Natural products in drug discovery: advances and opportunities

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(3), P. 200 - 216

Published: Jan. 28, 2021

Language: Английский

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Metabolomics for Investigating Physiological and Pathophysiological Processes

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(4), P. 1819 - 1875

Published: Aug. 22, 2019

Metabolomics uses advanced analytical chemistry techniques to enable the high-throughput characterization of metabolites from cells, organs, tissues, or biofluids. The rapid growth in metabolomics is leading a renewed interest metabolism and role that small molecule play many biological processes. As result, traditional views as being simply “bricks mortar” cells just fuel for cellular energetics are upended. Indeed, appear have much more varied far important roles signaling molecules, immune modulators, endogenous toxins, environmental sensors. This review explores how yielding new insights into number physiological In particular, major focus on illustrating discoveries made through improving our understanding both normal physiology pathophysiology diseases. These influence organ function, nutrient sensing, gut physiology. Collectively, this work unified system-wide perspective biology wherein metabolites, proteins, genes understood interact synergistically modify actions functions organelles, organisms.

Language: Английский

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Software Tools and Approaches for Compound Identification of LC-MS/MS Data in Metabolomics

Metabolites, Journal Year: 2018, Volume and Issue: 8(2), P. 31 - 31

Published: May 10, 2018

The annotation of small molecules remains a major challenge in untargeted mass spectrometry-based metabolomics. We here critically discuss structured elucidation approaches and software that are designed to help during the unknown compounds. Only by elucidating metabolites first is it possible biologically interpret complex systems, map compounds pathways create reliable predictive metabolic models for translational clinical research. These strategies include construction quality tandem spectral databases such as coalition MassBank repositories investigations MS/MS matching confidence. present silico fragmentation tools MS-FINDER, CFM-ID, MetFrag, ChemDistiller CSI:FingerID can annotate from existing structure have been used CASMI (critical assessment molecule identification) contests. Furthermore, use retention time liquid chromatography utility collision cross-section modelling ion mobility experiments covered. Workflows published examples successfully annotated included.

Language: Английский

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Systematic classification of unknown metabolites using high-resolution fragmentation mass spectra

Nature Biotechnology, Journal Year: 2020, Volume and Issue: 39(4), P. 462 - 471

Published: Nov. 23, 2020

Language: Английский

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Identification of small molecules using accurate mass MS/MS search

Mass Spectrometry Reviews, Journal Year: 2017, Volume and Issue: 37(4), P. 513 - 532

Published: April 24, 2017

Tandem mass spectral library search (MS/MS) is the fastest way to correctly annotate MS/MS spectra from screening small molecules in fields such as environmental analysis, drug screening, lipid and metabolomics. The confidence MS/MS‐based annotation of chemical structures impacted by instrumental settings requirements, data acquisition modes including data‐dependent data‐independent methods, scoring algorithms, well post‐curation steps. We critically discuss parameters that influence results, accuracy, precursor ion isolation width, intensity thresholds, centroiding speed. A range publicly commercially available databases NIST, MassBank, MoNA, LipidBlast, Wiley MSforID, METLIN are surveyed. In addition, software tools NIST MS Search, MS‐DIAL, Mass Frontier, SmileMS, Mass++, XCMS 2 perform fast discussed. algorithms challenges during compound reviewed. Advanced methods silico generation tandem using quantum chemistry machine learning covered. Community efforts for curation sharing will allow faster distribution scientific discoveries

Language: Английский

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Bioactivity-Based Molecular Networking for the Discovery of Drug Leads in Natural Product Bioassay-Guided Fractionation

Journal of Natural Products, Journal Year: 2018, Volume and Issue: 81(4), P. 758 - 767

Published: March 2, 2018

It is a common problem in natural product therapeutic lead discovery programs that despite good bioassay results the initial extract, active compound(s) may not be isolated during subsequent bioassay-guided purification. Herein, we present concept of bioactive molecular networking to find candidate molecules directly from fractionated extracts. By employing tandem mass spectrometry, it possible accelerate dereplication using prior isolation compounds, and also expose potentially bioactivity score prediction. Indeed, prediction can calculated with relative abundance molecule fractions level each fraction. For reason, have developed bioinformatic workflow able map networks applied for antiviral compounds previously investigated extract Euphorbia dendroides where were discovered following classical fractionation procedure. expected this approach will implemented as systematic strategy, only current future collections but reinvestigation untapped reservoir analogues previous efforts.

