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

Abstract

AbstractAmmonium 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 μg/mL) and inhibitory concentration IC50 values in the low micromolar range of 171.062, 189.803, 195.469 and 181.272 μg/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.