Identification of the 2-benzoxazol-2-yl-phenol scaffold as new hit for JMJD3 inhibition
Assunta Giordano;
2019
Abstract
JMJD3 is a member of the KDM6 subfamily and catalyses the demethylation of lysine 27 on histone H3 (H3K27). This protein was identified as useful tool in understanding the role of epigenetics in inflammatory conditions and in cancer as well. Guided by a virtual fragment screening approach, we identified the benzoxazole scaffold as a new hit suitable for the development of tighter JMJD3 inhibitors. Compounds were synthesized by a microwave assisted one pot reaction under catalyst and solvent-free conditions. Among these, compound 8 presented the highest inhibitory activity (IC50 = 1.22 ± 0.22 ?M) in accordance with molecular modeling calculations. Moreover, 8 induced the cycle arrest in S-phase on A375 melanoma cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
