6533b82afe1ef96bd128b8d4

RESEARCH PRODUCT

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

Chiara PatellaAntonino LauriaIlenia AbbateAnna Maria AlmericoGaetano DattoloAnnamaria Martorana

subject

PyrimidineStereochemistryAntineoplastic AgentsThiophenesStructure-Activity Relationshipchemistry.chemical_compoundCell Line TumorDrug DiscoveryHumansStructure–activity relationshipPotencyAnnelated thienotriazolopyrimidines Domino reactions VLAK protocol Developmental Therapeutics Program (DTP) Anticancer agentsCell ProliferationPharmacologyDose-Response Relationship DrugMolecular StructureLow toxicityOrganic ChemistryGeneral MedicineTriazolesCombinatorial chemistrySettore CHIM/08 - Chimica FarmaceuticaHuman tumorPyrimidineschemistryDrug Screening Assays Antitumor

description

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.

yearjournalcountryeditionlanguage
2012-11-28
http://hdl.handle.net/10447/73054