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 resulted the most sensitive (pGI50 ¼ 6.68). Moreover the derivative 7-(3-Chloropropyl)-9-methyl-5- (methylsulfanyl)-8-phenyl-3H-imidazo[1,2-c]pyrrolo[3,2-e]pyrimidin-2(7H)-one showed a good antitumor activity against the leukemia subpanel with a low cytotoxic activity, above all against the HCT11 human tumour cell line. The VLAK protocol revealed a good method to design new molecules with good antitumor activity, starting from low active compounds. Moreover this protocol focused on the pyrrolo-pyrimidine derivatives as useful starting point for further development to obtain more potent antitumor agents.

Lauria, A., Patella, C., Abbate, I., Martorana, A., & Almerico, A.M. (2012). Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 55(55), 375-383 [dx.doi.org/10.1016/j.ejmech.2012.07.046].

Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents

LAURIA, Antonino;PATELLA, Chiara;ABBATE, Ilenia;MARTORANA, Annamaria;ALMERICO, Anna Maria
2012

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 resulted the most sensitive (pGI50 ¼ 6.68). Moreover the derivative 7-(3-Chloropropyl)-9-methyl-5- (methylsulfanyl)-8-phenyl-3H-imidazo[1,2-c]pyrrolo[3,2-e]pyrimidin-2(7H)-one showed a good antitumor activity against the leukemia subpanel with a low cytotoxic activity, above all against the HCT11 human tumour cell line. The VLAK protocol revealed a good method to design new molecules with good antitumor activity, starting from low active compounds. Moreover this protocol focused on the pyrrolo-pyrimidine derivatives as useful starting point for further development to obtain more potent antitumor agents.
Settore CHIM/08 - Chimica Farmaceutica
Lauria, A., Patella, C., Abbate, I., Martorana, A., & Almerico, A.M. (2012). Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 55(55), 375-383 [dx.doi.org/10.1016/j.ejmech.2012.07.046].
File in questo prodotto:
File Dimensione Formato  
EJMECH5662.pdf

Solo gestori archvio

Descrizione: 12EJMC375
Dimensione 721.2 kB
Formato Adobe PDF
721.2 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/64282
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 39
  • ???jsp.display-item.citation.isi??? 37
social impact