Design, Synthesis and Anticancer Biological Evaluation of Novel 1,4-Diaryl- 1,2,3-triazole Retinoid Analogues of Tamibarotene (AM80)

Mariana Aleixo,Marcos Amaral,Luiz Viana,Adriano Baroni,Maria Matos,Marilin Cunha,Renata Perdomo,Najla Kassab,Diego Carvalho,Taís Garcia,Indiara Pereira,Palimécio Guerrero Jr

doi:10.21577/0103-5053.20170119

Mariana Aleixo, Marcos Amaral + Show 10 more

Open Access

PDF Available

https://doi.org/10.21577/0103-5053.20170119

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

We report herein the design and synthesis via click chemistry of twelve novel triazole retinoid analogues of tamibarotene (AM80) and the evaluation of their anticancer activities against six cancer cell lines: HL60, K562, 786, HT29, MCF7 and PC3. Among the synthesized compounds, two were more potent than tamibarotene against solid tumor cells, and one of them had similar potency to tamibarotene against HL60 cells. The bioisosteric exchange between the amide group and the 1,2,3-triazole core in the retinoid agent tamibarotene (AM80) reported in this work is a valid strategy for the generation of useful compounds against cancer.

Highlights

In recent years, cancers have been responsible for 8.2 million human deaths worldwide.[1,2] The rising demand for effective and safer anticancer drugs has led several research groups to develop new strategies to synthesize a wide range of anticancer molecules and to evaluate their biological anticancer activities.[2]Retinoids are class of chemical compounds that are derivatives of vitamin A with a large number of biological processes.[3]
The biological effects of retinoids result from their modulation of retinoic acid receptors (RARs) and retinoic X receptors (RXRs), each having three target
Some important characteristics of click reactions in organic synthesis are their modular nature, high yields of products, broad scope, ability to isolate products without chromatographic methods, use of solvents with low toxicity, and stereospecificity, which makes these methods very useful in organic synthesis.[18]. Another important characteristic of the click chemistry approach in medicinal chemistry is the possibility to rapidly synthesize a library of compounds with broad structural diversification in order to obtain new molecules with improved biological activity.[19]

Summary

Introduction

Cancers have been responsible for 8.2 million human deaths worldwide.[1,2] The rising demand for effective and safer anticancer drugs has led several research groups to develop new strategies to synthesize a wide range of anticancer molecules and to evaluate their biological anticancer activities.[2]Retinoids are class of chemical compounds that are derivatives of vitamin A with a large number of biological processes.[3]. Cancers have been responsible for 8.2 million human deaths worldwide.[1,2] The rising demand for effective and safer anticancer drugs has led several research groups to develop new strategies to synthesize a wide range of anticancer molecules and to evaluate their biological anticancer activities.[2]. The biological effects of retinoids result from their modulation of retinoic acid receptors (RARs) and retinoic X receptors (RXRs), each having three target. The molecular structures of retinoids can be divided into three parts: a hydrophobic region, a linker unit, and Design, Synthesis and Anticancer Biological Evaluation of Novel 1,4-Diaryl-1,2,3-triazole Among several retinoid anticancer compounds, here we consider the pan-RAR agonists ATRA 1 (natural ligand)[3,4,5] and TTNPB 2 (synthetic ligand),[3,4,5] the pan-RXR agonist bexarotene 3,3-9 the selective RARα receptor synthetic agonists AM80 43-9 and AM580 5,3-9 and UVI2007 6, an RARβ agonist[10] (Figure 1).

Objectives

Results

Conclusion