69843-99-8Relevant academic research and scientific papers
Anticancer activity of triazolo-thiadiazole derivatives and inhibition of akt1 and akt2 activation
Trafalis, Dimitrios T.,Sagredou, Sofia,Dalezis, Panayiotis,Voura, Maria,Fountoulaki, Stella,Nikoleousakos, Nikolaos,Almpanakis, Konstantinos,Deligiorgi, Maria V.,Sarli, Vasiliki
, (2021/04/27)
The fusion of 1,2,4-triazole and 1,3,4-thiadiazole rings results in a class of heterocycles compounds with an extensive range of pharmacological properties. A series of 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles was synthesized and tested for its enzyme inhibition potential and anticancer activity. The results show that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles display potent anticancer properties in vitro against a panel of cancer cells and in vivo efficacy in HT-29 human colon tumor xenograft in CB17 severe combined immunodeficient (SCID) mice. Preliminary mechanistic studies revealed that KA25 and KA39 exhibit time-and concentration-dependent inhibition of Akt Ser-473 phosphorylation. Molecular modeling experiments indicated that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles bind well to the ATP binding site in Akt1 and Akt2. The low acute toxicity combined with in vitro and in vivo anticancer activity render triazolo[3,4-b]thiadiazoles KA25, KA26, and KA39 promising cancer therapeutic agents.
