TY - JOUR
T1 - Biological evaluation in vitro and in silico of azetidin-2-one derivatives as potential anticancer agents
AU - Olazaran, Fabián E.
AU - Rivera, Gildardo
AU - Pérez-Vázquez, Alondra M.
AU - Morales-Reyes, Cynthia M.
AU - Segura-Cabrera, Aldo
AU - Balderas-Rentería, Isaías
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2017/1/12
Y1 - 2017/1/12
N2 - 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.
AB - 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.
KW - Anticancer
KW - Apoptosis
KW - Azetidin-2-one
KW - Docking
KW - Microarray
KW - β-tubulin
UR - http://www.scopus.com/inward/record.url?scp=85037331933&partnerID=8YFLogxK
U2 - 10.1021/acsmedchemlett.6b00313
DO - 10.1021/acsmedchemlett.6b00313
M3 - Artículo
C2 - 28105271
SN - 1948-5875
VL - 8
SP - 32
EP - 37
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
IS - 1
ER -