Synthesis and Biological Evaluation of (-) and (+)-Spiroleucettadine and Analogues.
Michael P BadartEmma M BarnesAndrew P CordingSelena C L GilmerIan D BillinghurstVeera V Shivaji R EdupugantiGuillaume LesseneAbigail R BlandRebekah L BowerZohaib RanaScott A FergusonHelen K Opel ReadingGregory M CookRhonda J RosengrenKurt L KrauseAllan B GambleJohn C AshtonBill C HawkinsPublished in: ChemMedChem (2021)
A second-generation enantiospecific synthesis of spiroleucettadine is described. The original reported antibacterial activity was not observed when the experiment was repeated on the synthetic samples; however, significant anti-proliferative activity was uncovered for both enantiomers of spiroleucettadine. Comparison of the optical rotational data and ORD-CD spectra of both enantiomers and the reported spectrum from the natural source have not provided a definitive answer regarding the absolute stereochemistry of naturally occurring spiroleucettadine. Efforts then focussed on alteration at the C-4 and C-5 positions of the slightly more active (-)-spiroleucettadine. Ten analogues were synthesised, with three analogues found to possess similar anti-proliferative profiles to spiroleucettadine against the H522 lung cancer cell line.
Keyphrases
- molecular docking
- structure activity relationship
- high resolution
- capillary electrophoresis
- electronic health record
- high speed
- big data
- quality improvement
- locally advanced
- molecular dynamics simulations
- density functional theory
- mass spectrometry
- squamous cell carcinoma
- artificial intelligence
- molecular dynamics
- silver nanoparticles
- rectal cancer