Natural Product Reports最新文献

{"title":"Therapeutic vulnerabilities of cancer stem cells and effects of natural products","authors":"Keighley N. Reisenauer, Jaquelin Aroujo, Yongfeng Tao, Santhalakshmi Ranganathan, Daniel Romo and Joseph H. Taube","doi":"10.1039/D3NP00002H","DOIUrl":"https://doi.org/10.1039/D3NP00002H","url":null,"abstract":"<p>Covering: 1995 to 2022</p><p>Tumors possess both genetic and phenotypic heterogeneity leading to the survival of subpopulations post-treatment. The term cancer stem cells (CSCs) describes a subpopulation that is resistant to many types of chemotherapy and which also possess enhanced migratory and anchorage-independent growth capabilities. These cells are enriched in residual tumor material post-treatment and can serve as the seed for future tumor re-growth, at both primary and metastatic sites. Elimination of CSCs is a key goal in enhancing cancer treatment and may be aided by application of natural products in conjunction with conventional treatments. In this review, we highlight molecular features of CSCs and discuss synthesis, structure–activity relationships, derivatization, and effects of six natural products with anti-CSC activity.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3799730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A chemoinformatic analysis on natural glycosides with respect to biological origin and structural class†","authors":"Yinliang Chen, Yi Liu, Nianhang Chen, Yuting Jin, Ruofei Yang, Hucheng Yao and De-Xin Kong","doi":"10.1039/D2NP00089J","DOIUrl":"https://doi.org/10.1039/D2NP00089J","url":null,"abstract":"<p>Covering: up to 2022</p><p>16.19% of reported natural products (NPs) in the Dictionary of Natural Products (DNP) are glycosides. As one of the most important NPs' structural modifications, glycosylation can change the NPs' polarity, making the aglycones more amphipathic. However, until now, little is known about the general distribution profile of the natural glycosides in different biological sources or structural types. The reason, structural or species preferences of the natural glycosylation remain unclear. In this highlight, chemoinformatic methods were employed to analyze the natural glycosides from DNP, the most comprehensively annotated NP database. We found that the glycosylation ratios of NPs from plants, bacteria, animals and fungi decrease successively, which are 24.99%, 20.84%, 8.40% and 4.48%, respectively. Echinoderm-derived NPs (56.11%) are the most frequently glycosylated, while those produced by molluscs (1.55%), vertebrates (2.19%) and Rhodophyta (3.00%) are the opposite. Among the diverse structural types, a large proportion of steroids (45.19%), tannins (44.78%) and flavonoids (39.21%) are glycosides, yet aminoacids and peptides (5.16%), alkaloids (5.66%) are comparatively less glycosylated. Even within the same biological source or structural type, their glycosylation rates fluctuate drastically between sub- or cross-categories. The substitute patterns of flavonoid and terpenoid glycosides and the most frequently glycosylated scaffolds were identified. NPs with different glycosylation levels occupy different chemical spaces of physicochemical property and scaffold. These findings could help us to interpret the preference of NPs' glycosylation and investigate how NP glycosylation could aid NP-based drug discovery.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24849494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finding activity through rigidity: syntheses of natural products containing tricyclic bridgehead carbon centers","authors":"Zhi Xu, Xin Li, John A. Rose and Seth B. Herzon","doi":"10.1039/D3NP00008G","DOIUrl":"https://doi.org/10.1039/D3NP00008G","url":null,"abstract":"<p>Covering: up to 2022</p><p>Tricyclic bridgehead carbon centers (TBCCs) are a synthetically challenging substructure found in many complex natural products. Here we review the syntheses of ten representative families of TBCC-containing isolates, with the goal of outlining the strategies and tactics used to install these centers, including a discussion of the evolution of the successful synthetic design. We provide a summary of common strategies to inform future synthetic endeavors.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2023/np/d3np00008g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3799729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction to volatile natural products","authors":"Stefan Schulz","doi":"10.1039/D3NP90015K","DOIUrl":"https://doi.org/10.1039/D3NP90015K","url":null,"abstract":"<p >A graphical abstract is available for this content</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3896250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural diversity, hypothetical biosynthesis, chemical synthesis, and biological activity of Ganoderma meroterpenoids","authors":"Xing-Rong Peng, Sybille B. Unsicker, Jonathan Gershenzon and Ming-Hua Qiu","doi":"10.1039/D3NP00006K","DOIUrl":"https://doi.org/10.1039/D3NP00006K","url":null,"abstract":"<p>Covering: 2018 to 2022</p><p>Meroterpenoids found in fungal species of the genus <em>Ganoderma</em> and known as <em>Ganoderma</em> meroterpenoids (GMs) are substances composed of a 1,2,4-trisubstituted benzene and a polyunsaturated side chain. These substances have attracted the attention of chemists and pharmacologists due to their diverse structures and significant bioactivity. In this review, we present the structures and possible biosynthesis of representative GMs newly found from 2018 to 2022, as well as chemical synthesis and biological activity of some interesting GMs. We propose for the first time a plausible biosynthetic pathway for GMs, which will certainly motivate further research on the biosynthetic pathway in <em>Ganoderma</em> species, as well as on chemical synthesis of GMs as important bioactive compounds for the purpose of drug development.