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

Abstract

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.

• Authors: Christopher R Gardner, Belamy B Cheung, Jessica Koach, David StC Black, Glenn M Marshall, Naresh Kumar
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 20 Issue 23 Pg. 6877-84 (Dec 01 2012) ISSN: 1464-3391 [Electronic] England
• PMID: 23088909 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzothiazoles
• Dipeptides
• Indoles
• Receptors, Retinoic Acid
• aminobenzothiazole compound
• retinoic acid receptor, beta2, human
• Isotretinoin

Topics

• Adenocarcinoma (drug therapy)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzothiazoles (chemical synthesis, chemistry, pharmacology)
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Cell Survival
• Dipeptides (chemical synthesis, chemistry)
• Female
• Humans
• Indoles (chemical synthesis, chemistry, pharmacology)
• Isotretinoin (pharmacology)
• Neuroblastoma (drug therapy)
• Receptors, Retinoic Acid (agonists)