Structure-Activity Relationship Study of 16a-Thiocamptothecins: an Integrated In Vitro and In Silico Approach (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Structure-Activity Relationship Study of 16a-Thiocamptothecins: an Integrated In Vitro and In Silico Approach (Articolo in rivista) (literal)

Anno

• 2010-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1002/cmdc.201000369 (literal)

Alternative label

• Samori, C.; Beretta, G.L.; Varchi, G.; Guerrini, A.; Di Micco, S:, Basili, S.; Bifulco, G.; Riccio, R,; Moro, S.; Bombardelli, E.; Zunino, F., Fontana, G. (2010)
  Structure-Activity Relationship Study of 16a-Thiocamptothecins: an Integrated In Vitro and In Silico Approach
  in ChemMedChem (Print)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Samori, C.; Beretta, G.L.; Varchi, G.; Guerrini, A.; Di Micco, S:, Basili, S.; Bifulco, G.; Riccio, R,; Moro, S.; Bombardelli, E.; Zunino, F., Fontana, G. (literal)

Pagina inizio

• 2006 (literal)

Pagina fine

• 2015 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 5 (literal)

Rivista

• ChemMedChem (Rivista)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• 1. Indena SPA, I-20139 Milan, Italy 2. Ist CNR Sintesi Organ & Fotoreattivita ISOF, Area Ric Bologna, I-40129 Bologna, Italy 3. Fdn IRCCS Ist Nazl Tumori, Diparitmento Oncol Sperimentale & Med Mol, I-20133 Milan, Italy 4. Univ Salerno, Dipartimento Sci Farmaceut, I-84084 Fisciano, SA Italy 5. Univ Padua, MMS, Dipartimento Sci Farmaceut, I-35131 Padua, Italy (literal)

Titolo

• Structure-Activity Relationship Study of 16a-Thiocamptothecins: an Integrated In Vitro and In Silico Approach (literal)

Abstract

• The instability of the hydroxylactone E ring represents a critical drawback of camptothecins, because the lactone ring is recognized to be essential for stabilization of topoisomerase I-mediated DNA cleavage. In an attempt to investigate the effect of the thiopyridone pharmacophofore on the molecular and pharmacological features of the drug, we prepared a series of novel 16a-thiocamptothecin analogues. Due to the sulfur atom, a destabilization of the hydrogen bond between the hydroxy group in position 17 of the opened E ring and the carbonyl of the pyridone moiety is predicted, thus shifting the equilibrium toward the closed lactone form and increasing the lipophilic properties of the compounds. This feature was associated with superior antiproliferative potency, with reduced interaction with the human serum albumin and with substantial increase of the persistence of the topoisomerase I-DNA cleavable complex. These effects were prominent for thio-SN38, the most active compound of the series. The favorable interactions at the molecular and cellular level of the reported thiocamptothecins confer promising features, and these compounds warrant preclinical development. (literal)

Prodotto di

• Institute for organic syntheses and photoreactivity (ISOF) (Istituto)
• Sintesi e caratterizzazione mediante metodologie chimiche innovative, di scaffold molecolari per l'individuazione di nuove molecole biologicamente attive. (PM.P03.011.002) (Modulo)

Autore CNR

• ANDREA GUERRINI (Persona)
• GRETA VARCHI (Unità di personale interno)

Insieme di parole chiave

• Parole chiave di "Structure-Activity Relationship Study of 16a-Thiocamptothecins: an Integrated In Vitro and In Silico Approach" (Insieme di parole chiave)

Incoming links:

Prodotto

• Institute for organic syntheses and photoreactivity (ISOF) (Istituto)
• Sintesi e caratterizzazione mediante metodologie chimiche innovative, di scaffold molecolari per l'individuazione di nuove molecole biologicamente attive. (PM.P03.011.002) (Modulo)

Autore CNR di

• GRETA VARCHI (Unità di personale interno)
• ANDREA GUERRINI (Persona)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• ChemMedChem (Rivista)

Insieme di parole chiave di

• Parole chiave di "Structure-Activity Relationship Study of 16a-Thiocamptothecins: an Integrated In Vitro and In Silico Approach" (Insieme di parole chiave)