Antiangiogenic Tocotrienol Derivatives from <i>Garcinia amplexicaulis</i>

Phytochemical investigation of a dichloromethane extract from <i>Garcinia amplexicaulis</i> stem bark led to the isolation of four new tocotrienols (<b>1</b>–<b>4</b>); two known tocotrienols, two triterpenes, and a xanthone were also isolated. Their structures were mainly established using NMR and MS methods. The main compounds isolated, δ-amplexichromanol (<b>1</b>) and γ-amplexichromanol (<b>2</b>), were evaluated on VEGF-induced angiogenesis using a Matrigel assay. Compounds <b>1</b> and <b>2</b> inhibited in vitro angiogenesis of VEGF-induced human primary endothelial cells in the low nanomolar range. Their capacity to inhibit VEGF-induced proliferation of endothelial cells partially explained this activity, although δ-amplexichromanol (<b>1</b>) also prevented adhesion and migration processes

Trigocherrin A, the First Natural Chlorinated Daphnane Diterpene Orthoester from <i>Trigonostemon cherrieri</i>

Trigocherrin A, a chlorinated and highly oxygenated daphnane diterpenoid orthoester (DDO), was isolated from the bark of <i>Trigonostemon cherrieri</i>. Trigocherrin A is the first example of a naturally occurring halogenated DDO. Its structure was elucidated by comprehensive analysis of NMR spectroscopic data, and its absolute configuration was determined by comparison of experimental and theoretically calculated ECD spectra. Trigocherrin A exhibited a potent and selective effect against Chikungunya virus in Vero cells

Prostratin and 12‑<i>O</i>‑Tetradecanoylphorbol 13-Acetate Are Potent and Selective Inhibitors of Chikungunya Virus Replication

A chemical study of the Vietnamese plant species <i>Trigonostemon howii</i> led to the isolation of a new tigliane-type diterpenoid, trigowiin A (<b>1</b>), along with several known coumarins and phenylpropanoids. The planar structure and the relative configuration of compound <b>1</b> were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Trigowiin A (<b>1</b>) exhibited moderate antiviral activity in a virus-cell-based assay for Chikungunya virus (CHIKV). Since the structure of compound <b>1</b> is closely related to those of well-known tigliane diterpenoids such as prostratin (<b>2</b>), phorbol (<b>3</b>), 12-<i>O</i>-tetradecanoylphorbol 13-acetate (TPA) (<b>4</b>), and 4α-TPA (<b>5</b>), the antiviral activity of the latter compounds was also evaluated against CHIKV, as well as in virus-cell-based assays of two additional members of the genus <i>Alphavirus</i> (Sindbis virus, SINV, and Semliki forest virus, SFV). Whereas prostratin inhibited CHIKV replication with a moderate EC₅₀ of 2.6 μM and a selectivity index (SI) approximating 30, compound <b>4</b> proved to be an extremely potent inhibitor, with an EC₅₀ of ∼3 nM and a SI near 2000. Interestingly, no or very little activity was observed on the replication of SINV and SFV

Trigocherrin A, the First Natural Chlorinated Daphnane Diterpene Orthoester from <i>Trigonostemon cherrieri</i>

Trigocherrin A, a chlorinated and highly oxygenated daphnane diterpenoid orthoester (DDO), was isolated from the bark of <i>Trigonostemon cherrieri</i>. Trigocherrin A is the first example of a naturally occurring halogenated DDO. Its structure was elucidated by comprehensive analysis of NMR spectroscopic data, and its absolute configuration was determined by comparison of experimental and theoretically calculated ECD spectra. Trigocherrin A exhibited a potent and selective effect against Chikungunya virus in Vero cells

Evaluation of Green Corrosion Inhibition by Alkaloid Extracts of <i>Ochrosia oppositifolia</i> and Isoreserpiline against Mild Steel in 1 M HCl Medium

Alkaloid extracts of leaves (OOL) and bark (OOB) of <i>Ochrosia oppositifolia</i>, as well as isoreserpiline (ISR), the major alkaloid isolated from OOL and OOB, were investigated as potential corrosion inhibitors for mild steel (MS) in 1 M HCl medium. The inhibition properties of these phytoconstituents were studied using electrochemical techniques (potentiodynamic polarization measurements and electrochemical impedance spectroscopy, EIS) and scanning electron microscopy (SEM). The results indicated that these green inhibitors effectively reduced the corrosion rate. Polarization studies showed that these inhibitors decreased the corrosion current densities by a mixed-mode mechanism. The EIS data were analyzed by an equivalent circuit model for the electrode/electrolyte interface. SEM observations confirmed the existence of an adsorbed protective film of green inhibitors, and the adsorption was found to follow the Langmuir adsorption isotherm. FTIR and molecular modeling studies were also employed and revealed that the presence of ISR could be responsible for the corrosion inhibition potential of OOL and OOB

Goniomedines A and B: Unprecedented Bisindole Alkaloids Formed through Fusion of Two Indole Moieties via a Dihydropyran Unit

Two novel bisindole alkaloids, goniomedines A (<b>1</b>) and B (<b>2</b>), possessing an unprecedented quebrachamine–pleioarpamine-type skeleton, in which indole moieties are fused via a dihydropyran unit, were isolated from the stem bark of <i>Gonioma malagasy.</i> The structures were elucidated by comprehensive analysis of MS and NMR spectroscopic data. Their absolute configurations were deduced following the comparison of experimental and theoretically calculated ECD spectra and through biogenetic considerations. Goniomedine B (<b>2</b>) exhibited moderate activity against <i>Plasmodium falciparum</i>

Anacardic Acids from <i>Knema hookeriana</i> as Modulators of Bcl-xL/Bak and Mcl-1/Bid Interactions

Proteins of the Bcl-2 family are key targets in anticancer drug discovery. Disrupting the interaction between anti- and pro-apoptotic members of this protein family was the approach chosen in this study to restore apoptosis. Thus, a biological screening on the modulation of the Bcl-xL/Bak and Mcl-1/Bid interactions permitted the selection of <i>Knema hookeriana</i> for further phytochemical investigations. The ethyl acetate extract from the stem bark led to the isolation of six new compounds, three acetophenone derivatives (<b>1</b>–<b>3</b>) and three anacardic acid derivatives (<b>4</b>–<b>6</b>), along with four known anacardic acids (<b>7</b>–<b>10</b>) and two cardanols (<b>11</b>, <b>12</b>). Their structures were elucidated by 1D and 2D NMR analysis in combination with HRMS experiments. The ability of these compounds to antagonize Bcl-xL/Bak and Mcl-1/Bid association was determined, using a protein–protein interaction assay, but only anacardic acid derivatives (<b>4</b>–<b>10</b>) exhibited significant binding properties, with <i>K</i>_i values ranging from 0.2 to 18 μM. Protein–ligand NMR experiments further revealed that anacardic acid <b>9</b>, the most active compound, does not interact with the anti-apoptotic proteins Bcl-xL and Mcl-1 but instead interacts with pro-apoptotic protein Bid

Effect of the cycloartane on HT-29 cell death (apoptosis and necrosis) and cell cycle progression.

<p>(A) Percentage of cells showing phosphatidylserine translocation, as measured by cell-surface annexin V binding and free PI: cells negative for annexin V and positive for PI are necrotic (Q1); cells positive for both annexin V and PI are in late apoptosis (Q2); cells negative for both annexin V and PI (Q3) are viable cells; and cells positive for annexin V and negative for PI are in early apoptosis (Q4). Cells were incubated for 24 hours with 0.1% v/v DMSO₄ (vehicle control) or the cycloartane at concentrations of 12.5, 25, or 50 μM, as indicated. (B) Flow cytometry histograms showing the distribution of cells in different phases of the cell cycle (G₁, S and G₂/M) at the beginning of the experiment (0 hr) and at 12, 24 and 48 hours of treatment with 2.5 μM of the cycloartane. The result is representative of one of three replicates that had essentially similar results.</p

Expression of apoptosis signalling proteins in cycloartane-treated HT-29 cells over various time intervals (6, 12, 18 and 24 hours).

<p>(A) Upregulated proteins detected in human apoptosis antibody array. (B) Fold changes of apoptosis signalling molecules in comparison to control with a cut off limit of 1.5 fold. (C) Western blot analysis of apoptotic signalling proteins in cycloartane treated HT-29 cells and TNF-α-treated as positive control for NFkB translocation over various time intervals (6, 12, 18 and 24 hours).</p

Acridone Alkaloids from <i>Glycosmis chlorosperma</i> as DYRK1A Inhibitors

Two new acridone alkaloids, chlorospermines A and B (<b>1</b> and <b>2</b>), were isolated from the stem bark of <i>Glycosmis chlorosperma</i>, together with the known atalaphyllidine (<b>3</b>) and acrifoline (<b>4</b>), by means of bioguided isolation using an in vitro enzyme assay against DYRK1A. Acrifoline (<b>4</b>) and to a lesser extent chlorospermine B (<b>2</b>) and atalaphyllidine (<b>3</b>) showed significant inhibiting activity on DYRK1A with IC₅₀’s of 0.075, 5.7, and 2.2 μM, respectively. Their selectivity profile was evaluated against a panel of various kinases, and molecular docking calculations provided structural details for the interaction between these compounds and DYRK1A