Antimalarial potential, LC-MS secondary metabolite profiling and computational studies of Zingiber officinale.

Malaria is among the top-ranked parasitic diseases that pose a threat to the existence of the human race. This study evaluated the antimalarial effect of the rhizome of Zingiber officinale in infected mice, performed secondary metabolite profiling and detailed computational antimalarial evaluation through molecular docking, molecular dynamics (MD) simulation and density functional theory methods. The antimalarial potential of Z. officinale was performed using the in vivo chemosuppressive model; secondary metabolite profiling was carried out using liquid chromatography-mass spectrometry (LC-MS). Molecular docking was performed with Autodock Vina while the MD simulation was performed with Schrodinger desmond suite for 100 ns and DFT calculations with B3LYP (6-31G) basis set. The extract showed 64% parasitaemia suppression, with a dose-dependent increase in activity up to 200 mg/kg. The chemical profiling of the extract tentatively identified eight phytochemicals. The molecular docking studies with plasmepsin II and Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) identified gingerenone A as the hit molecule, and MMGBSA values corroborate the binding energies obtained. The electronic parameters of gingerenone A revealed its significant antimalarial potential. The antimalarial activity elicited by the extract of Z. officinale and the bioactive chemical constituent supports its usage in ethnomedicine.Communicated by Ramaswamy H. Sarma.

Investigating the multitargeted anti-diabetic potential of cucurbitane-type triterpenoid from Momordica charantia: an LC-MS, docking-based MM\GBSA and MD simulation study.

Type 2 diabetes accounts for the largest percentage of all diabetic cases worldwide. Cucurbitane-type triterpenes are mainly found in Momordica charantia and possess excellent pharmacological activities. This study was designed to identify cucurbitane-type triterpene from Momordica charantia using Liquid Chromatography-Mass Spectrometry (LC-MS) analysis, examine its anti-diabetic property with molecular docking against diabetes enzymes (alpha-amylase, alpha-glucosidase, dipeptidyl dipeptidase IV and peroxisome proliferator-activated receptor gamma). The stability and interactions of the docked complexes were investigated using molecular dynamics simulation, while the pharmacokinetic and toxicity profile of the ligand was examined using an ADMET server. (23E)-Cucurbita-5,23,25-triene-3,7-dione (CUB) was identified from the LC-MS profiling of the methanolic extract of M. charantia. The molecular docking studies showed that the identified phytochemical elicited good binding energy against all the target receptors. The RMSD and RMSF plots obtained from the 100 ns molecular dynamics simulation showed that the ligand was stable and established substantial interactions with the amino acid residues of the diabetes enzymes which were confirmed by the MM\GBSA computations. The pharmacokinetic and toxicity properties of the ligand showed it was safer as an anti-diabetic drug candidate. Extensive isolation, in vitro and in vivo studies of the ligand against the diabetic enzymes is recommended.Communicated by Ramaswamy H. Sarma.

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.