The Role of Polyamine Architecture on the Pharmacological Activity of Open Lactone Camptothecin-Polyamine Conjugates (Articolo in rivista)

Type
Label
  • The Role of Polyamine Architecture on the Pharmacological Activity of Open Lactone Camptothecin-Polyamine Conjugates (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/bc800033r (literal)
Alternative label
  • Cristian Samorì (1);* Andrea Guerrini (1); Greta Varchi (1); Giovanni Luca Beretta (2); Gabriele Fontana (3); Ezio Bombardelli (3); Nives Carenini (2); Franco Zunino (2); Carlo Bertucci (4); Jessica Fiori (4); Arturo Battaglia (1) (2008)
    The Role of Polyamine Architecture on the Pharmacological Activity of Open Lactone Camptothecin-Polyamine Conjugates
    in Bioconjugate chemistry
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cristian Samorì (1);* Andrea Guerrini (1); Greta Varchi (1); Giovanni Luca Beretta (2); Gabriele Fontana (3); Ezio Bombardelli (3); Nives Carenini (2); Franco Zunino (2); Carlo Bertucci (4); Jessica Fiori (4); Arturo Battaglia (1) (literal)
Pagina inizio
  • 2270 (literal)
Pagina fine
  • 2279 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 19 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 11 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • (1) Istituto CNR per la Sintesi Organica e Fotoreattivita` \"I.S.O.F.\", Area della Ricerca di Bologna, Via Gobetti 101, 40129 Bologna, Italy (2) Dipartimento di Oncologia Sperimentale e Laboratori, Fondazione IRCCS Istituto Nazionale Tumori 20133 Milano, Italy (3) Indena SPA, viale Ortles 12, 20139 Milano, Italy (4) Dipartimento di Scienze Farmaceutiche, Universita`di Bologna, Via Belmeloro 6, 40126 Bologna, Italy (literal)
Titolo
  • The Role of Polyamine Architecture on the Pharmacological Activity of Open Lactone Camptothecin-Polyamine Conjugates (literal)
Abstract
  • A series of camptothecin open-ring lactone tripartate conjugates were synthesized, in which polyamine side chains with different architecture (ethane-1,2-diamine, spermidine, homospermidine, spermine, and 4,8,13,17-tetrazaicosane-1,20-diamine) are linked to the 21-carboxylic function through an amidic bond, while the 17-CH2OH is acetylated. The rationale for the synthesis of these compounds was to explore the influence of the polyamine architecture on the activity of these CPT conjugates into cells, since the positively charged ammonium cations would favor interaction through electrostatic binding to the negatively charged DNA backbone. Topoisomerase I-mediated DNA cleavage assay was used to investigate the ability of these compounds to stimulate the DNA damage. The cleavage pattern was found to be similar to that of SN38 for all the new CPTs. The CPT tripartates were tested for growth inhibition ability against the human non-small-cell lung cancer carcinoma NCI-H460 cell line. Although these compounds were less potent than topotecan, SN38, and CPT after I h of treatment, the antiproliferative effects greatly increased after 72 In of exposure. The growth inhibition potency during long-term exposure is correlated with the number of charges of the 21-amide substituent. Both cleavage assay and in vitro effects support the interpretation that the compounds may have inhibitory activity also in the open-ring form. The architecture of the polyamine moiety is important for antiproliferative activity, and a balance between the hydrophilic and lipophilic properties of the polyamine is critical for CPT potency. (literal)
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