Frontiers in Natural Products最新文献

{"title":"Absolute configuration assignment of marine natural products in Brazil","authors":"A. Batista, Fernando M. dos Santos, A. Valverde","doi":"10.3389/fntpr.2023.1224564","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1224564","url":null,"abstract":"Brazil is one of the most biodiverse countries in the world, with a coastline that stretches over 7,000 km including various marine ecosystems, such as coral reefs, mangroves, and seagrass beds, among other habitats. These diverse environments provide a rich source of compounds, derived from primary or secondary metabolism, which may have countless biological activities. Research on marine natural products (MNP) in Brazil has been ongoing for several decades and led to the discovery of numerous bioactive compounds with potential applications in medicine, agriculture, and cosmetics. These MNP are structurally complex, both from an architectural and stereochemical point of view. However, even with all the well-established techniques for the absolute configuration (AC) assignment, this stage of structural characterization of natural products is still under-explored and remains a challenge. This review presents an overview of natural product chemistry in Brazil, focusing on the stereochemical assignment of marine chiral compounds. The main goals are to describe the techniques employed in the assignments as well as to highlight the importance of choosing the appropriate methods for chiral natural products AC determinations.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"279 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127104545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in the development of CB1R selective probes","authors":"Arianna Amenta, Diego Caprioglio, Alberto Minassi, L. Panza, D. Passarella, V. Fasano, D. Imperio","doi":"10.3389/fntpr.2023.1196321","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1196321","url":null,"abstract":"Cannabinoid subtype 1 receptors (CB1Rs) are an important class of G protein-coupled receptors (GPCRs) belonging to the endocannabinoid system. CB1Rs play a crucial modulatory role in the functioning of other neurotransmitter systems and are involved in a wide range of physiological functions and dysfunctions; thus, they are considered one of the most important targets for drug development, as well as diagnostic purposes. Despite this, only a few molecules targeting this receptor are available on the pharmaceutical market, thus emphasizing the need to gain a deeper understanding of the complex activation pathways of CB1Rs and how they regulate diseases. As part of this review, we provide an overview of pharmacological and imaging tools useful for detecting CB1Rs. Herein, we summarize the derivations of cannabinoids and terpenoids with fluorescent compounds, radiotracers, or photochromic motifs. CB1Rs’ molecular probes may be used in vitro and, in some cases, in vivo for investigating and exploring the roles of CB1Rs together with the starting point for the development of CB1R-targeted drugs.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125220281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and biological evaluation of hydroxamate isosteres of acidic cannabinoids","authors":"H. I. M. Amin, F. Ruíz-Pino, J. Collado, G. Appendino, M. Tena-Sempere, E. Muñoz, Diego Caprioglio","doi":"10.3389/fntpr.2023.1190053","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1190053","url":null,"abstract":"Despite their early discovery, the bioactivity of acidic cannabinoids was long overlooked. Issues of stability and a pharmacological focus on Δ9-THC and its biological profile combined to relegate the non-narcotic native form of phytocannabinoids to a sort of investigational limbo. Recent studies have disclosed an attractive bioactivity profile for specific acidic phytocannabinoids but concerns about their limited stability have remained substantially unaddressed. To solve this issue, we have developed the hydroxamate derivatives of Δ8-tetrahydrocannabinolic acid-A (Δ8-THCA-AH, 6) and cannabidiolic acid (CBDAH, 5) as novel acidic cannabinoid bioisosteres, and we report here their synthesis and bioactivity profile against specific cannabinoid targets, as well as promising in vivo activity in a murine model of polycystic ovary syndrome (PCOS) associated with obesity.