Synthesis and Antiproliferative Activity of Acetamidoquinoline Derivatives for Melanoma

Abstract

The RAF-MEK-ERK MAP kinase cascade appears to be intimately involved in the regulation of cell cycle progression and apoptosis. Disruption of this signaling cascade could thus offer a novel approach for cancer chemotherapy. Activating mutations in B-Raf, one of the Raf family members, are reported to be present in 66% of malignant malanoma. Melanoma is a serious and sometimes lifethreatening cancer. To develop b-Raf serine/threonine kinase inhibitors for the treatment of malignant melanoma, a series of acetamidoquinoline derivatives with novel hinge moiety were designed and synthesized. As a result of cell-based assay against A375 human melanoma cell line, several compounds exhibited superior antiproliferative activities to Sorafenib as a refernce compound.