1. Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides
- Author
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Demetrio Raffa, Fiorella Meneghetti, Rosaria Maria Pipitone, Gabriella Bombieri, Stella Cascioferro, Domenico Schillaci, Giuseppe Daidone, Manlio Tolomeo, Antonietta Di Cristina, Stefania Grimaudo, Salvatore Plescia, Benedetta Maggio, Giorgio Gallo, Maria Valeria Raimondi, RAFFA, D, MAGGIO, B, CASCIOFERRO, SM, RAIMONDI, MV, SCHILLACI, D, GALLO, G, DAIDONE, G, PLESCIA, S, MENEGHETTI, F, BOMBIERI, G, DI CRISTINA, A, PIPITONE, RM, GRIMAUDO, S, and TOLOMEO, M
- Subjects
Indazoles ,Antineoplastic Agents ,Crystallography, X-Ray ,Retinoblastoma Protein ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,medicine ,Humans ,Cell Proliferation ,G0-G1 arrest ,Pharmacology ,Indazole ,Molecular Structure ,Chemistry ,Cell growth ,Melanoma ,Organic Chemistry ,Cell Cycle ,Cancer ,1H-Indazole-1-carboxamides ,Crystallographic study ,pRb ,1H-Indazole-1-carboxamide ,General Medicine ,Cell cycle ,medicine.disease ,Amides ,Settore CHIM/08 - Chimica Farmaceutica ,In vitro ,Crystallographyc study ,Leukemia ,Biochemistry ,Neoplastic cell - 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 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting antiproliferative activity. The most active compounds of this series, 10d,e, were able to inhibit cell growth of many neoplastic cell lines at concentrations lower than 1 μM (0.0153 μM 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.
- Published
- 2009