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Novel derivatives of deoxycholic acid bearing aliphatic or cyclic diamine moieties at the C-3 position: Synthesis and evaluation of anti-proliferative activity |
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| Authors: | Irina I. Popadyuk Andrey V. Markov Valeriya O. Babich Oksana V. Salomatina Evgeniya B. Logashenko Marina A. Zenkova Nariman F. Salakhutdinov |
| Affiliation: | 1. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, 9, Lavrent’ev ave., Novosibirsk 630090, Russian Federation;2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, 8, Lavrent’ev ave., Novosibirsk 630090, Russian Federation;3. Novosibirsk State University, 2, Pirogova Str., Novosibirsk 630090, Russian Federation |
| Abstract: | A new library of deoxycholic acid derivatives bearing nitrogen-containing moieties at the C-3 position was synthesised from epoxy derivative 1 via an epoxide ring-opening reaction promoted by aliphatic or cyclic diamines and fully characterised by NMR and mass-spectroscopy. The synthesised compounds were screened for cytotoxicity against four human tumour cell lines. The results showed that some of the novel diamine-bearing derivatives displayed improved anti-proliferative activities over the parent compound DCA. Among them, a 1-methylpiperazine containing compound (6) showed promising activity and the highest selectivity against tumour cells of enterohepatic origin (HepG2: IC50 = 3.6 µM, SI = 9.0; HuTu-80: IC50 = 4.6 µM, SI = 6.9) and was identified as a lead molecule. |
| Keywords: | Deoxycholic acid derivatives Epoxides Diamines Cytotoxicity Anti-proliferative activity |
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