Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments

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...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Ferenczi Etelka
Keglevich Péter
Tayeb Bizhar Ahmed
Minorics Renáta
Papp Dávid
Schlosser Gitta
Zupkó István
Hazai László
Csámpai Antal
Dokumentumtípus: Cikk
Megjelent: 2024
Sorozat:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 25 No. 13
doi:10.3390/ijms25137428

mtmt:35087983
Online Access:http://publicatio.bibl.u-szeged.hu/39770
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520 3 |a 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. 
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700 0 1 |a Tayeb Bizhar Ahmed  |e aut 
700 0 1 |a Minorics Renáta  |e aut 
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700 0 1 |a Schlosser Gitta  |e aut 
700 0 1 |a Zupkó István  |e aut 
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