Cytotoxic activities and metabolic studies of new combretastatin analogues

Macé, Yohan;Bony, Emilie;Delvaux, David;Pinto Fernandez, Adan;Riant, Olivier;et.al.
(2015) Medicinal Chemistry Research : an international journal for rapid communications on design and mechanisms of action of biologically active agents — Vol. 24, n° 8, p. 3143-3156 (2015)

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Authors
  • Macé, YohanUCLouvain
    Author
  • Bony, EmilieUCLouvain
    Author
  • Delvaux, DavidUCLouvain
    Author
  • Pinto Fernandez, AdanUCLouvain
    Author
  • Feron, Olivierorcid-logoUCLouvain
    Author
  • Quetin-Leclercq, JoëlleUCLouvain
    Author
  • Riant, OlivierUCLouvain
    Author
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Abstract
A new series of combretastatin analogues with B-ring modifications were synthesized and evaluated for their cytotoxicity against one endothelial (HUVEC) and three tumor cell lines, e.g., the LoVo colon, the PC-3 prostate, and the U373 glioma cancer models. These new combretastatin analogues showed differential cytotoxic activities, cis derivatives 13 5-(2-Z-trimethoxyphenylethenyl)- benzo[1,2-c]1,2,5-oxadiazole N1-oxide and 14 5-(2-Ztrimethoxyphenylethenyl) benzo[1,2,5]thiadiazole exhibiting interesting cytotoxicity both on endothelial and on tumor cells. Unlike the cis benzofurazan 12 5-(2-Ztrimethoxyphenylethenyl) benzo[1,2-c]1,2,5-oxadiazole, induction of apoptosis by 13 appeared to be through caspase-3 activation. Metabolic investigations showed a positive correlation between highly metabolized compounds and cytotoxic activity, suggesting that highly cytotoxic derivatives may act as pro-drug via a reductive metabolization to more active metabolites.
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Macé, Y., Bony, E., Delvaux, D., Pinto Fernandez, A., Mathieu, V., Kiss, R., Feron, O., Quetin-Leclercq, J., & Riant, O. (2015). Cytotoxic activities and metabolic studies of new combretastatin analogues. Medicinal Chemistry Research : an international journal for rapid communications on design and mechanisms of action of biologically active agents, 24(8), 3143-3156. https://doi.org/10.1007/s00044-015-1363-3 (Original work published 2015)