Synthesis, antiproliferative activity and possible mechanism of action of novel 2-acetamidobenzamides bearing the 2-phenoxy functionality

具有 2-苯氧基官能团的新型 2-乙酰氨基苯甲酰胺的合成、抗增殖活性和可能的作用机制

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作者:Demetrio Raffa, Benedetta Maggio, Fabiana Plescia, Stella Cascioferro, Maria Valeria Raimondi, Gabriella Cancemi, Antonella D'Anneo, Marianna Lauricella, Maria Grazia Cusimano, Ruoli Bai, Ernest Hamel, Giuseppe Daidone

Abstract

Several new 2-(2-phenoxyacetamido)benzamides 17a-v, 21 and 22 were synthesized by stirring in pyridine the acid chlorides 16a-e and the appropriate5-R-4-R&sub1;-2-aminobenzamide 15a-e and initially evaluated in vitro for antiproliferative activity against the K562 (human chronic myelogenous leukemia) cell line. Some of synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). The most active compounds caused an arrest of K562 cells in the G0-G1 phase of cell cycle and induction of apoptosis, which was mediated by caspase activation.

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