Plasmepsin II inhibitory potential of phytochemicals isolated from African antimalarial plants: a computational approach.

Plamepsin II has been identified as a therapeutic target in the Plasmodium falciparum's life cycle and may lead to a drastic reduction in deaths caused by malaria worldwide. Africa flora is rich in medicinal qualities and possesses both simple and complex bioactive phytochemicals. This study utilized computational approaches like molecular docking, molecular dynamics simulation, quantum chemical calculations and ADMET to evaluate the plasmepsin II inhibitory properties of phytochemicals isolated from African antimalarial plants. Molecular docking was carried out to estimate the binding affinity of 229 phytochemicals whereby ekeberin A, dichamanetin, 10-hydroxyusambaresine, chamuvaritin and diuvaretin were selected. Further, RMSD and RMSF plots from the 100 ns simulation results showed that the screened phytochemicals were stable in the enzyme's binding pocket. The quantum chemical calculation revealed that all the phytochemicals are strong electrophiles, while ekeberin A was identified as the most stable and dichamanetin as the most reactive. Also, ADMET studies established the drug candidacy of the phytochemicals. Thus, these phytochemicals could act as good antimalarial agents after extensive in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.

LC-MS Analysis, Computational Investigation, and Antimalarial Studies of Azadirachta indica Fruit.

Malaria is a deadly disease that continues to pose a threat to children and maternal well-being. This study was designed to identify the chemical constituents in the ethanolic fruit extract of Azadirachta indica, elucidate the pharmacological potentials of identified phytochemicals through the density functional theory method and carry out the antimalarial activity of extract using chemosuppression and curative models. The liquid chromatography-mass spectrometry (LC-MS) analysis of the ethanolic extract was carried out, followed by the density functional theory studies of the identified phytochemicals using B3LYP and 6-31G (d, p) basis set. The antimalarial assays were performed using the chemosuppression (4 days) and curative models. The LC-MS fingerprint of the extract led to the identification of desacetylnimbinolide, nimbidiol, O-methylazadironolide, nimbidic acid, and desfurano-6α-hydroxyazadiradione. Also, the frontier molecular orbital properties, molecular electrostatic potential, and dipole moment studies revealed the identified phytochemicals as possible antimalarial agents. The ethanolic extract of A indica fruit gave 83% suppression at 800 mg/kg, while 84% parasitaemia clearance was obtained in the curative study. The study provided information about the phytochemicals and background pharmacological evidences of the antimalarial ethnomedicinal claim of A indica fruit. Thus, isolation and structure elucidation of the identified phytochemicals from the active ethanolic extract and extensive antimalarial studies towards the discovery of new therapeutic agents is recommended for further studies.

Revealing the Acetylcholinesterase Inhibitory Potential of Phyllanthus amarus and Its Phytoconstituents: In Vitro and in Silico Approach.

The inhibition of acetylcholinesterase plays a vital role in the treatment of Alzheimer disease. This study aimed to explore the acetylcholinesterase inhibition potential of Phyllanthus amarus and its phytoconstituents through an in vitro and in silico approach. The in vitro acetylcholinesterase inhibitory activity of P amarus was carried out, followed by the molecular docking studies of its phytoconstituents. The top-ranked molecules identified through molecular docking were subjected to molecular dynamics simulation (MDS) and density functional theory (DFT) studies. The results obtained revealed the methanolic extract of P amarus as a potent acetylcholinesterase inhibitor, while amarosterol A, hinokinin, ß-sitosterol, stigmasterol and ellagic acid were identified as potential acetylcholinesterase inhibitors. The MDS and DFT results are in agreement with those obtained from the docking studies. Our findings suggest further studies on the hit molecules.