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"81 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133832893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Insights in structural and stereochemical analysis: 2022","authors":"J. Batista, Q. Cass","doi":"10.3389/fntpr.2023.1224424","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1224424","url":null,"abstract":"With four articles, including one perspective, two reviews, and one original research article, the Research Topic Insights in Structural and Stereochemical Analysis: 2022 covers the state-of-the-art research being conducted in the analysis of the structure and 3D arrangements of natural product (NP) molecules. In the perspective article by Lopes and da Silva, mass spectrometry and some advanced landmarks are highlighted in respect to the main challenges and impacts of the chemical characterization of complex molecular structures. In this respect, the complexity of data analysis is discussed as one of the main limitations for time-limited tasks. Moreover, the observed expansion in the mass spectral database is not sufficient for the necessary data interpretation. As emphasized by the authors, the estimated number of spectra for ESI-MS/ MS in the public domain is in the order of 60,000 molecules, which is far below the chemical space, and “traditionally, most spectrometry techniques rely on database matching of previously characterized signals.” Meanwhile, the importance of the recently created large public databases is acknowledged as a means of characterizing large datasets acquired in complex samples such as NP extracts. Machine learning (ML)-based methods are also examined regarding their contribution to the structural prediction of classes of molecules that are poorly represented in spectral libraries. The imaging of small molecules by MALDI-MS grants spatial mapping of in situ NPs, allowing a better understanding of their function and distribution. As technological advances in terms of equipment, images and MS/MS data can be simultaneously generated, allowing the direct annotation of molecules. Additionally, the introduction of a third dimension by ionic mobility reveals the possibility of single-cell analysis by spatial resolution. This perspective article by Lopes and da Silva shines light on these significant issues and all the opportunities ahead of us in NP research. The original article of this Research Topic by Queiroz et al. is about the chemical profile of organic apolar and polar extracts from leaves and stems of Alzatea verticillata Ruiz & Pav. (Alzateaceae). By semipreparative LC, twelve compounds were isolated in a milligram scale, of which three were unknown. The structure elucidation of the isolated compounds was carried out based on NMR and HRMS analyses. The previously undescribed compounds included a dimeric lactone, dimethyl anemonin, and two unusual dimeric diphenyl cyclobutane dicarboxylic acids (β-truxinic derivatives). The X-ray crystallography of the new dimeric lactone revealed it as an (S,S), (R,R) racemate. This article provides a biogenetic proposal that is in line with the obtained racemate. Additionally, non-target LC-HRMS data OPEN ACCESS","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"60 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123123630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In situ spatiotemporal mapping of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitor in pineapple (Ananas comosus) fruit tissue by MALDI mass spectrometry imaging","authors":"A. Suarez, Angel Ann B. Juanillo, D. C. D. Sison, J. I. Orajay, Maria Bella B. Javier, Diane Monique S. Baladjay, Yu-Liang Yang, J. Saludes, Doralyn S. Dalisay","doi":"10.3389/fntpr.2023.1160541","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1160541","url":null,"abstract":"Pineapple (Ananas comosus) fruit is a functional food that has become a part of healthy diets worldwide due to its nutrition and health benefits. Given this concept, the potential anti-hypercholesterolemic activity of pineapple fruit was assessed using in vitro HMG-CoA reductase (HMGCR) inhibition assay. Our findings show that pineapple fruit (PAF) extract showed HMGCR inhibition activity. These findings led to partial purification of PAF extract by gel filtration chromatography (GFC) whereby fraction PAF 06 exhibited 100.00% HMGCR inhibition at 10 mg/mL. Matrix assisted laser desorption ionization (MALDI) mass spectrometry profiling, HRMS, MS/MS, and dereplication identified N1, N10-diferuloylspermidine as potential HMGCR inhibitor in pineapple fruit. The MALDI mass spectrometry imaging (MSI) enabled the in situ spatiotemporal mapping of the HMGCR inhibitor, N1, N10-diferuloylspermidine, in the pineapple fruit tissue, with localization concentrated mainly in the tissue near the peel/shell and a gradual decrease towards the flesh and ovary. The MALDI MSI provided the first evidence of in situ spatial localization of N1, N10-diferuloylspermidine, a potential HMGCR inhibitor in pineapple while maintaining the cellular and structural features of the fruit tissues.