A new series of 3-benzoylamino-5-imidazol-5-yl-benzo[b]thiophenes and the parent amino derivatives were synthesized and screened as antitumor agents. All tested compounds showed concentration-dependent antiproliferative activity profile against HeLa cell line, exhibiting GI50 values in the low micromolar range. The most active compounds were tested in cell cycle perturbation experiments. A rapid accumulation of cells in the G2/M phase, with a concomitant reduction of cells in both the S and G0/G1 phases, was observed, suggesting that cell exposure to selected derivatives produces mitotic failure. To rationalize the biological results, the 3-benzoylamino-benzo[b]thiophenes were analyzed through the in silico VLAK protocol. Compounds presenting the 3,4,5-trimethoxy-benzoyl moiety were in silico classified as potential antimitotic agents or topoisomerase II inhibitors, in good agreement with the biological studies.
Martorana, A., Gentile, C., Perricone, U., Palumbo Piccionello, A., Bartolotta, R., Terenzi, A., et al. (2015). Synthesis, antiproliferative activity, and in silico insights of new 3-benzoylamino-benzo[ b ]thiophene derivatives. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 90, 537-546 [10.1016/j.ejmech.2014.12.002].
Synthesis, antiproliferative activity, and in silico insights of new 3-benzoylamino-benzo[ b ]thiophene derivatives
MARTORANA, Annamaria;GENTILE, Carla;Perricone, Ugo;PALUMBO PICCIONELLO, Antonio;BARTOLOTTA, Roberta;TERENZI, Alessio;PACE, Andrea;ALMERICO, Anna Maria;LAURIA, Antonino
2015-01-01
Abstract
A new series of 3-benzoylamino-5-imidazol-5-yl-benzo[b]thiophenes and the parent amino derivatives were synthesized and screened as antitumor agents. All tested compounds showed concentration-dependent antiproliferative activity profile against HeLa cell line, exhibiting GI50 values in the low micromolar range. The most active compounds were tested in cell cycle perturbation experiments. A rapid accumulation of cells in the G2/M phase, with a concomitant reduction of cells in both the S and G0/G1 phases, was observed, suggesting that cell exposure to selected derivatives produces mitotic failure. To rationalize the biological results, the 3-benzoylamino-benzo[b]thiophenes were analyzed through the in silico VLAK protocol. Compounds presenting the 3,4,5-trimethoxy-benzoyl moiety were in silico classified as potential antimitotic agents or topoisomerase II inhibitors, in good agreement with the biological studies.File | Dimensione | Formato | |
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