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

---

Discovery and resupply of pharmacologically active plant-derived natural products: A review

Biotechnology Advances, Journal Year: 2015, Volume and Issue: 33(8), P. 1582 - 1614

Published: Aug. 15, 2015

Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification novel drug leads. In past decades, pharmaceutical industry focused mainly on libraries synthetic compounds discovery source. They are comparably easy to produce resupply, demonstrate good compatibility established high throughput screening (HTS) platforms. However, at same time there has been declining trend in number new drugs reaching market, raising renewed scientific interest from natural sources, despite its known challenges. this survey, brief outline historical development is provided together comprehensive overview used approaches recent developments relevant plant-derived product discovery. Associated challenges major strengths product-based critically discussed. A snapshot advanced products that currently actively recruiting clinical trials also presented. Importantly, transition compound “screening hit” through “drug lead” “marketed drug” associated increasingly challenging demands amount, which often cannot be met by re-isolation respective plant sources. regard, existing alternatives resupply discussed, including different biotechnology total organic synthesis. While intrinsic complexity necessitates highly integrated interdisciplinary approaches, reviewed developments, technological advances, research trends clearly indicate will among most sources future.

Language: Английский

---

Proteomics: Technologies and Their Applications

Journal of Chromatographic Science, Journal Year: 2016, Volume and Issue: 55(2), P. 182 - 196

Published: Oct. 18, 2016

Proteomics involves the applications of technologies for identification and quantification overall proteins present content a cell, tissue or an organism. It supplements other "omics" such as genomic transcriptomics to expound identity organism, cognize structure functions particular protein. Proteomics-based are utilized in various capacities different research settings detection diagnostic markers, candidates vaccine production, understanding pathogenicity mechanisms, alteration expression patterns response signals interpretation functional protein pathways diseases. is practically intricate because it includes analysis categorization signatures genome. Mass spectrometry with LC-MS-MS MALDI-TOF/TOF being widely used equipment central among current proteomics. However, utilization proteomics facilities including software equipment, databases requirement skilled personnel substantially increase costs, therefore limit their wider use especially developing world. Furthermore, proteome highly dynamic complex regulatory systems that control levels proteins. This review efforts describe approaches, recent developments application analysis.

Language: Английский

---

Toward Merging Untargeted and Targeted Methods in Mass Spectrometry-Based Metabolomics and Lipidomics

Analytical Chemistry, Journal Year: 2015, Volume and Issue: 88(1), P. 524 - 545

Published: Dec. 4, 2015

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTToward Merging Untargeted and Targeted Methods in Mass Spectrometry-Based Metabolomics LipidomicsTomas Cajka† Oliver Fiehn*†‡View Author Information† UC Davis Genome Center−Metabolomics, University of California Davis, 451 Health Sciences Drive, 95616, United States‡ King Abdulaziz University, Faculty Science, Biochemistry Department, P.O. Box 80203, Jeddah 21589, Saudi Arabia*Phone: +1-530-754-8258. Fax: +1-530-754-9658. E-mail: [email protected]Cite this: Anal. Chem. 2016, 88, 1, 524–545Publication Date (Web):December 4, 2015Publication History Published online16 December 2015Published inissue 5 January 2016https://pubs.acs.org/doi/10.1021/acs.analchem.5b04491https://doi.org/10.1021/acs.analchem.5b04491review-articleACS PublicationsCopyright © 2015 American Chemical SocietyRequest reuse permissionsArticle Views20448Altmetric-Citations571LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated to reflect usage leading up last few days.Citations number other articles citing this article, calculated by Crossref daily. Find more information about citation counts.The Altmetric Attention Score is a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence for given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Ions,Lipidomics,Lipids,Metabolism,Metabolomics Get e-Alerts

Language: Английский

---

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

---

Integration of Molecular Networking and In-Silico MS/MS Fragmentation for Natural Products Dereplication

Analytical Chemistry, Journal Year: 2016, Volume and Issue: 88(6), P. 3317 - 3323

Published: Feb. 16, 2016

Dereplication represents a key step for rapidly identifying known secondary metabolites in complex biological matrices. In this context, liquid-chromatography coupled to high resolution mass spectrometry (LC-HRMS) is increasingly used and, via untargeted data-dependent MS/MS experiments, massive amounts of detailed information on the chemical composition crude extracts can be generated. An efficient exploitation such data sets requires automated treatment and access dedicated fragmentation databases. Various novel bioinformatics approaches as molecular networking (MN) in-silico tools have emerged recently provide new perspective early metabolite identification natural products (NPs) research. Here we propose an innovative dereplication strategy based combination MN with extensive database NPs. Using two case studies, demonstrate that combined approach offers powerful tool navigate through chemistry NPs extracts, dereplicate metabolites, annotate analogues entries.

Language: Английский

---

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

---

Functional metabolomics: from biomarker discovery to metabolome reprogramming

Protein & Cell, Journal Year: 2015, Volume and Issue: 6(9), P. 628 - 637

Published: July 1, 2015

Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible characteristics and revealing mechanisms, which construct the content of discovery metabolomics. The can be used to reprogram metabolome, leading an aimed strategy cope with alteration internal external environments, naming reprogramming metabolomics here. striking feature on similarity basic pathways components among vastly different species makes possible when engineered metabolites play biological roles in cellular activity substrate enzymes regulator other molecules including proteins. approach clarify mechanisms responding changed environmental factors establish framework develop targeted tools dealing changes such controlling and/or preventing infection pathogens enhancing host immunity against pathogens. This review introduces current state trends highlights importance

Language: Английский

---

Advances in mass spectrometry-based metabolomics for investigation of metabolites

RSC Advances, Journal Year: 2018, Volume and Issue: 8(40), P. 22335 - 22350

Published: Jan. 1, 2018

Metabolomics is the systematic study of all metabolites present within a biological system, which consists mass molecules, having variety physical and chemical properties existing over an extensive dynamic range in samples. Diverse analytical techniques are needed to achieve higher coverage metabolites. The application spectrometry (MS) metabolomics has increased exponentially since discovery development electrospray ionization matrix-assisted laser desorption techniques. Significant advances have also occurred separation-based MS (gas chromatography-mass spectrometry, liquid capillary electrophoresis-mass ion mobility-mass spectrometry), as well separation-free (direct infusion-mass ionization-mass imaging, direct analysis real time spectrometry) past decades. This review presents brief overview recent advanced their latest applications metabolomics. software/websites for result analyses reviewed.

Language: Английский

---

Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?

Journal of Medicinal Chemistry, Journal Year: 2015, Volume and Issue: 59(5), P. 1671 - 1690

Published: Oct. 27, 2015

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 hits but false actives. Spurious bioassay interference led their designation as pan-assay (PAINS). NPs lack comparable scrutiny, which this study aims rectify. Systematic mining 80+ years the phytochemistry and literature, using NAPRALERT database, revealed only 39 represent most reported by occurrence, activity, distinct activity. Over 50% not explained phenomena known synthetic libraries, all had manifold ascribed bioactivities, designating them invalid metabolic panaceas (IMPs). Cumulative distributions ∼200,000 uncovered NP research follows power-law characteristics typical behavioral phenomena. Projection into occurrence–bioactivity–effort space produces hyperbolic black hole NPs, where IMPs populate high-effort base.

Language: Английский

---