48 research outputs found
Quantitative <sup>1</sup>H NMR. Development and Potential of an Analytical Method: An Update
Covering the literature from mid-2004 until the end of
2011, this
review continues a previous literature overview on quantitative <sup>1</sup>H NMR (qHNMR) methodology and its applications in the analysis
of natural products. Among the foremost advantages of qHNMR is its
accurate function with external calibration, the lack of any requirement
for identical reference materials, a high precision and accuracy when
properly validated, and an ability to quantitate multiple analytes
simultaneously. As a result of the inclusion of over 170 new references,
this updated review summarizes a wealth of detailed experiential evidence
and newly developed methodology that supports qHNMR as a valuable
and unbiased analytical tool for natural product and other areas of
research
Countercurrent Separation of Natural Products: An Update
This work assesses the current instrumentation,
method development,
and applications in countercurrent chromatography (CCC) and centrifugal
partition chromatography (CPC), collectively referred to as countercurrent
separation (CCS). The article provides a critical review of the CCS
literature from 2007 since our last review (<i>J. Nat. Prod.</i> <b>2008</b>, <i>71</i>, 1489–1508), with
a special emphasis on the applications of CCS in natural products
research. The current state of CCS is reviewed in regard to three
continuing topics (instrumentation, solvent system development, theory)
and three new topics (optimization of parameters, workflow, bioactivity
applications). The goals of this review are to deliver the necessary
background with references for an up-to-date perspective of CCS, to
point out its potential for the natural product scientist, and thereby
to induce new applications in natural product chemistry, metabolome,
and drug discovery research involving organisms from terrestrial and
marine sources
Analysis and Purification of Bioactive Natural Products: The AnaPurNa Study
Based on a meta-analysis of data mined from almost 2000
publications
on bioactive natural products (NPs) from >80 000 pages of
13
different journals published in 1998–1999, 2004–2005,
and 2009–2010, the aim of this systematic review is to provide
both a survey of the status quo and a perspective for analytical methodology
used for isolation and purity assessment of bioactive NPs. The study
provides numerical measures of the common means of sourcing NPs, the
chromatographic methodology employed for NP purification, and the
role of spectroscopy and purity assessment in NP characterization.
A link is proposed between the observed use of various analytical
methodologies, the challenges posed by the complexity of metabolomes,
and the inescapable residual complexity of purified NPs and their
biological assessment. The data provide inspiration for the development
of innovative methods for NP analysis as a means of advancing the
role of naturally occurring compounds as a viable source of biologically
active agents with relevance for human health and global benefit
The Essential Medicinal Chemistry of Curcumin
Curcumin
is a constituent (up to ∼5%) of the traditional
medicine known as turmeric. Interest in the therapeutic use of turmeric
and the relative ease of isolation of curcuminoids has led to their
extensive investigation. Curcumin has recently been classified as
both a PAINS (pan-assay interference compounds) and an IMPS (invalid
metabolic panaceas) candidate. The likely false activity of curcumin
in vitro and in vivo has resulted in >120
clinical trials of curcuminoids against several diseases. No double-blinded,
placebo controlled clinical trial of curcumin has been successful.
This manuscript reviews the essential medicinal chemistry of curcumin
and provides evidence that curcumin is an unstable, reactive, nonbioavailable
compound and, therefore, a highly improbable lead. On the basis of
this in-depth evaluation, potential new directions for research on
curcuminoids are discussed
Natural Deep Eutectic Solvents: Properties, Applications, and Perspectives
As functional liquid media, <u>n</u>atural <u>d</u>eep <u>e</u>utectic <u>s</u>olvent (NADES) species can dissolve
natural or synthetic chemicals
of low water solubility. Moreover, the special properties of NADES,
such as biodegradability and biocompatibility, suggest that they are
alternative candidates for concepts and applications involving some
organic solvents and ionic liquids. Owing to the growing comprehension
of the eutectic mechanisms and the advancing interest in the natural
eutectic phenomenon, many NADES applications have been developed in
the past several years. However, unlike organic solvents, the basic
structural unit of NADES media primarily depends on the intermolecular
interactions among their components. This makes NADES matrices readily
influenced by various factors, such as water content, temperature,
and component ratio and, thus, extends the metabolomic challenge of
natural products (NPs). To enhance the understanding of the importance
of NADES in biological systems, this review focuses on NADES properties
and applications in NP research. The present thorough chronological
and statistical analysis of existing report adds to the recognition
of the distinctiveness of (NA)DES, involves a discussion of NADES-related
observations in NP research, and reportes applications of these eutectic
mixtures. The work identifies potential areas for future studies of
(NA)DES by evaluating relevant applications, including their use as
extraction and chromatographic media as well as their biomedical relevance.
