MOLECULAR DOCKING-BASED PREDICTIONS OF ESTROGEN RECEPTOR-ALPHA BINDING AFFINITY OF COMMON PARABENS AND CORRELATION WITH HPLC DETERMINED PLASMA CONCENTRATIONS

Abstract

The Ni(II) and Co(II) complexes derived from 4-aminoantipyrine derivatives were synthesized and characterised by IR, Mass, 1H NMR, electronic spectra, magnetic moment, molar conductance, thermal analysis. The obtained analytical data shows the Novel Ni(II) and Co (II) complexes shows metal to ligand ratio 1:2. The ligand acts as bidentate ligand co-ordinated to central metal ion through azomethine nitrogen. The geometry of synthesized novel Ni(II) and Co(II) complexes were octahedral. The novel complexes were screened for their biological potential against selected strains of antibacterial and antifungal organism by broth dilution method. The molecular docking studies of Novel complexes against E. coli DNA Gyrase B (PDB ID: 6YD9) and Candida albicans lanosterol 14-α-demethylase (PDB ID: 5TZ1). The docking results demonstrate that the synthesized cobalt and nickel complexes exhibit consistently stronger affinity toward lanosterol 14-α-demethylase than toward DNA gyrase B, suggesting greater potential for antifungal activity.Endocrine disrupting properties have raised numerous concerns, and they have been investigated for their interactions with the estrogen receptor and their presence in biological systems. The present study was designed to assess the estrogen receptor alpha (ERα)-binding potential of four widely used Parabens (PBs) (Methylparaben (MePB), ethylparaben (EtPB), Propylparaben (PrPB), and Butylparaben (BuPB)) by molecular docking and to compare the docked result with in vivo plasma exposure data obtained from a validated HPLC method. Ligand structures were retrieved from the PubChem data base and then upload into SeamDock for docking with the human ERα ligand binding domain (PDB ID:1A52) using the AutoDock Vina scoring algorithm through the SeamDock platform. Docking affinities and interaction profiles were used to assess protein-ligand interactions. Simultaneously, the HPLC method was validated for chromatographic performance and plasma quantification of PBs. Based on the molecular docking results, PrPB showed the highest binding affinity towards the ERα, followed y EtPB, BuPB, and MePB with binding energies of -5.5, -5.2, -5.1, and -3.7 kcal/mol, respectively. Multiple hydrogen-bonding and hydrophobic interactions were found to be important in the stabilization of the receptor-protein interaction by employing the protein-ligand interaction analysis. The HPLC method showed excellent analytical performance with the recovery of 98.83% to 99.85%, theoretical plate numbers of 8219 and 8989, and correlation coefficient values of 0.9927-0.9992, which indicated good performance for the analysis of PBs. Overall, the analytical and computational results suggest that structural differences in PBs greatly affect the binding affinity of ERα. PrPB was found to have the highest predicted estrogen receptor-binding potential among the compounds investigated. The combination of HPLC with molecular docking is a useful platform for assessing potential endocrine disrupting effects of common parabens and can be used as a tool for future exposure risk assessment.