TY - JOUR
T1 - New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer
AU - La Regina, Giuseppe
AU - Bai, Ruoli
AU - Coluccia, Antonio
AU - Famiglini, Valeria
AU - Pelliccia, Sveva
AU - Passacantilli, Sara
AU - Mazzoccoli, Carmela
AU - Ruggieri, Vitalba
AU - Sisinni, Lorenza
AU - Bolognesi, Alessio
AU - Rensen, Whilelmina Maria
AU - Miele, Andrea
AU - Nalli, Marianna
AU - Alfonsi, Romina
AU - Di Marcotullio, Lucia
AU - Gulino, Alberto
AU - Brancale, Andrea
AU - Novellino, Ettore
AU - Dondio, Giulio
AU - Vultaggio, Stefania
AU - Varasi, Mario
AU - Mercurio, Ciro
AU - Hamel, Ernest
AU - Lavia, Patrizia
AU - Silvestri, Romano
PY - 2014/8/14
Y1 - 2014/8/14
N2 - We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both the 1-phenyl ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARAP 22 showed strong inhibition of the P-glycoprotein-overexpressing NCI-ADR-RES and Messa/Dx5MDR cell lines. Compounds 22 and 27 suppressed in vitro the Hedgehog signaling pathway, strongly reducing luciferase activity in SAG treated NIH3T3 Shh-Light II cells, and inhibited the growth of medulloblastoma D283 cells at nanomolar concentrations. ARAPs 22 and 27 represent a new potent class of tubulin polymerization and cancer cell growth inhibitors with the potential to inhibit the Hedgehog signaling pathway.
AB - We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both the 1-phenyl ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARAP 22 showed strong inhibition of the P-glycoprotein-overexpressing NCI-ADR-RES and Messa/Dx5MDR cell lines. Compounds 22 and 27 suppressed in vitro the Hedgehog signaling pathway, strongly reducing luciferase activity in SAG treated NIH3T3 Shh-Light II cells, and inhibited the growth of medulloblastoma D283 cells at nanomolar concentrations. ARAPs 22 and 27 represent a new potent class of tubulin polymerization and cancer cell growth inhibitors with the potential to inhibit the Hedgehog signaling pathway.
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U2 - 10.1021/jm500561a
DO - 10.1021/jm500561a
M3 - Article
C2 - 25025991
AN - SCOPUS:84906094556
SN - 0022-2623
VL - 57
SP - 6531
EP - 6552
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 15
ER -