Synthesis and biological evaluation of novel 6-alkoxy-3-aryl-[1,2,4]triazolo[4,3-b][1,2,4,5] tetrazines

Abstract

A series of 6-alkoxy-3-aryl-[1,2,4]triazolo[4,3- b][1,2,4,5] tetrazine derivatives is synthesized and evaluated for their antitumor activities. These compounds exhibit potent antiproliferative activities against A549, Bewo, and MCF-7 cells. Molecular docking is performed to study the inhibitor–c-Met kinase interactions, and the results show that 6-ethoxyl-3-phenylethyl-[1,2,4]triazolo[4,3- b][1,2,4,5] tetrazine is potently bound to c-Met kinase with two hydrogen bonds and one π–π interaction. Based on these preliminary results, it is thought that compound 6-ethoxyl-3-phenylethyl-[1,2,4]triazolo[4,3- b][1,2,4,5] tetrazine with potent inhibitory activity may be a potential anticancer agent.

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

“…At the same time, azolo-annulated 1,2,4,5-tetrazines remain to be a scarcely studied class of compounds, mainly due to the lack of convenient methods for their synthesis and modification. For example, synthesis and properties of some [1,2,4]triazolo [4,3-b] [1,2,4,5]tetrazine derivatives are described in the literature [15,16,32,33]. However isomeric [1,2,4]triazolo [1,5b] [1,2,4,5]tetrazines are currently unknown.…”

“…Up to date, there is a considerable data set, providing an evidence that azolo-annulated 1,2,4,5-tetrazines have a pronounced biological activity. It is worth, for instance, to mention antimicrobial activity of 1,4-dihydroimidazo[1,2- b ][1,2,4,5]tetrazines [ 3 ], antibacterial, antifungal, and anti-infammatory activities of dihydro- and tetrahydro[1,2,4]triazolo[4,3- b ][1,2,4,5]tetrazines [ 4 – 6 ], antituberculosis activity of [1,2,4]triazolo[4,3- b ]- and imidazo[1,2- b ][1,2,4,5]tetrazines [ 7 – 9 ], antibacterial and fungistatic action of thiazolo[3,2- b ][1,2,4,5]tetrazines [ 10 ], fungistatic activity of imidazo[1,2- b ][1,2,4,5]tetrazines [ 11 ], antibacterial and antiglycation activity of imidazo[1,2- b ]- and [1,2,4]triazolo[4,3- b ][1,2,4,5]tetrazines [ 12 – 14 ] as well as antitumor activity of [1,2,4]triazolo[4,3- b ][1,2,4,5]tetrazines [ 15 – 16 ] and imidazo[1,2- b ][1,2,4,5]tetrazines [ 17 – 18 ]. Thus, a search for new effective drugs in the series of azolo[1,2,4,5]tetrazines appears to be an important and promising area of research.…”