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117159436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical study of Alzatea verticillata, the sole species belonging to the Alzateaceae family","authors":"Marcos Marçal Ferreira Queiroz, R. Huber, L. Marcourt, L. Guénée, Pierre-Marie Allard, Adriano Rutz, Louis-Félix Nothias, Concetta Carlotta De Ruvo, J. Kissling, Mahabir P. Gupta, Emerson Ferreira Queiroz, J. Wolfender","doi":"10.3389/fntpr.2023.1147195","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1147195","url":null,"abstract":"Alzatea verticillata Ruiz & Pav. (Alzateaceae) is a tropical tree from Central and South America. It is the only living species of Alzatea genus and the Alzateaceae family, all others being extinct. With the aim to investigate the possibility to find unusual natural products, the chemical content of the dichloromethane and methanolic extracts (stems and leaves) of A. verticillata have been investigated. Apolar and polar extracts were purified by semi-preparative HPLC using appropriate stationary phase columns allowing the isolation of 12 compounds: walterolactone B (2) walterolactone A/B β-D-pyranoglucoside (3), gallic acid (4), caffeic acid 4-O-β-D-glucopyranoside (6), walterolactone A/B 6-O-gallate-β-D-glucopyranoside (8), caffeic acid (9), 8-desmethylsideroxylin (11), sideroxylin (12) and 7,7′-bis(3,4-dihydroxyphenyl)-8,8′-cyclobutanedicarboxylic acid (7). Three isolated compounds are natural products described here for the first time: dimethyl-anemonin (1) and two β-truxinic acid derivatives (rel-(7S, 8R, 7′R, 8′S)-7,7′-bis(4-glucosyloxy-3-hydroxyphenyl)-8,8′-cyclobutane dicarboxylic acid (5) and rel-(7S, 8R, 7′R, 8′S)-7,7′-bis(4-glucosyloxy-3-hydroxyphenyl)-8,8′-cyclobutane-9-methyl dicarboxylic acid (10). The structures of the isolated compounds were elucidated by NMR and HRMS. The structure of compound 1 was confirmed by X-ray crystallography. A MS-based metabolite analysis of the A. verticillata extracts revealed additional truxinic acid derivatives that were putatively annotated with the help of feature-based molecular network. The presence of phenolic compounds such as truxinic acid derivatives could explain the traditional use of this plant as these compounds are known to possess anti-inflammatory and anti-nociceptive properties.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117105970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From structural determination of natural products in complex mixtures to single cell resolution: Perspectives on advances and challenges for mass spectrometry","authors":"N. Lopes, Ricardo Roberto da Silva","doi":"10.3389/fntpr.2023.1109557","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1109557","url":null,"abstract":"The search for new Natural Products is one of the oldest interests for research in chemistry. The history of this discipline is very prolific, from its initial uses as medicine to advanced omics strategies to understand the mechanics of biological controls in living cells. The discoveries of morphine, penicillin, taxol and many other natural products revolutionized human health. During the last 40 years, excellent reviews published by Dr. David Newman and Dr. Gordon Crag have revealed that the pharmaceutical industry’s research into natural products has lost some of its steam. Nevertheless, new natural products for antimicrobials, antifungals, and anticancer drugs remained the main alternative. Furthermore, research institutes have seen great vigor, and several startup companies have emerged worldwide, seeking therapeutic alternatives based in natural products. Innovations on spectrometric hardware, allowing broader coverage of chemical classes and spatial mapping, and in software, enabling the interpretation of large volumes of data, afforded a renewed interest in natural products and are considered the most important enabling technology for the new companies. In this perspective article we give some historical context to exciting developments, on software and spatial resolution, that promise to pave the way for a bright future of Natural Products research.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115000513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning in computational NMR-aided structural elucidation","authors":"Iván Cortés, Cristina Cuadrado, A. Hernández Daranas, Ariel M. Sarotti","doi":"10.3389/fntpr.2023.1122426","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1122426","url":null,"abstract":"Structure elucidation is a stage of paramount importance in the discovery of novel compounds because molecular structure determines their physical, chemical and biological properties. Computational prediction of spectroscopic data, mainly NMR, has become a widely used tool to help in such tasks due to its increasing easiness and reliability. However, despite the continuous increment in CPU calculation power, classical quantum mechanics simulations still require a lot of effort. Accordingly, simulations of large or conformationally complex molecules are impractical. In this context, a growing number of research groups have explored the capabilities of machine learning (ML) algorithms in computational NMR prediction. In parallel, important advances have been made in the development of machine learning-inspired methods to correlate the experimental and calculated NMR data to facilitate the structural elucidation process. Here, we have selected some essential papers to review this research area and propose conclusions and future perspectives for the field.