3-Aryl/Heteroaryl-5-amino-1-(3′,4′,5′-trimethoxybenzoyl)-1,2,4-triazoles as antimicrotubule agents. design, synthesis, antiproliferative activity and inhibition of tubulin polymerization

Romagnoli, Romeo, Prencipe, Filippo, Oliva, Paola, Baraldi, Stefania, Baraldi, Pier Giovanni, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Ferla, Salvatore ORCID: https://orcid.org/0000-0002-5918-9237, Hamel, Ernest, Bortolozzi, Roberta and Viola, Giampietro 2018. 3-Aryl/Heteroaryl-5-amino-1-(3′,4′,5′-trimethoxybenzoyl)-1,2,4-triazoles as antimicrotubule agents. design, synthesis, antiproliferative activity and inhibition of tubulin polymerization. Bioorganic Chemistry 80 , pp. 361-374. 10.1016/j.bioorg.2018.06.037

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Abstract

Many natural and synthetic substances are known to interfere with the dynamic assembly of tubulin, preventing the formation of microtubules. In our search for potent and selective antitumor agents, a novel series of 1-(3′,4′,5′-trimethoxybenzoyl)-5-amino-1,2,4-triazoles were synthesized. The compounds had different heterocycles, including thiophene, furan or the three isomeric pyridines, and they possessed a phenyl ring bearing electron-releasing or electron-withdrawing substituents at the 3-position of the 5-amino-1,2,4-triazole system. Most of the twenty-two tested compounds showed moderate to potent antiproliferative activities against a panel of solid tumor and leukemic cell lines, with four (5j, 5k, 5o and 5p) showing strong antiproliferative activity (IC50 < 1 μM) against selected cancer cells. Among them, several molecules preferentially inhibited the proliferation of leukemic cell lines, showing IC50 values 2-100-fold lower for Jurkat and RS4;11 cells than those for the three lines derived from solid tumors (HeLa, HT-29 and MCF-7 cells). Compound 5k strongly inhibited tubulin assembly, with an IC50 value of 0.66 μM, half that obtained in simultaneous experiments with CA-4 (IC50 = 1.3 μM).

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Pharmacy
Publisher:	Elsevier
ISSN:	0045-2068
Date of First Compliant Deposit:	17 July 2018
Date of Acceptance:	29 June 2018
Last Modified:	06 Nov 2024 14:30
URI:	https://orca.cardiff.ac.uk/id/eprint/113241

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