Betulinic acid derived hydroxamates and betulin derived carbamates are interesting scaffolds for the synthesis of novel cytotoxic compounds.

Published on Dec 1, 2015in European Journal of Medicinal Chemistry6.514
· DOI :10.1016/J.EJMECH.2015.10.043
Jana Wiemann9
Estimated H-index: 9
(MLU: Martin Luther University of Halle-Wittenberg),
Lucie Heller14
Estimated H-index: 14
(MLU: Martin Luther University of Halle-Wittenberg)
+ 3 AuthorsRené Csuk28
Estimated H-index: 28
(MLU: Martin Luther University of Halle-Wittenberg)
Sources
Abstract
Abstract The betulinic acid-derived hydroxamates 5 – 18 , the amides 19 – 24 , and betulin-derived bis-carbamates 25 – 28 as well as the carbamates 31 – 40 and 44 – 48 were prepared and evaluated for their antiproliferative activity in a photometric sulforhodamine B (SRB) assay against several human cancer cell lines and nonmalignant mouse fibroblasts (NIH 3T3). While for 3- O -acetyl hydroxamic acid 5 EC 50 values as low as EC 50  = 1.3 μM were found, N , O -bis-alkyl substituted hydroxamates showed lowered cytotoxicity (EC 50  = 16–20 μM). In general, hydroxamic acid derivatives showed only reduced selectivity for tumor cells, except for allyl substituted compound 13 (EC 50  = 5.9 μM for A2780 human ovarian carcinoma cells and EC 50  > 30 μM for nonmalignant mouse fibroblasts). The cytotoxicity of betulinic acid derived amides 19 – 24 and of betulin derived bis-carbamates 25 – 28 was low, except for N -ethyl substituted 25 . Hexyl substituted 39 showed EC 50  = 5.6 μM (518A2 cells) while for mouse fibroblasts EC 50  > 30 was determined.
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Methyl triterpenoates derived from oleanolic, ursolic, betulinic, glycyrrhetinic, platanic, or maslinic acid were converted into their corresponding sulfamates and carbamoylsulfamates. The sulfamates were screened in photometric sulforhodamine assays for cytotoxic activity employing several human tumor cell lines. Many of the compounds showed EC50 values in one-digit μM concentration. Of special interest seems methyl (3β) 3-(aminosulfonyloxy)-11-oxo-oleanoate (18) showing good cytotoxicity for t...
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Betulinic acid (BA), a natural compound with a lupan skeleton, has been highly investigated in the past decade for a plethora of beneficial properties, including anti-cancer, anti-inflammatory, anti-angiogenic, immune-modulatory, and anti-HIV effects. In particular, BA has been reported to be effective in vitro against tumor cell lines of different origins, and also in vivo, in animal models of cancer. The best characterized mechanism of its antitumor effect consists of triggering apoptosis via ...
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