Synthesis of Nitrogen-Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells.
Matheus A MeirellesCarolyne B BragaCatia OrnelasRonaldo Aloise PilliPublished in: ChemMedChem (2019)
Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin chloroacrylamide 13 e displayed the lowest IC50 values for both MCF-7 (0.5 μm) and PC3 (0.3 μm) cells, about 26-fold more potent than goniothalamin (1). Besides its higher potency, compound 13 e also displayed much higher selectivity than goniothalamin. In contrast, goniothalamin isobutyramide 13 c was the most potent analogue against Caco-2 cells (IC50 =0.8 μm), about 10-fold more potent and 17-fold more selective than 1. These results reveal the potential of compounds 13 c and 13 e for further in vivo studies, representing the first goniothalamin analogues with IC50 values in the low micromolar range and high selectivity against MCF-7, Caco-2, and PC3 cancer cell lines.
Keyphrases
- induced apoptosis
- molecular docking
- papillary thyroid
- cell cycle arrest
- prostate cancer
- structure activity relationship
- squamous cell
- anti inflammatory
- magnetic resonance imaging
- magnetic resonance
- oxidative stress
- single cell
- lymph node metastasis
- climate change
- pi k akt
- molecular dynamics simulations
- dna methylation
- amino acid