10 research outputs found
Hemopressin-Based pH-Sensitive Hydrogel: A Potential Bioactive Platform for Drug Delivery
Peptides
with proper sequences are capable of self-assembling into
well-defined nanostructures, which can subsequently grow and entangle
into three-dimensional nanomatrices. In this study, hemopressin, a
cannabinoid receptor-modulating peptide derived from the α-chain
of hemoglobin known to self-assemble into nanofibrils, was examined
for its potential applicability as a gelator. The results indicated
that hemopressin’s gel formation was dependent on pH and salt
concentration. Although hemopressin’s macroscopic states showed
differences, its microscopic structure remained largely unchanged
in which it consisted mainly of the antiparallel β-sheet conformation
as confirmed by FTIR (C=O stretch peaks at 1630 and 1695 cm<sup>–1</sup>) and CD (β-sheet peak at 195 nm). The major difference between
the gel and sol states was displayed in the fibril length in which
the gelation at pH 7.4 resulted in 4 μm fibrils, whereas the
solution at pH 5.0 showed 800 nm fibrils. The pH-dependent sol–gel
phase transition property was then utilized for the investigation
of the pH-responsive release of FITC-dextran (4–40 kDa) from
hemopressin fibrillary gel. Finally, the biocompatibility of the peptide
was demonstrated by proliferation assay of cultured bone marrow mesenchymal
stem cells. Altogether, the results suggested that hemopressin is
a potentially promising candidate as a therapeutically active platform
for drug delivery
Synthesis of Natural Acylphloroglucinol-Based Antifungal Compounds against <i>Cryptococcus</i> Species
Thirty-three natural-product-based
acylphloroglucinol derivatives
were synthesized to identify antifungal compounds against <i>Cryptococcus</i> spp. that cause the life-threatening disseminated
cryptococcosis. In vitro antifungal testing showed that 17 compounds
were active against <i>C. neoformans</i> ATCC 90113, <i>C. neoformans</i> H99, and <i>C. gattii</i> ATCC 32609,
with minimum inhibitory concentrations (MICs) in the range 1.0–16.7
μg/mL. Analysis of the structure and antifungal activity of
these compounds indicated that the 2,4-diacyl- and 2-acyl-4-alkylphloroglucinols
were more active than <i>O</i>-alkyl-acylphloroglucinols.
The most promising compound found was 2-methyl-1-(2,4,6-trihydroxy-3-(4-isopropylbenzyl)Âphenyl)Âpropan-1-one
(<b>11j</b>), which exhibited potent antifungal activity (MICs,
1.5–2.1 μg/mL) and low cytotoxicity against the mammalian
Vero and LLC-PK1 cell lines (IC<sub>50</sub> values >50 μg/mL).
This compound may serve as a template for further synthesis of new
analogues with improved antifungal activity. The findings of the present
work may contribute to future antifungal discovery toward pharmaceutical
development of new treatments for cryptococcosis
Synthesis and Antimicrobial Evaluation of Fire Ant Venom Alkaloid Based 2‑Methyl-6-alkyl‑Δ<sup>1,6</sup>-piperideines
The first synthesis of 2-methyl-6-pentadecyl-Δ<sup>1,6</sup>-piperideine (<b>1</b>), a major alkaloid of the piperideine
chemotype in fire ant venoms, and its analogues, 2-methyl-6-tetradecyl-Δ<sup>1,6</sup>-piperideine (<b>2</b>) and 2-methyl-6-hexadecyl-Δ<sup>1,6</sup>-piperideine (<b>3</b>), was achieved by a facile
synthetic method starting with glutaric acid (<b>4</b>) and
urea (<b>5</b>). Compound <b>1</b> showed in vitro antifungal
activity against <i>Cryptococcus neoformans</i> and <i>Candida albicans</i> with IC<sub>50</sub> values of 6.6 and
12.4 μg/mL, respectively, and antibacterial activity against
vancomycin-resistant <i>Enterococcus faecium</i> with an
IC<sub>50</sub> value of 19.4 μg/mL, while compounds <b>2</b> and <b>3</b> were less active against these pathogens. All
three compounds strongly inhibited the parasites <i>Leishmania
donovani</i> promastigotes and <i>Trypanosoma brucei</i> with IC<sub>50</sub> values in the range of 5.0–6.7 and 2.7–4.0
μg/mL, respectively
Antibacterial Prenylated Acylphloroglucinols from <i>Psorothamnus fremontii</i>
Psorothatins A–C (<b>1</b>–<b>3</b>),
three antibacterial prenylated acylphloroglucinol derivatives, were
isolated from the native American plant <i>Psorothamnus fremontii</i>. They feature an unusual α,β-epoxyketone functionality
