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 antitumoractivity 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.
|Numero di pagine||9|
|Rivista||European Journal of Medicinal Chemistry|
|Stato di pubblicazione||Published - 2012|
All Science Journal Classification (ASJC) codes
- Drug Discovery
- Organic Chemistry
Martorana, A., Lauria, A., Almerico, A. M., Patella, C., & Abbate, I. (2012). Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents. European Journal of Medicinal Chemistry, 55, 375-383.