Language: Английский

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Propagating annotations of molecular networks using in silico fragmentation

PLoS Computational Biology, Journal Year: 2018, Volume and Issue: 14(4), P. e1006089 - e1006089

Published: April 18, 2018

The annotation of small molecules is one the most challenging and important steps in untargeted mass spectrometry analysis, as our biological interpretations rely on structural annotations. Molecular networking has emerged a structured way to organize mine data from tandem (MS/MS) experiments been widely applied propagate However, propagation done through manual inspection MS/MS spectra connected spectral networks only possible when reference library spectrum available. One alternative approaches used annotate an unknown fragmentation use silico predictions. challenges uncertainty around correct structure among predicted candidate lists. Here we show how molecular can be improve accuracy predictions annotations, even there no match libraries. This accomplished creating network consensus re-ranked candidates using topology similarity Network Annotation Propagation (NAP) tool accessible GNPS web-platform https://gnps.ucsd.edu/ProteoSAFe/static/gnps-theoretical.jsp.

Language: Английский

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Molecular Networking As a Drug Discovery, Drug Metabolism, and Precision Medicine Strategy

Trends in Pharmacological Sciences, Journal Year: 2016, Volume and Issue: 38(2), P. 143 - 154

Published: Nov. 11, 2016

Language: Английский

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Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery

Chemical Reviews, Journal Year: 2020, Volume and Issue: 121(6), P. 3495 - 3560

Published: Nov. 9, 2020

The crisis of antibiotic resistance necessitates creative and innovative approaches, from chemical identification analysis to the assessment bioactivity. Plant natural products (NPs) represent a promising source antibacterial lead compounds that could help fill drug discovery pipeline in response growing crisis. major strength plant NPs lies their rich unique chemodiversity, worldwide distribution ease access, various modes action, proven clinical effectiveness extracts which they are isolated. While many studies have tried summarize with activities, comprehensive review rigorous selection criteria has never been performed. In this work, literature 2012 2019 was systematically reviewed highlight plant-derived activity by focusing on growth inhibitory activity. A total 459 included Review, 50.8% phenolic derivatives, 26.6% terpenoids, 5.7% alkaloids, 17% classified as other metabolites. 183 is further discussed regarding activity, biosynthesis, structure-activity relationship, mechanism potential antibiotics. Emerging trends field plants also discussed. This Review brings forefront key findings for consideration future development efforts.

Language: Английский

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CFM-ID 3.0: Significantly Improved ESI-MS/MS Prediction and Compound Identification

Metabolites, Journal Year: 2019, Volume and Issue: 9(4), P. 72 - 72

Published: April 13, 2019

Metabolite identification for untargeted metabolomics is often hampered by the lack of experimentally collected reference spectra from tandem mass spectrometry (MS/MS). To circumvent this problem, Competitive Fragmentation Modeling-ID (CFM-ID) was developed to accurately predict electrospray ionization-MS/MS (ESI-MS/MS) chemical structures and aid in compound via MS/MS spectral matching. While earlier versions CFM-ID performed very well, CFM-ID’s performance predicting certain classes compounds, including many lipids, quite poor. Furthermore, capabilities were limited because it did not use available nor exploit metadata its matching algorithm. Here, we describe significant improvements speed. These include (1) implementation a rule-based fragmentation approach lipid prediction, which greatly improves speed accuracy CFM-ID; (2) inclusion experimental other enhance abilities; (3) development new scoring functions that 21.1%; (4) classification algorithm correctly classifies unknown chemicals (based on their spectra) >80% cases. This improved version called 3.0 freely as web server. Its source code also accessible online.

Language: Английский

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