Identification of novel peptide inhibitors of Plasmodium falciparum dihydrofolate reductase (PfDHFR): molecular docking and MD simulation studies.

The presence of drug-resistant variants of Plasmodium parasites within the population has presented a substantial obstacle to the eradication of Malaria. As a result, numerous research groups have directed their efforts towards creating new medication candidates that specifically target parasites. In this study, our main objective was to identify tri-peptide inhibitors for Plasmodium falciparum Dihydrofolate Reductase (PfDHFR) with the aim of finding a new peptide that exhibits superior binding properties compared to the current inhibitor, WR99210. In order to achieve this objective, a virtual library consisting of 8000 tripeptides was generated and subjected to computational screening against wild-type PfDHFR. The purpose of this screening was to discover the most effective binders at the active site. The four most optimal tripeptides identified (Trp-Trp-Glu, Trp-Phe-Tyr, Phe-Trp-Trp, Tyr-Trp-Trp) exhibited significant non-covalent interactions inside the active site of PfDHFR and had binding energies ranging from -9.5 to -9.0 kcal/mol and WR99210 had a binding energy of -6.2 kcal/mol. A 250 ns Molecular Dynamics (MD) simulation was performed to investigate the kinetic and thermodynamic characteristics of the protein-ligand complexes. The Root Mean Square Deviation (RMSD) values for the optimal tripeptides fell within the allowed range, indicating the stability of the ligands inside the protein complex. The Ki value for the most effective tripeptide was 0.3482 µM, whereas WR99210 had a Ki value of 1.02 µM. This article presents the initial discovery of peptide inhibitors targeting PfDHFR. In this text, we provide a comprehensive explanation of the interactions that occur between peptides and the enzyme.Communicated by Ramaswamy H. Sarma.

Chemical profiling and α-glucosidase inhibitory activity of essential oils extracted with two methods from some North Western Himalayan aromatic crops.

Solvent-free hydrodistillation adsorption apparatus (HDA) and normal clevenger hydrodistillation (NC) were applied to obtain Juniperus communis, Valeriana jatamansi and Hedychium spicatum essential oils (EOs). The yields, chemical compositions and α-glucosidase inhibitory activity of the EOs were investigated. Obtained EOs were analyzed using gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) instruments. Recovery improvement was observed in HDA method (30.4%, 27.3% and 29.0% more recovery of EOs than NC method for V. jatamansi, H. spicatum and J. communis, respectively). Present results demonstrated NCV (V. jatamansi EO (essential oil) by NC method) had highest α-glucosidase inhibitory activity with half-maximal inhibitory concentration (IC50) values of 8.20 µg/mL. As a result, HDA method is considered to be the promising theme for producing EOs with high production recovery. Furthermore, current findings demonstrated that the selected EOs may be a good natural antidiabetic.

WITHDRAWN: PEGylated hemoglobin: Role of surface configuration of PEG for the modulation of hemoglobin vasoactivity.

This paper has been withdrawn since all of the coauthors had not approved of its submission.