Synthesis, antiproliferative activity and possible mechanism of action of novel 2-acetamidobenzamides bearing the 2-phenoxy functionality.
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-R₁-2-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.
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy. Electronic address: demetrio.raffa@unipa.it.
Demetrio
D
Raffa
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy. Electronic address: benedetta.maggio@unipa.it.
Benedetta
B
Maggio
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy.
Fabiana
F
Plescia
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy.
Stella
S
Cascioferro
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy.
Maria Valeria
MV
Raimondi
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy.
Gabriella
G
Cancemi
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, 90123 Palermo, Italy.
Antonella
A
D'Anneo
Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Biochemistry, University of Palermo, 90123 Palermo, Italy.
Marianna
M
Lauricella
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy.
Maria Grazia
MG
Cusimano
Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Ruoli
R
Bai
Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Ernest
E
Hamel
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy.
Giuseppe
G
Daidone
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D008856:Microscopy, Fluorescence; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001549:Benzamides; C037689:benzamide; D020169:Caspases
2-(2-Phenoxyacetamido)benzamides; Antiproliferative activity; Apoptosis; G0/G1 arrest; Pro-caspase 3