Tyrosol Derivatives, Bearing 3,5-Disubstituted Isoxazole and 1,4-Disubstituted Triazole, as Potential Antileukemia Agents by Promoting Apoptosis.
Zaineb Abdelkafi-KoubaaImen AissaHichem Ben JannetNajet Srairi-AbidNaziha MarrakchiSamia MenifPublished in: Molecules (Basel, Switzerland) (2022)
In the present study, we assess tyrosol derivatives bearing 3,5-disubstituted isoxazoles and 1,4-disubstituted triazoles for their ability to inhibit the proliferation of K562 cells derived from leukemia as well as primary chronic myeloid leukemia (CML) cells obtained from the peripheral blood of 15 CML patients including 10 patients with untreated chronic phase and 5 patients with resistance against imatinib or multiple TKI. Our results showed that most derivatives displayed significant anti-proliferative activity against K562 cells in a dose-dependent manner. Among them, compounds 3d and 4a exhibited greater potent anticancer activity with respective IC 50 values of 16 and 18 µg/mL (45 µM and 61 µM). Interestingly, compound 3d inhibited CML cell proliferation not only in newly diagnosed but also in imatinib-resistant patients. We demonstrated that the anti-proliferative effect of this compound is mediated by a pro-apoptotic activity by promoting oxidative stress and modulating the activity of the Akt, p38 MAPK and Erk 1/2 pathways. In conclusion, our data highlight the potential of this class of derivative as a novel promising therapeutic agent for CML therapy.
Keyphrases
- chronic myeloid leukemia
- newly diagnosed
- induced apoptosis
- cell cycle arrest
- oxidative stress
- signaling pathway
- cell proliferation
- cell death
- end stage renal disease
- pi k akt
- ejection fraction
- peripheral blood
- peritoneal dialysis
- prognostic factors
- dna damage
- anti inflammatory
- bone marrow
- machine learning
- big data
- mesenchymal stem cells
- tyrosine kinase
- advanced non small cell lung cancer