Ferenczi, E.; Keglevich, P.; Tayeb, B.A.; Minorics, R.; Papp, D.; Schlosser, G.; Zupkó, I.; Hazai, L.; Csámpai, A. Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments. Int. J. Mol. Sci.2024, 25, 7428.
Ferenczi, E.; Keglevich, P.; Tayeb, B.A.; Minorics, R.; Papp, D.; Schlosser, G.; Zupkó, I.; Hazai, L.; Csámpai, A. Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments. Int. J. Mol. Sci. 2024, 25, 7428.
Ferenczi, E.; Keglevich, P.; Tayeb, B.A.; Minorics, R.; Papp, D.; Schlosser, G.; Zupkó, I.; Hazai, L.; Csámpai, A. Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments. Int. J. Mol. Sci.2024, 25, 7428.
Ferenczi, E.; Keglevich, P.; Tayeb, B.A.; Minorics, R.; Papp, D.; Schlosser, G.; Zupkó, I.; Hazai, L.; Csámpai, A. Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments. Int. J. Mol. Sci. 2024, 25, 7428.
Abstract
In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone units, were evaluated for their antiproliferative activity on malignant cell lines MDA-MB-231 (triple negative breast cancer), A2780 (ovarian cancer), HeLa (human cervical cancer) and SH-SY5Y (neuroblastoma) as well as human embryonal lung fibroblast MRC-5 served as reference non-malignant cell line for the assessment of the therapeutic window of the tested hybrids. The biological assays identified a trimethoxyphenyl-containing chalcone-vindoline hybrid (36) as a promising lead compound exhibiting submicromolar activity on A2780 cells with a marked therapeutic window. These results suggest that ovarian cancer might be considered as a prioritized target of treatment with 36.
Medicine and Pharmacology, Oncology and Oncogenics
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