Novel derivatives of deoxycholic acid bearing aliphatic or cyclic diamine moieties at the C-3 position: Synthesis and evaluation of anti-proliferative activity
- Bioorg Med Chem Lett. 2017 Aug 15;27(16):3755-3759. doi: 10.1016/j.bmcl.2017.06.072.
- 1. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, 9, Lavrent'ev ave., Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
- 2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, 8, Lavrent'ev ave., Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
- 3. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, 8, Lavrent'ev ave., Novosibirsk 630090, Russian Federation; Novosibirsk State University, 2, Pirogova Str., Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
- 4. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, 9, Lavrent'ev ave., Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
- 5. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, 8, Lavrent'ev ave., Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
- 6. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, 8, Lavrent'ev ave., Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
- 7. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, 9, Lavrent'ev ave., Novosibirsk 630090, Russian Federation; Novosibirsk State University, 2, Pirogova Str., Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
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=3.6µM, SI=9.0; HuTu-80: IC50=4.6µM, SI=6.9) and was identified as a lead molecule.