A Facile One-Pot Solvent-Free Synthesis, in Vitro and in Silico Studies of a Series of Tetrahydropyridine Derivatives as Breast Cancer Inhibitors

Ammonium trifluoroacetate (ATA) catalysed synthesis of 1,2,5,6-tetrahydropyridine (THP) derivatives, under eco-friendly conditions via a facile one-pot strategy. We have synthesized fifteen THP derivatives, and docked into the crystal structure of Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN) tumour suppressor protein (PDB ID: 1D5R) based on drug-likeness prediction and pharmacokinetic properties. Molecular docking simulation studies reveal that four of our synthesised compounds are potential hit candidates because they bound to the receptor through 5-7 conventional hydrogen bonds with -9.7 to -8.6 kcal/mol of binding energy. The compounds were evaluated using the in vitro inhibitory activity of MCF-7 breast cancer cell lines. Identified hit compounds showed moderate inhibition at (160-320 mu g/mL) and inhibitory concentration IC50 values in the low micromolar range of 171.062, 189.803, 195.469 and 181.272 mu g/mL respectively. The results obtained are very promising; therefore fine-tuning the substituents of hit molecules with appropriate bioisosteres can lead to the development of potential leads. Ammonium trifluoroacetate (ATA) catalysed synthesis of 1,2,5,6-tetrahydropyridine (THP) derivatives, under eco-friendly conditions via a facile one-pot strategy has been repoted. Molecular docking simulation studies followed by in vitro inhibitory activity of MCF-7 breast cancer cell lines for the synthesized THP derivatives were performed and the studies reveal that four of the fifteen synthesised compounds are found as potential hit candidates.image

Automated summary

Ammonium trifluoroacetate (ATA) catalysed synthesis of 1,2,5,6-tetrahydropyridine (THP) derivatives under eco-friendly conditions using a facile one-pot strategy is reported. Molecular docking simulation and in vitro inhibitory activity evaluation on MCF-7 breast cancer cell lines identified four potential hit candidates among the synthesized compounds. These compounds hold promise as potential lead molecules.