Details

Autor(en) / Beteiligte

• Othman, Esraa M.
• Fayed, Eman A.
• Husseiny, Ebtehal M.
• Abulkhair, Hamada S.

Titel

Apoptosis induction, PARP-1 inhibition, and cell cycle analysis of leukemia cancer cells treated with novel synthetic 1,2,3-triazole-chalcone conjugates

Ist Teil von

• Bioorganic chemistry, 2022-06, Vol.123, p.105762-105762, Article 105762

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •A novel series of 1,2,3-triazoles bearing chalcone fragments was designed, synthesized.•The cytotoxic activity of the synthesized compounds was evaluated against sixty human cancer cell lines.•Leukemia cancer cell lines were the most sensitive toward the effect of newly designed compounds.•Compounds 11b, 11e, 11h, and 11j exerted the most potent cytotoxic activity.•Compound 11e further evaluated for its apoptosis induction and PARP-1 inhibition potential. Leukemia is a life-threatening nonepithelial malignant disorder that is characterized by uncontrolled growth of the hematopoietic cells. To date, there are still unmet needs for effective and less toxic medication for the management of this malignant tumor. Here, we report the synthesis of a new set of suggested anticancer molecules by joining the 1,2,3-triazole and chalcone privileged fragments in one scaffold to develop novel candidates in leukemia therapy. All the synthesized compounds have been screened for their cytotoxicity effect against a panel of 60 cancer cell lines at the National Cancer Institute. The leukemia cancer cells were found to be the most sensitive toward the effect of new molecules. A subsequent set of in vitro biological evaluation studies has been conducted on the most promising derivatives to identify their effect on such a cancer type. Four derivatives (11b, 11e, 11h, and 11j) showed excellent anticancer activity in the RPMI-8226 cells with IC50 values at low micromolar concentrations. Among these compounds, 11e was the most effective with an IC50 value of 3.17 µM (32-folds stronger than Staurosporine). The potential mechanistic effect of the latter has been further studied through the investigation of its potential effect on the cell cycle, PARP-1, and certain apoptotic and anti-apoptotic markers in the RPMI-8226 cells. Results of those studies revealed the potential of 11e to induce apoptosis through the upregulation of BAX, caspase-3, and caspase-9, and to arrest the cell cycle at the S phase.