The chemical diversity of natural metabolites that generate or participate
in NADES formation highlights the growing insight that biosynthetically
primordial metabolites (PRIMs) are as essential to the biological
function and bioactivity of unrefined natural products as the biosynthetically
more highly evolutionary metabolites (HEVOs) that can be isolated
from crude mixtures
Digital NMR Profiles as Building Blocks: Assembling <sup>1</sup>H Fingerprints of Steviol Glycosides
This report describes a fragment-based
approach to the examination
of congeneric organic compounds by NMR spectroscopy. The method combines
the classic interpretation of 1D- and 2D-NMR data sets with contemporary
computer-assisted NMR analysis. Characteristic NMR profiles of key
structural motifs were generated by <sup>1</sup>H iterative full spin
analysis and then joined together as building blocks to recreate the <sup>1</sup>H NMR spectra of increasingly complex molecules. To illustrate
the methodology described, a comprehensive analysis of steviol (<b>1</b>), seven steviol glycosides (<b>2</b>–<b>8</b>) and two structurally related isosteviol compounds (<b>9</b>, <b>10</b>) was carried out. The study also assessed
the potential impact of this method on relevant aspects of natural
product research including structural verification, chemical dereplication,
and mixture analysis
Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?
High-throughput biology has contributed
a wealth of data on chemicals,
including natural products (NPs). Recently, attention was drawn to
certain, predominantly synthetic, compounds that are responsible for
disproportionate percentages of hits but are false actives. Spurious
bioassay interference led to their designation as <u>p</u>an-<u>a</u>ssay <u>in</u>terference
compound<u>s</u> (PAINS). NPs lack comparable scrutiny,
which this study aims to rectify. Systematic mining of 80+ years of
the phytochemistry and biology literature, using the NAPRALERT database,
revealed that only 39 compounds represent the NPs most reported by
occurrence, activity, and distinct activity. Over 50% are not explained
by phenomena known for synthetic libraries, and all had manifold ascribed
bioactivities, designating them as <u>i</u>nvalid <u>m</u>etabolic <u>p</u>anaceas (IMPs). Cumulative
distributions of ∼200,000 NPs uncovered that NP research follows
power-law characteristics typical for behavioral phenomena. Projection
into occurrence–bioactivity–effort space produces the
hyperbolic black hole of NPs, where IMPs populate the high-effort
base
Digital NMR Profiles as Building Blocks: Assembling <sup>1</sup>H Fingerprints of Steviol Glycosides
This report describes a fragment-based
approach to the examination
of congeneric organic compounds by NMR spectroscopy. The method combines
the classic interpretation of 1D- and 2D-NMR data sets with contemporary
computer-assisted NMR analysis. Characteristic NMR profiles of key
structural motifs were generated by <sup>1</sup>H iterative full spin
analysis and then joined together as building blocks to recreate the <sup>1</sup>H NMR spectra of increasingly complex molecules. To illustrate
the methodology described, a comprehensive analysis of steviol (<b>1</b>), seven steviol glycosides (<b>2</b>–<b>8</b>) and two structurally related isosteviol compounds (<b>9</b>, <b>10</b>) was carried out. The study also assessed
the potential impact of this method on relevant aspects of natural
product research including structural verification, chemical dereplication,
and mixture analysis
Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?
High-throughput biology has contributed
a wealth of data on chemicals,
including natural products (NPs). Recently, attention was drawn to
certain, predominantly synthetic, compounds that are responsible for
disproportionate percentages of hits but are false actives. Spurious
bioassay interference led to their designation as <u>p</u>an-<u>a</u>ssay <u>in</u>terference
compound<u>s</u> (PAINS). NPs lack comparable scrutiny,
which this study aims to rectify. Systematic mining of 80+ years of
the phytochemistry and biology literature, using the NAPRALERT database,
revealed that only 39 compounds represent the NPs most reported by
occurrence, activity, and distinct activity. Over 50% are not explained
by phenomena known for synthetic libraries, and all had manifold ascribed
bioactivities, designating them as <u>i</u>nvalid <u>m</u>etabolic <u>p</u>anaceas (IMPs). Cumulative
distributions of ∼200,000 NPs uncovered that NP research follows
power-law characteristics typical for behavioral phenomena. Projection
into occurrence–bioactivity–effort space produces the
hyperbolic black hole of NPs, where IMPs populate the high-effort
base
Quantitative Purity–Activity Relationships of Natural Products: The Case of Anti-Tuberculosis Active Triterpenes from <i>Oplopanax horridus</i>
The present study provides an extension of the previously
developed
concept of purity–activity relationships (PARs) and enables
the quantitative evaluation of the effects of multiple minor components
on the bioactivity of residually complex natural products. The anti-tuberculosis
active triterpenes from the Alaskan ethnobotanical <i>Oplopanax
horridus</i> were selected as a case for the development of the
quantitative PAR (QPAR) concept. The residual complexity of the purified
triterpenes was initially evaluated by 1D- and 2D-NMR and identified
as a combination of structurally related and unrelated impurities.
Using a biochemometric approach, the qHNMR purity and anti-TB activity
of successive chromatographic fractions of <i>O. horridus</i> triterpenes were correlated by linear regression analysis to generate
a mathematical QPAR model. The results demonstrate that impurities,
such as widely occurring monoglycerides, can have a profound impact
on the observed antimycobacterial activity of triterpene-enriched
fractions. The QPAR concept is shown to be capable of providing a
quantitative assessment in situations where residually complex constitution
contributes toward the biological activity of natural products