Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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, Ferla, Salvatore, 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

[img]
Preview
PDF - Accepted Post-Print Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB) | Preview

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: 30 Jul 2019 02:05
URI: http://orca.cf.ac.uk/id/eprint/113241

Citation Data

Cited 1 time in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics