New furocarbazole alkaloids from <i>Lonicera quinquelocularis</i>

<div><p>Two new furocarbazole alkaloids, 3-formyl-6,7-dimethoxy-furo[1,2]carbazole (<b>1</b>) and methyl-6,7-dimethoxy-furo[1,2]carbazole-3-carboxylate (<b>2</b>), along with two known carbazole alkaloids, 3-formyl-2-hydroxy-7-methoxycarbazole (<b>3</b>) and methyl 2,7-dimethoxycarbazole-3-carboxylate (<b>4</b>) were isolated from the ethyl acetate soluble fraction of <i>Lonicera quinquelocularis</i>. Their structures were established on the basis of spectroscopic analysis.</p></div

New Cholinesterase Inhibitory Constituents from <i>Lonicera quinquelocularis</i>

<div><p>A phytochemical investigation on the ethyl acetate soluble fraction of <i>Lonicera quinquelocularis</i> (whole plant) led to the first time isolation of one new phthalate; <i>bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate</i> (<b>3</b>) and two new benzoates; <i>neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate</i> (<b>4</b>) <i>and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate</i> (<b>5</b>) along with two known compounds <i>bis (2-ethylhexyl phthalate</i> (<b>1</b>) and <i>dioctyl phthalate</i> (<b>2</b>). Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (<b>1–5</b>) were tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in dose dependent manner. The IC₅₀ (50% inhibitory effect) values of compounds <b>3</b> and <b>5</b> against AChE were 1.65 and 3.43 µM while the values obtained against BChE were 5.98 and 9.84 µM respectively. Compounds <b>2</b> and <b>4</b> showed weak inhibition profile.</p></div

¹H and ¹³C NMR data (CDCl₃) and ¹H/¹³C correlations of compounds <b>4</b> and <b>5</b> (δ in ppm, <i>J</i> in Hz).

<p>¹H and ¹³C NMR data (CDCl₃) and ¹H/¹³C correlations of compounds <b>4</b> and <b>5</b> (δ in ppm, <i>J</i> in Hz).</p

Structures of compounds 1–5 from <i>L. quinquelocularis</i>.

<p>Structures of compounds 1–5 from <i>L. quinquelocularis</i>.</p

HMBC (H–C) correlations in compound 3.

<p>HMBC (H–C) correlations in compound 3.</p

Important HMBC correlations in 4 (H→C).

<p>Important HMBC correlations in 4 (H→C).</p

AChE and BChE inhibitory activities of compound <b>1</b>–<b>5</b> from <i>L. quinquelocularis</i> (IC₅₀, µM).

a<p>Standard error of mean of five assays.</p>b<p>Positive control used in the assays.</p><p>Note: Data shown are values from triplicate experiments.</p

¹H and ¹³C NMR data and important HMBC correlations of compound <b>3</b> (CDCl₃, δ in ppm, <i>J</i> in Hz).

<p>¹H and ¹³C NMR data and important HMBC correlations of compound <b>3</b> (CDCl₃, δ in ppm, <i>J</i> in Hz).</p

Macrocyclic β-Sheet Peptides That Inhibit the Aggregation of a Tau-Protein-Derived Hexapeptide

This paper describes studies of a series of macrocyclic β-sheet peptides <b>1</b> that inhibit the aggregation of a tau-protein-derived peptide. The macrocyclic β-sheet peptides comprise a pentapeptide “upper” strand, two δ-linked ornithine turn units, and a “lower” strand comprising two additional residues and the β-sheet peptidomimetic template “Hao”. The tau-derived peptide Ac-VQIVYK-NH₂ (AcPHF6) aggregates in solution through β-sheet interactions to form straight and twisted filaments similar to those formed by tau protein in Alzheimer’s neurofibrillary tangles. Macrocycles <b>1</b> containing the pentapeptide VQIVY in the “upper” strand delay and suppress the onset of aggregation of the AcPHF6 peptide. Inhibition is particularly pronounced in macrocycles <b>1a</b>, <b>1d</b>, and <b>1f</b>, in which the two residues in the “lower” strand provide a pattern of hydrophobicity and hydrophilicity that matches that of the pentapeptide “upper” strand. Inhibition varies strongly with the concentration of these macrocycles, suggesting that it is cooperative. Macrocycle <b>1b</b> containing the pentapeptide QIVYK shows little inhibition, suggesting the possibility of a preferred direction of growth of AcPHF6 β-sheets. On the basis of these studies, a model is proposed in which the AcPHF6 amyloid grows as a layered pair of β-sheets and in which growth is blocked by a pair of macrocycles that cap the growing paired hydrogen-bonding edges. This model provides a provocative and appealing target for future inhibitor design