ABSTRACT
In vitro acetylcholinesterase activities of the hexane, dichloromethane, ethyl acetate, n-butanol and aqueous extracts of leaves of Ocotea percoriacea Kosterm. (Lauraceae) were evaluated. The bioguided fractionation of the most active extract (dichloromethane) using silica gel open-column chromatography led to an active alkaloidal fraction composed of isocorydine N-oxide, isocorydine N-oxide derivative, palmatine, roemerine and roemerine N-Oxide. The identification of the chemical structure of these compounds was carried out with high-performance liquid chromatography coupled to electrospray ionization multiple-stage mass spectrometry (HPLC-ESI-MS/MS). Aiming to understand their inhibitory activities, these alkaloids were docked into a 3D model of Electrophorus electricus Acetylcholinesterase (EelAChE) built in the Modeller 9.18 employing homology modeling approach. The results suggest that the alkaloids had the same binding mode and, possibly, the inhibition mechanism of classic drugs (ex. tacrine and donepezil). The structural difference of these compounds opens a new opportunity for the optimization of leading compounds.
Subject(s)
Acetylcholinesterase/metabolism , Alkaloids/pharmacology , Cholinesterase Inhibitors/pharmacology , Models, Molecular , Ocotea/chemistry , Plant Extracts/pharmacology , Alkaloids/chemistry , Alkaloids/isolation & purification , Animals , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/isolation & purification , Chromatography, High Pressure Liquid , Electrophorus , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves/chemistry , Tandem Mass SpectrometryABSTRACT
The new alkene lactone, (3E)-5,6-dihydro-5-(hydroxymethyl)-3-docdecylidenefuran-3(4H)-one (1), named majoranolide B, and three alkene lactones known as majorenolide (2), majoranolide (3) and majorynolide (4) were obtained from the aerial parts of Persea fulva (Lauraceae). The structures were elucidated in light of extensive spectroscopic analysis, including 1D, 2D NMR (1H, 13C, 1H-1H-COSY, HMBC and HSQC) and HR-ESI-MS. These compounds were screened for their in vitro antiproliferative activity in rat C6 glioma and astrocyte cells using MTT assay and in silico by molecular docking against targets that play a central role in controlling glioma cell cycle progression. Majoranolide (3) is the most active compound with IC50 6.69⯵M against C6 glioma cells, followed by the compounds 1 (IC50 9.06⯵M), 2 (IC50 12.04⯵M) and 4 (IC50 41.90⯵M). The alkene lactones 1-3 exhibited lower toxicity in non-tumor cells when compared to glioma cells. Molecular docking results showed that majoranolide establishes hydrogen bonds with all targets through its α,ß-unsaturated-γ-lactone moiety, whereas the long-chain alkyl group binds by means of several hydrophobic bonds. In the present study, it can be concluded from the anti-proliferative activity of isolates against C6 glioma cells that lactone constituents from P. fulva could have a great potential for the control of C6 glioma cells.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Lactones/pharmacology , Lauraceae/chemistry , Molecular Docking Simulation , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Lactones/chemistry , Lactones/isolation & purification , Molecular Structure , Plant Leaves/chemistry , Rats , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Este trabalho apresenta o estudo morfoanatômico das folhas e caules de Microlicia hatschbachii Wurdack, Melastomataceae. Esta espécie possui folhas elípticas a oval-elípticas, margem inteira, ápice agudo e base simétrica e arredondada. A lâmina foliar é anfiestomática, com estômatos do tipo anisocítico e anomocítico, a epiderme é uniestratificada, com células isodiamétricas em secção transversal, e presença de inúmeros tricomas glandulares. O mesofilo é do tipo isobilateral com feixe vascular bicolateral envolvido por algumas células esclerenquimáticas na nervura central. O caule tem secção quadrangular a circular e epiderme unisseriada, com tricomas similares aos da folha. Drusas de oxalato de cálcio foram encontradas nas folhas e no caule.
This work shows the morpho-anatomical study of leaf and stem of Microlicia hatschbachii Wurdack (Melastomataceae). Its leaves are elliptic to oval-elliptic, with entire margin, acute apex and rounded symmetrical base. The leaf blade is amphistomatical with anisocytic and anomocytic stomata, in transection the epidermis is uniseriate with isodiametric cells and presence of several glandular trichomes. The mesophyll is isobilateral with bicollateral vascular bundles surrounded by some sclerenchymatic cells in midrib. The stem has a quadrangular to circular transection and uniseriate epidermis with trichomes like ones of leaf. Several druses of calcium oxalate are found in the leaf and stem.