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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Pharmaceuticals (Basel, Switzerland)
2024
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| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39598364/ |
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Table of Contents:
- Novel Thiazole-Fused [4,5-] or [5,4-]Quinazolin-8-ones and Their Quinazoline Analogues: Synthesis and Biological Evaluation. Broudic, Nathan Pacheco-Benichou, Alexandra Corbière, Cécile Baratte, Blandine Robert, Thomas Bach, Stéphane Solhi, Hélène Le Guével, Rémy Fruit, Corinne Besson, Thierry In connection with previous work on V-shaped polycyclic thiazolo[5,4-]quinazolin-9-one and [5,4-]quinazoline derivatives that can modulate the activity of various kinases, the synthesis of straight thiazole-fused [4,5-] or [5,4-]quinazolin-8-ones and quinazoline derivatives hitherto undescribed was envisioned. An innovative protocol allowed to obtain the target structures. The synthesis of inverted thiazolo[4,5-] and [5,4-]quinazolin-8-one derivatives was also explored with the aim of comparing biological results. The compounds obtained were tested against a representative panel of eight mammalian protein kinases of human origin: CDK9/CyclinT, Haspin, Pim-1, GSK-3β, CK-1ε, JAK3, CLK1 and DYRK1A. The results obtained show that the novel linear thiazoloquinazolines are not kinase inhibitors. The cytotoxicity of these newly synthesized compounds was assessed against seven representative tumor cell lines (human cancers: Huh7-D12, Caco-2, HCT-116, MCF-7, MDA-MB-231, MDA-MB-468 and PC-3). The majority of these novel molecules proved capable of inhibiting the growth of the tested cells. The 7-Benzyl-8-oxo-7,8-dihydrothiazolo[5,4-]quinazolinones and are the most potent, with IC values in the micromolar range. None of these compounds showed toxicity against normal cells. A larger program of investigations will be launched to investigate the real potential interest of such compounds in anticancer applications.