New arylthioindoles and related bioisosteres at the sulfur bridging group. 4. Synthesis, tubulin polymerization, cell growth inhibition, and molecular modeling studies

La Regina, Giuseppe, Sarkar, Taradas, Bai, Ruoli., Edler, Michael C., Saletti, Roberto, Coluccia, Antonio, Piscitelli, Francesco, Minelli, Lara, Gatti, Valerio, Mazzoccoli, Carmela., Palermo, Vanessa, Mazzoni, Cristina, Falcone, Claudio, Scovassi, Anna Ivana, Giansanti, Vincenzo, Campiglia, Pietro, Porta, Amalia, Maresca, Bruno, Hamel, Ernest, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Novellino, Ettore and Silvestri, Romano 2009. New arylthioindoles and related bioisosteres at the sulfur bridging group. 4. Synthesis, tubulin polymerization, cell growth inhibition, and molecular modeling studies. Journal of Medicinal Chemistry 52 (23) , pp. 7512-7527. 10.1021/jm900016t

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Abstract

New arylthioindoles along with the corresponding ketone and methylene compounds were potent tubulin assembly inhibitors. As growth inhibitors of MCF-7 cells, sulfur derivatives were superior or sometimes equivalent to the ketones, while methylene derivatives were substantially less effective. Esters 24, 27−29, 36, 39, and 41 showed 50% of inhibition on human HeLa and HCT116/chr3 cells at 0.5 μM, and these compounds inhibited the growth of HEK, M14, and U937 cells with IC50’s in the 78−220 nM range. While murine macrophage J744.1 cell growth was significantly less affected (20% at higher concentrations), four other nontransformed cell lines remained sensitive to these esters. The effect of drug treatment on cell morphology was examined by time-lapse microscopy. In a protocol set up to evaluate toxicity on the Saccharomyces cerevisiae BY4741 wild type strain, compounds 24 and 54 strongly reduced cell growth, and 29, 36, and 39 also showed significant inhibition.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Publisher:	American Chemical Society
ISSN:	0022-2623
Last Modified:	05 Jan 2024 05:55
URI:	https://orca.cardiff.ac.uk/id/eprint/6607

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