and a β-hydroxy-α,β-unsaturated ketone structural
moiety. The latter forms a pseudo-six-membered heterocyclic ring due
to strong intramolecular hydrogen bonding, as indicated by the long-range
proton–carbon correlations in the NMR experiments. Psorothatin
C (<b>3</b>) was the most active compound against methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin-resistant <i>Enterococcus
faecium</i>, with IC<sub>50</sub> values in the range 1.4–8.8
μg/mL. The first total synthesis of <b>3</b> described
herein permits future access to structural analogues with potentially
improved antibacterial activities
Chemical Composition and Acetylcholinesterase Inhibitory Activity of Essential Oils from <i>Piper</i> Species
The
essential oils (EOs) derived from aromatic plants such as <i>Piper</i> species are considered to play a role in alleviating
neuronal ailments that are associated with inhibition of acetylcholinesterase
(AChE). The chemical compositions of 23 EOs prepared from 16 <i>Piper</i> spp. were analyzed by both gas chromatography with
a flame ionization detector (GC-FID) and gas chromatography–mass
spectrometry (GC-MS). A total of 76 compounds were identified in the
EOs from the leaves and stems of 19 samples, while 30 compounds were
detected in the EOs from the fruits of four samples. Sesquiterpenes
and phenylpropanoids were found to be rich in these EOs, of which
asaricin, caryophyllene, caryophyllene oxide, isospathulenol, (+)-spathulenol,
and β-bisabolene are the major constituents. The EOs from the
leaves and stems of <i>Piper austrosinense</i>, <i>P. puberulum</i>, <i>P. flaviflorum</i>, <i>P. betle</i>, and <i>P. hispidimervium</i> showed
strong AChE inhibitory activity with IC<sub>50</sub> values in the
range of 1.51 to 13.9 mg/mL. A thin-layer chromatography (TLC) bioautography
assay was employed to identify active compound(s) in the most active
EO from <i>P. hispidimervium</i>. The active compound was
isolated and identified as asaricin, which gave an IC<sub>50</sub> value of 0.44 ± 0.02 mg/mL against AChE, comparable to galantamine
with an IC<sub>50</sub> 0.15 ± 0.01 mg/mL
Bacillusin A, an Antibacterial Macrodiolide from <i>Bacillus amyloliquefaciens</i> AP183
Bioassay-guided fractionation of
the organic extracts of a <i>Bacillus amyloliquefaciens</i> strain (AP183) led to the discovery
of a new macrocyclic polyene antibiotic, bacillusin A (<b>1</b>). Its structure was assigned by interpretation of NMR and MS spectroscopic
data as a novel macrodiolide composed of dimeric 4-hydroxy-2-methoxy-6-alkenylbenzoic
acid lactones with conjugated pentaene-hexahydroxy polyketide chains.
Compound <b>1</b> showed potent antibacterial activities against
methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin-resistant <i>Enterococcus faecium</i> with minimum inhibitory concentrations
in a range of 0.6 to 1.2 μg/mL. The biosynthetic significance
of this unique class of antibiotic compounds is briefly discussed
LC-MS- and <sup>1</sup>H NMR Spectroscopy-Guided Identification of Antifungal Diterpenoids from <i>Sagittaria latifolia</i>
Antifungal screening of small-molecule
natural product libraries
showed that a column fraction (CF) derived from the plant extract
of <i>Sagittaria latifolia</i> was active against the fungal
pathogen <i>Cryptococcus neoformans</i>. Dereplication analysis
by liquid chromatography–mass spectrometry (LC-MS) and proton
nuclear magnetic resonance spectroscopy (<sup>1</sup>H NMR) indicated
the presence of new compounds in this CF. Subsequent fractionation
of the plant extract resulted in the identification of two new isopimaradiene-type
diterpenoids, <b>1</b> and <b>2</b>. The structures of <b>1</b> and <b>2</b> were determined by chemical methods and
spectroscopic analysis as isopimara-7,15-dien-19-ol 19-<i>O</i>-α-l-arabinofuranoside and isopimara-7,15-dien-19-ol
19-<i>O</i>-α-l-(5′-acetoxy)Âarabinofuranoside,
respectively. Compound <b>1</b> exhibited IC<sub>50</sub> values
of 3.7 and 1.8 μg/mL, respectively, against <i>C. neoformans
and C. gattii</i>. Its aglycone, isopimara-7,15-dien-19-ol (<b>3</b>), resulting from acid hydrolysis of <b>1</b>, was
also active against the two fungal pathogens, with IC<sub>50</sub> values of 9.2 and 6.8 μg/mL, respectively. This study demonstrates
