2. Academic Validation
  3. Biological Evaluation in Vitro and in Silico of Azetidin-2-one Derivatives as Potential Anticancer Agents

Biological Evaluation in Vitro and in Silico of Azetidin-2-one Derivatives as Potential Anticancer Agents

  • ACS Med Chem Lett. 2016 Nov 10;8(1):32-37. doi: 10.1021/acsmedchemlett.6b00313.
Fabián E Olazaran 1,  Gildardo Rivera 2,  Alondra M Pérez-Vázquez 2,  Cynthia M Morales-Reyes 2,  Aldo Segura-Cabrera 3,  Isaías Balderas-Rentería 1
Affiliations

Affiliations

  • 1 Universidad Autonoma de Nuevo Leon , Facultad de Ciencias Químicas, Monterrey, México.
  • 2 Centro de Biotecnología Genómica, Instituto Politécnico Nacional , Reynosa, México.
  • 3 Red de Estudios Moleculares Avanzados, Instituto de Ecología , A.C., Xalapa Enríquez, México.
PMID: 28105271 DOI: 10.1021/acsmedchemlett.6b00313
Abstract

Potential Anticancer activity of 16 azetidin-2-one derivatives was evaluated showing that compound 6 [N-(p-methoxy-phenyl)-2-(p-methyl-phenyl)-3-phenoxy-azetidin-2-one] presented cytotoxic activity in SiHa cells and B16F10 cells. The Caspase-3 assay in B16F10 cells displayed that azetidin-2-one derivatives induce Apoptosis. Microarray and molecular analysis showed that compound 6 was involved on specific gene overexpression of Cytoskeleton regulation and Apoptosis due to the inhibition of some cell cycle genes. From the 16 derivatives, compound 6 showed the highest selectivity to neoplastic cells, it was an inducer of Apoptosis, and according to an in silico analysis of chemical interactions with colchicine binding site of human α/β-tubulin, the mechanism of action could be a molecular interaction involving the Amino acids outlining such binding site.

Keywords

Azetidin-2-one; anticancer; apoptosis; docking; microarray; β-tubulin.

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