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
2012-01-01

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.
2012
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].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/64282
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