TY - CONF
T1 - Synthesis, antiproliferative activity, and mechanism of action of new benzamido derivatives
AU - Raffa, Demetrio
AU - Cascioferro, Stella Maria
AU - Cusimano, Maria Grazia
AU - Plescia, Fabiana
AU - Maggio, Benedetta
AU - Raimondi, Maria Valeria
AU - Daidone, Giuseppe
PY - 2011
Y1 - 2011
N2 - The cinnamoyl anthranilamides represent a class of biological active substances of great importance in medicinal chemistry. Moreover, despite their wide range of biological activities, a review of the literature revealed that no anticancer activity is described for this kind of substances. Starting from the 2-cinnamamido-5-iodobenzamide, resulted able to inhibit the leukemic cell line K-562 proliferation with a percent of inhibition of 74% at 10M concentration, we undertake the following structural modifications on cinnamamidobenzamide skeleton: the introduction of various substituents both on the benzamido and the cinnamamido moieties, the substitution of olefinic bond with the ethane, ethyne, cyclopropane and phenyl groups.Synthesized compounds caused growth inhibition against many tumor cell lines at low micromolar and submicromolar concentrations against every tumor cell line investigated The best activity was obtained when the 5 position of the benzamido moiety was substituted with an iodine moiety. COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution (G2-M phase block), including induction of apoptosis, indicate that these new antiproliferative compounds act as antitubulin agents. Preliminary biological data on 2-(3-phenylpropiolamido)benzamides, bearing an ethyne bond, showed a different mechanism of action considering that they caused a G0-G1 block of the cell cycle on K526 cell line.
AB - The cinnamoyl anthranilamides represent a class of biological active substances of great importance in medicinal chemistry. Moreover, despite their wide range of biological activities, a review of the literature revealed that no anticancer activity is described for this kind of substances. Starting from the 2-cinnamamido-5-iodobenzamide, resulted able to inhibit the leukemic cell line K-562 proliferation with a percent of inhibition of 74% at 10M concentration, we undertake the following structural modifications on cinnamamidobenzamide skeleton: the introduction of various substituents both on the benzamido and the cinnamamido moieties, the substitution of olefinic bond with the ethane, ethyne, cyclopropane and phenyl groups.Synthesized compounds caused growth inhibition against many tumor cell lines at low micromolar and submicromolar concentrations against every tumor cell line investigated The best activity was obtained when the 5 position of the benzamido moiety was substituted with an iodine moiety. COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution (G2-M phase block), including induction of apoptosis, indicate that these new antiproliferative compounds act as antitubulin agents. Preliminary biological data on 2-(3-phenylpropiolamido)benzamides, bearing an ethyne bond, showed a different mechanism of action considering that they caused a G0-G1 block of the cell cycle on K526 cell line.
KW - Benzamido derivatives
KW - antiproliferative activity
KW - cell cycle
KW - Benzamido derivatives
KW - antiproliferative activity
KW - cell cycle
UR - http://hdl.handle.net/10447/61620
UR - http://www.sci2011.unisalento.it/index.php?option=com_docman&task=cat_view&gid=35&Itemid=36
M3 - Other
SP - 394
EP - 394
ER -