title: 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.
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF", Sezione di Chimica Farmaceutica e Biologica, Università di Palermo, Via Archirafi 32, I-90123 Palermo, Italy. antonino.lauria@unipa.it
authors: Antonino
authors: A
authors: Lauria
authors: Ilenia
authors: I
authors: Abbate
authors: Chiara
authors: C
authors: Patella
authors: Annamaria
authors: A
authors: Martorana
authors: Gaetano
authors: G
authors: Dattolo
authors: Anna Maria
authors: AM
authors: Almerico
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013876:Thiophenes; D014230:Triazoles