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114156258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An overview of the most threating diseases that affect worldwide citriculture: Main features, diagnose, and current control strategies","authors":"Hellen Bertoletti Barbieri, Laura Soler Fernandes, J. G. Pontes, Alan K. Pereira, T. Fill","doi":"10.3389/fntpr.2023.1045364","DOIUrl":"https://doi.org/10.3389/fntpr.2023.1045364","url":null,"abstract":"Citriculture has been one of the most important agricultural activities worldwide. Brazil is among the five major citrus producers in the world, together with China, the European Union (EU), the United States, and Mexico. Together, these five groups are responsible for about 50% of the global citrus fruit production and this industrial segment is responsible for generating direct and indirect jobs. However, several citric diseases such as citrus canker, huanglongbing, citrus variegated chlorosis, and citrus black spot have been associated with annual losses of tons of fruits and orange trees impacting the global economy for decades. Citrus canker is caused by the Gram-negative bacteria Xanthomonas citri subsp. citri. and is associated with symptoms such as the formation of chlorotic rings in the leaves, stems, and fruits. Huanglongbing (HLB) is mainly associated with the Gram-negative bacteria Candidatus Liberibacter spp. and its main symptoms are the appearance of yellowish branches and deformed small leaves with yellowish spots. Citrus variegated chlorosis (CVC) is associated with the bacterium Xylella fastidiosa and causes chlorotic spots with irregular edges on leaves and deformation of new leaves. Citrus black spot (CBS) is caused by the fungus Phyllosticta citricarpa and generates lesions on fruits and reddish-brown leaf lesions. Since citrus is important for global agriculture, the current review addresses the main features of these important diseases including their symptoms and transmission, as well as the diagnosis and control strategies that have been studied so far for application in the field.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114635663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational methods and points for attention in absolute configuration determination","authors":"Huajie Zhu, Yufang Wang, L. Nafie","doi":"10.3389/fntpr.2022.1086897","DOIUrl":"https://doi.org/10.3389/fntpr.2022.1086897","url":null,"abstract":"With the rapid development of high performance computers and computational methods, including software, an increasing number of experimental chemists have tried to use computational methods such as optical rotation (OR, including the matrix model), optical rotatory dispersion (ORD), electronic circular dichroism (ECD or CD), vibrational circular dichroism (VCD), and magnetic shielding constants—nuclear magnetic resonance (NMR)—to explain and/or assign absolute configuration (AC) for various compounds. Such reports in the field of natural products have increased dramatically. However, every method has its range of application. This leads, in some cases, to incorrect conclusions by researchers who are not familiar with these methods. In this review, we provide experimental chemists and researchers with more computational details and suitable suggestions, and especially hope that this experience may help readers avoid computational pitfalls. Finally, we discuss the use of simplified models to replace original complex structures with a long side chain. The fundamental basis for using models to represent complex chiral compounds, such as in OR calculations, is the existence of conformation pairs with near canceling conformer contributions that justify the use of models rather than the original compounds. Using examples, we here introduce the transition state (TS) calculation, which may benefit readers in this area for use and mastery for their AC study. This review will summarize the general concepts involved in the study of AC determinations.","PeriodicalId":159634,"journal":{"name":"Frontiers in Natural Products","volume":"119 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122471431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}