that utilization of the combined LC-MS and <sup>1</sup>H NMR analytical
tools is an improved chemical screening approach for hit prioritization
in natural product drug discovery
Chemical constituents from <i>Piper wallichii</i>
<div><p>Fifteen known compounds including four triterpenoids (<b>1</b>–<b>4</b>), one sterol (<b>5</b>), one diketopiperazine alkaloid (<b>6</b>) and nine phenolics (<b>7</b>–<b>15</b>) were isolated from the stems of <i>Piper wallichii</i>. Their structures were elucidated by means of spectroscopic analysis, and acidic hydrolysis in case of the 2-oxo-3β,19α,23-trihydroxyurs-12-en-28-oic acid β-D-glucopyranosyl ester (<b>1</b>). The structure of compound <b>1</b> was fully assigned by 1D and 2D NMR experiments for the first time. All isolates were tested for their antibacterial, antifungal, anti-inflammatory and antiplatelet aggregation bioactivities.</p></div
Biological evaluation of phytoconstituents from <i>Polygonum hydropiper</i>
<p>Fourteen compounds including vanicoside B (<b>1</b>), vanicoside F (<b>2</b>), vanicoside E (<b>3</b>) and 5,6-dehydrokawain (<b>4</b>), aniba-dimer-A (<b>5</b>), 6,6′-((1<i>α</i>,2<i>α</i>,3<i>β</i>,4<i>β</i>)-2,4-diphenylcyclobutane-1,3-diyl)bis(4-methoxy-2<i>H</i>-pyran-2-one) (<b>6</b>), (+)-ketopinoresinol (<b>7</b>), isorhamnetin (<b>8</b>), 3,7-dihydroxy-5,6-dimethoxy-flavone (<b>9</b>), isalpinin (<b>10</b>), cardamomin (<b>11</b>), pinosylvin (<b>12</b>), 2-desoxy-4-<i>epi</i>-pulchellin (<b>13</b>) and <i>β</i>-sitosterol (<b>14</b>) were isolated from dichloromethane-soluble portion of <i>Polygonum hydropiper</i>. By using Alamar blue assay, compounds <b>2</b>, <b>7</b>, <b>8</b>, <b>11</b> and <b>12</b> were found to be active against <i>Trypanosoma brucei</i> with IC<sub>50</sub> values in the range of 0.49–7.77 μg/mL. Cardamomin (<b>11</b>) had most significant activity against <i>T. brucei</i> with IC<sub>50</sub>/IC<sub>90</sub> values of 0.49/0.81 μg/mL compared to the positive control DFMO (IC<sub>50</sub>/IC<sub>90</sub>: 3.02/8.05 μg/mL). Furthermore, in antimalarial, antimicrobial, anti-inflammatory, PPAR and cytotoxic assays, some compounds have demonstrated moderate inhibitory potentials.</p
UPLC-MS-ELSD-PDA as a Powerful Dereplication Tool to Facilitate Compound Identification from Small-Molecule Natural Product Libraries
The generation of natural product
libraries containing column fractions,
each with only a few small molecules, using a high-throughput, automated
fractionation system, has made it possible to implement an improved
dereplication strategy for selection and prioritization of leads in
a natural product discovery program. Analysis of databased UPLC-MS-ELSD-PDA
information of three leads from a biological screen employing the
ependymoma cell line EphB2-EPD generated details on the possible structures
of active compounds present. The procedure allows the rapid identification
of known compounds and guides the isolation of unknown compounds of
interest. Three previously known flavanone-type compounds, homoeriodictyol
(<b>1</b>), hesperetin (<b>2</b>), and sterubin (<b>3</b>), were identified in a selected fraction derived from the
leaves of <i>Eriodictyon angustifolium</i>. The lignan compound
deoxypodophyllotoxin (<b>8</b>) was confirmed to be an active
constituent in two lead fractions derived from the bark and leaves
of <i>Thuja occidentalis</i>. In addition, two new but inactive
labdane-type diterpenoids with an uncommon triol side chain were also
identified as coexisting with deoxypodophyllotoxin in a lead fraction
from the bark of <i>T. occidentalis.</i> Both diterpenoids
were isolated in acetylated form, and their structures were determined
as 14<i>S</i>,15-diacetoxy-13<i>R</i>-hydroxylabd-8Â(17)-en-19-oic
acid (<b>9</b>) and 14<i>R</i>,15-diacetoxy-13<i>S</i>-hydroxylabd-8Â(17)-en-19-oic acid (<b>10</b>), respectively,
by spectroscopic data interpretation and X-ray crystallography. This
work demonstrates that a UPLC-MS-ELSD-PDA database produced during
fractionation may be used as a powerful dereplication tool to facilitate
compound identification from chromatographically tractable small-molecule
natural product libraries