Synthesis, characterization, computational, anticancer and anti-inflammatory studies of pregabalin esters and their complexes with heavy metals

Abstract

The current study entails a series of pregabalin ester complexed with zinc and copper; further characterized by spectroscopic techniques and biological assays. Docking analysis revealed three complexes with favorable binding interactions which were further subjected to in-vitro anti-inflammatory and anticancer activities. The complex-5 displayed most potent anti-inflammatory activity against Luminol-enhanced Chemiluminescence assay with IC50 value of 7.7 ± 0.8 µM as compared to standard Ibuprofen with IC50 value of 11.2 ± 1.9 µM; whereas none of them showed significant outcomes against HeLa cell lines for antiproliferative activity as compared with standard doxorubicin. Computational studies were carried out using the reported crystal structure of multidrug resistant Alpha2S protein (PDB-ID: 6ND9), neurokinin-1 receptor (PDB-ID: 2KSA) and dihydrofolate reductase (PDB-ID: 3GHW); indicating the compound 3 showed significant interactions at all receptors. As the analogues were more active than parent drug in some respects; therefore, the expansion of the project can be planned to carry out more pharmacological screening.