Synthesis of new triazole arotinoids analogues via "Click Chemistry" with potential anticancer activity

• Published in: Orbital : The Electronic Journal of Chemistry Vol. 4; no. 1; pp. 41 - 42
• Main Authors: Mariana A. A. Aleixo, Tais M. Garcia, Tatiana C. Bortolo, Diego B. Carvalho, Luiz H. Viana, Gabriela R. Hurtado, Maria F. C. Matos, Adriano C. M. Baroni
• Format: Journal Article
• Language: English
• Published: Universidade Federal de Mato Grosso do Sul 01.06.2012
• Subjects: anticancer activity; bioisosterism; click chemistry; huisgen cycloaddition; triazole analogues
• ISSN: 1984-6428
• DOI: 10.17807/orbital.v4i1.358

Retinoids are  a  class  of  natural  and  synthetic  vitamin A analogues structurally related to all-trans-retinoic acid (ATRA). This class of compounds can inhibit cell proliferation and induce differentiation and apoptosis of cells, and several are used in cancer therapy. Using the concept of bioisosterism, new triazole analogues were designed from the molecular modification of the potent derivative arotinoid AM580. This compound has an amide grouping which is a bioisostere of 1,2,3-triazole ring. Through "Click Chemistry” approach, triazole analogues were obtained by reaction of Huisgen 1,3-dipolar cycloaddition between aryl azides and terminal acetylene, previously synthesized. The reagents used were CuI, triethylamine and mixture of ethanol:water. The first compound synthesized showed anticancer activity, while the second proved to be inactive. The molecular docking results showed that both compounds have high affinity for the retinoid RARα receptor (related to anticancer activity), but probably the second compound has antagonist activity on this receptor.