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Cytotoxic activities and metabolic studies of new combretastatin analogues

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Macé, Yohan [UCL] Bony, Emilie [UCL] Delvaux, David [UCL] Pinto Fernandez, Adan [UCL] Mathieu, Véronique [ULB] Feron, Olivier [UCL] Quetin-Leclercq, Joëlle [UCL] Riant, Olivier [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès mixte
Publication date 2015
Language Anglais
Journal information "Medicinal Chemistry Research" - Vol. 24, no. 8, p. 3143-3156 (2015)
Peer reviewed yes
Publisher Springer ((United States) New York, NY)
issn 1054-2523
e-issn 1554-8120
Publication status Publié
Affiliations UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique
UCL - SST/IMCN/MOST - Molecules, Solids and Reactivity
UCL - SSS/LDRI - Louvain Drug Research Institute
UCL - SSS/IREC - Institut de recherche expérimentale et clinique
Keywords Benzofuroxan derivates ; Benzothiadiazole ; Cytotoxicity ; Metabolism ; Stilbenes
Links
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Bibliographic reference Macé, Yohan ; Bony, Emilie ; Delvaux, David ; Pinto Fernandez, Adan ; Mathieu, Véronique ; et. al. Cytotoxic activities and metabolic studies of new combretastatin analogues. In: Medicinal Chemistry Research, Vol. 24, no. 8, p. 3143-3156 (2015)
Permanent URL http://hdl.handle.net/2078.1/158627