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GIUSEPPE DAIDONE

Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides

  • Autori: Raffa, D.; Maggio, B.; Cascioferro, S.; Raimondi, M.; Schillaci, D.; Gallo, G.; Daidone, G.; Plescia, S.; Meneghetti, F.; Bombieri, G.; DI CRISTINA, A.; Pipitone, R.; Grimaudo, S.; Tolomeo, M.
  • Anno di pubblicazione: 2009
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: 1H-Indazole-1-carboxamides; Crystallographyc study; G0-G1 arrest; pRb

Abstract

A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that the 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting anti-proliferative activity. The most active compounds of this series, 10d and 10e, were able to inhibit cell growth of many neoplastic cell lines at concentrations lower than 1µM (0.0153µM in SR leukemia) causing a block in G0-G1 phase of cell cycle. Analysis of pRb expression showed that these two compounds increased the ratio between underphosphorylated pRb and total pRb. The X-ray structure of 10w, confirmed the 3-amino-N-phenyl-1H-indazole-1-carboxamide structure of compounds 10.

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