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

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

  • Bioorg Med Chem. 2015 Oct 1;23(19):6305-16. doi: 10.1016/j.bmc.2015.08.027.
Demetrio Raffa 1,  Benedetta Maggio 2,  Fabiana Plescia 3,  Stella Cascioferro 3,  Maria Valeria Raimondi 3,  Gabriella Cancemi 3,  Antonella D'Anneo 4,  Marianna Lauricella 5,  Maria Grazia Cusimano 3,  Ruoli Bai 6,  Ernest Hamel 6,  Giuseppe Daidone 3
Affiliations

Affiliations

  • 1 Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy. Electronic address: demetrio.raffa@unipa.it.
  • 2 Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy. Electronic address: benedetta.maggio@unipa.it.
  • 3 Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123 Palermo, Italy.
  • 4 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, 90123 Palermo, Italy.
  • 5 Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Biochemistry, University of Palermo, 90123 Palermo, Italy.
  • 6 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.
PMID: 26344588 DOI: 10.1016/j.bmc.2015.08.027
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-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.

Keywords

2-(2-Phenoxyacetamido)benzamides; Antiproliferative activity; Apoptosis; G0/G1 arrest; Pro-caspase 3.

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