Synthesis of retinoid enhancers based on 2-aminobenzothiazoles for anti-cancer therapy.

Indole-3-amides and dipeptides were produced from 2-aminobenzothiazoles using the PyBop peptide coupling reagent. These analogues were tested in anti-cancer cell viability assays against SH-SY5Y neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines, and were found to exhibit cytotoxic activities at concentrations ranging from 0.1 to 20μM. These compounds were also found to act additively with a low dosage of 13-cis-retinoic acid in neuroblastoma cells. Then, using neuroblastoma cells transfected to stably overexpress the RARβ(2) gene, a SAR was developed for the indole-3-amides. Real-time PCR was also used to demonstrate their RARβ(2) agonistic activity.