New annelated thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines, with potent anticancer activity, designed through VLAK protocol

Abstract Drug design was performed through the Virtual Lock-and-Key (VLAK) protocol. This in silico approach allowed to select new annelated thienotriazolopyrimidine derivatives, potentially antitumor drugs. Starting from benzothieno[2,3- e ][1,2,3]triazolo[1,5- a ]pyrimidine and Pyrido[3′,2′:4,5]thieno[2,3- e ][1,2,3]triazolo[1,5- a ]pyrimidine core structures, new derivatives of these nuclei were designed and synthesized. Three of them were selected by the Development Therapeutical Program (DTP) of the National Cancer Institute (NCI) for the anticancer screening against a panel of 60 human tumor cell lines. The biological results showed that the new derivatives exhibited an excellent antiproliferative activity reaching sub-micromolar concentration. Moreover, to be evidenced their low toxicity and high potency.