0000000001062154
AUTHOR
Ilenia Abbate
The influence of acidic pH environment in regulating the activity of novel HIF-1 inhibitors
Design and Synthesis of new Inhibitors of Carcinogenic Processes
LOOKING FOR NEW HSP-90 INHIBITORS THROUGH A MOLECULAR DOCKING/PHARMACOPHORE APPROACH
Identificazione e sintesi di nuovi potenziali inibitori di Heat Shock Protein 90
Pirazolo[3,4-d][1,2,3]triazolo[1,5-a]pirimidina: accesso sintetico tramite cicloaddizioni 1,3-dipolari e riarrangiamento di Dimroth
New annelated thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines, with potent anticancer activity, designed through VLAK protocol
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 act…
Nuovi derivati 3,5-diaril-4,5-diidropirazolici come inibitori di HSP90
An unexpected Dimroth rearrangement leading to annelated thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidines with potent antitumor activity.
An unusual Dimroth rearrangement occurring in the reaction leading to annelated thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine core allowed the isolation of the linear isomer thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidine. By decorating the linear isomer with the same chains that improved the biological activity of the angular isomers, new annelated thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidines were designed and synthesized. They were selected by the Developmental Therapeutics 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 strong antiproliferative …
Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening
The design through energy-based pharmacophore virtual screening has led to aminocyanopyridine derivatives as efficacious new inhibitors of Hsp90. The synthesized compounds showed a good affinity for the Hsp90 ATP binding site in the competitive binding assay. Moreover, they showed an excellent antiproliferative activity against a large number of human tumor cell lines. Further biological studies on the derivative with the higher EC50 confirmed its specific influence on the cellular pathways involving Hsp90.
PROGETTAZIONE, SINTESI E VALUTAZIONE BIOLOGICA DI NUOVI INIBITORI DI HSP90
Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents
Abstract The chemometric protocol VLAK was applied to predict improvement of the biological activity of pyrrolo-pyrimidine derivatives as anticancer agents, by using the NCI ACAM Database as depository of antitumor drugs with a known mechanism of action. Among the selected compounds two of these showed a good increase in the antitumor activity. These new pyrrolo-pyrimidine compounds were demonstrated effective against the full panels of NCI DTP tumour human cell lines. The derivative 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one reveled efficacious against the leukemia subpanel, in particular the RPMI cell line…
ChemInform Abstract: Pyrazolo[3,4-d][1,2,3]triazolo[1,5-a]pyrimidine: A New Ring System Through Dimroth Rearrangement.
Abstract Derivatives of the new ring system pyrazolo[3,4- d ][1,2,3]triazolo[1,5- a ]pyrimidine were synthesized from the corresponding angular isomers, through a Dimroth rearrangement, in quantitative yields. Preliminary computational studies demonstrated that this class of compounds could be a good candidate as DNA intercalating agents.
Sintesi di Nuovi Derivati del Sistema Triciclico Pirazolo[3,4-d][1,2,3]triazolo[1,5-a]pirimidinico DNA interattivi
Pyrazolo[3,4-d][1,2,3]triazolo[1,5-a]pyrimidine: a new ring system through Dimroth rearrangement
Abstract Derivatives of the new ring system pyrazolo[3,4- d ][1,2,3]triazolo[1,5- a ]pyrimidine were synthesized from the corresponding angular isomers, through a Dimroth rearrangement, in quantitative yields. Preliminary computational studies demonstrated that this class of compounds could be a good candidate as DNA intercalating agents.