Romagnoli, Romeo, Baraldi, Pier Giovanni, Prencipe, Filippo, Oliva, Paola, Baraldi, Stefania, Tabrizi, Mojgan Aghazadeh, Lopez-Cara, Luisa Carlota, Ferla, Salvatore  ORCID: https://orcid.org/0000-0002-5918-9237, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Hamel, Ernest, Ronca, Roberto, Bortolozzi, Roberta, Mariotto, Elena, Basso, Giuseppe and Viola, Giampietro
2016.
Design and synthesis of potent in vitro and in vivo anticancer agents based on 1-(3′,4′,5′-Trimethoxyphenyl)-
2-Aryl-1H-Imidazole.
Scientific Reports
6
, p. 26602.
10.1038/srep26602
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Abstract
A novel series of tubulin polymerization inhibitors, based on the 1-(3′,4′,5′-trimethoxyphenyl)-2-aryl-1H-imidazole scaffold and designed as cis-restricted combretastatin A-4 analogues, was synthesized with the goal of evaluating the effects of various patterns of substitution on the phenyl at the 2-position of the imidazole ring on biological activity. A chloro and ethoxy group at the meta- and para-positions, respectively, produced the most active compound in the series (4o), with IC50 values of 0.4-3.8 nM against a panel of seven cancer cell lines. Except in HL-60 cells, 4o had greater antiproliferative than CA-4, indicating that the 3′-chloro-4′-ethoxyphenyl moiety was a good surrogate for the CA-4 B-ring. Experiments carried out in a mouse syngenic model demonstrated high antitumor activity of 4o, which significantly reduced the tumor mass at a dose thirty times lower than that required for CA-4P, which was used as a reference compound. Altogether, our findings suggest that 4o is a promising anticancer drug candidate that warrants further preclinical evaluation.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Pharmacy |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology |
| Publisher: | Nature Publishing Group |
| ISSN: | 2045-2322 |
| Date of First Compliant Deposit: | 11 June 2016 |
| Date of Acceptance: | 3 May 2016 |
| Last Modified: | 05 Jan 2024 06:00 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/91753 |
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