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3799728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-Adenosylmethionine: more than just a methyl donor","authors":"Yu-Hsuan Lee, Daan Ren, Byungsun Jeon and Hung-wen Liu","doi":"10.1039/D2NP00086E","DOIUrl":"https://doi.org/10.1039/D2NP00086E","url":null,"abstract":"<p>Covering: from 2000 up to the very early part of 2023</p><p> <em>S</em>-Adenosyl-<small>L</small>-methionine (SAM) is a naturally occurring trialkyl sulfonium molecule that is typically associated with biological methyltransfer reactions. However, SAM is also known to donate methylene, aminocarboxypropyl, adenosyl and amino moieties during natural product biosynthetic reactions. The reaction scope is further expanded as SAM itself can be modified prior to the group transfer such that a SAM-derived carboxymethyl or aminopropyl moiety can also be transferred. Moreover, the sulfonium cation in SAM has itself been found to be critical for several other enzymatic transformations. Thus, while many SAM-dependent enzymes are characterized by a methyltransferase fold, not all of them are necessarily methyltransferases. Furthermore, other SAM-dependent enzymes do not possess such a structural feature suggesting diversification along different evolutionary lineages. Despite the biological versatility of SAM, it nevertheless parallels the chemistry of sulfonium compounds used in organic synthesis. The question thus becomes how enzymes catalyze distinct transformations <em>via</em> subtle differences in their active sites. This review summarizes recent advances in the discovery of novel SAM utilizing enzymes that rely on Lewis acid/base chemistry as opposed to radical mechanisms of catalysis. The examples are categorized based on the presence of a methyltransferase fold and the role played by SAM within the context of known sulfonium chemistry.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24849497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine indole alkaloid diversity and bioactivity. What do we know and what are we missing?†","authors":"Darren C. Holland and Anthony R. Carroll","doi":"10.1039/D2NP00085G","DOIUrl":"10.1039/D2NP00085G","url":null,"abstract":"<p>Covering: marine indole alkaloids (<em>n</em> = 2048) and their reported bioactivities up to the end of 2021</p><p>Despite increasing numbers of marine natural products (MNPs) reported each year, most have only been examined for cytotoxic, antibacterial, and/or antifungal biological activities with the majority found to be inactive in these assays. In this context, why are natural products continuing to be examined in assays they are unlikely to show significant activity in, and what targets might be more useful for expanding knowledge of their biologically relevant chemical space? We have undertaken a meta-analysis of the biological activities for 2048 marine indole alkaloids (MIAs), a diverse sub-class of MNPs reported up to the end of 2021, and this has highlighted that the bioactivity potentials for up to 86% of published MIAs remains underexplored and/or undefined. Although most published MIAs are not cytotoxic or antimicrobial, there is a continued focus on using these assays to evaluate new structurally related analogues. Using cheminformatics analyses, the chemical diversity of the 2048 MIAs were clustered using fragment based fingerprints and their reported bioactivity potency towards specific disease targets was assessed for structure activity trends. These analyses showed that there are groups of MIAs that possess potent and diverse activities and that many analogues, previously tested only in cellular toxicity assays, could be better exploited to generate structure activity relationships associated with leads to treat emerging diseases. A collection of indole drug and drug-lead structures from non-natural sources were also incorporated into the dataset providing complementary bioactivity profiles that were further used to predict underexplored areas of potential new activity and to better direct future testing of MIAs. Our findings clearly suggest the biological evaluation of MIAs continues to be conducted on a narrow range of bioassays and disease targets, and that shifting the focus to non-toxic disease targets should provide expanded knowledge of biologically relevant chemical space aimed at maximising the potential of MIAs for drug discovery.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10705567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction to engineering the biosynthesis of fungal natural products","authors":"Russell J. Cox and Tobias A. M. Gulder","doi":"10.1039/D2NP90047E","DOIUrl":"https://doi.org/10.1039/D2NP90047E","url":null,"abstract":"<p >Filamentous fungi are highly diverse eukaryotes that inhabit all known ecosystems on earth. Estimates suggest that more than 2 × 10<small>⁶</small> species are likely to exist, and analyses of typical fungal genomes suggest they harbour around 50 biosynthetic gene clusters on average. The biosynthetic potential of these organisms is thus vast. Fungi produce all the main classes of secondary metabolites, and numerous hybrid compounds. Many are highly useful in medicine such as the ‘classic’ special metabolites penicillins, cephalosporins, statins and mycophenolic acid, and new antimicrobial agents such as the pleuromutilins and enfumafungins that overcome specific patterns of resistance. Fungi differentiated from bacteria more than a billion years ago, so there has been plenty of time for uniquely fungal biosynthetic systems to evolve.</p>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3896253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The volatile chemistry of orchid pollination","authors":"James Perkins ,&nbsp;Tobias Hayashi ,&nbsp;Rod Peakall ,&nbsp;Gavin R. Flematti ,&nbsp;Björn Bohman","doi":"10.1039/d2np00060a","DOIUrl":"10.1039/d2np00060a","url":null,"abstract":"<div><p>Covering: up to September 2022</p><p>Orchids are renowned not only for their diversity of floral forms, but also for their many and often highly specialised pollination strategies. Volatile semiochemicals play a crucial role in the attraction of a wide variety of insect pollinators of orchids. The compounds produced by orchid flowers are as diverse as the pollinators they attract, and here we summarise some of the chemical diversity found across orchid taxa and pollination strategies. We focus on compounds that have been experimentally demonstrated to underpin pollinator attraction. We also highlight the structural elucidation and synthesis of a select subset of important orchid pollinator attractants, and discuss the ecological significance of the discoveries, the gaps in our current knowledge of orchid pollination chemistry, and some opportunities for future research in this field.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2023/np/d2np00060a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3896255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future antimalarials from Artemisia? A rationale for natural product mining against drug-refractory Plasmodium stages","authors":"Alexandre Maciuk ,&nbsp;Dominique Mazier ,&nbsp;Romain Duval","doi":"10.1039/d3np00001j","DOIUrl":"10.1039/d3np00001j","url":null,"abstract":"<div><p>Covering: up to 2023</p><p>Infusions of the plants <em>Artemisia annua</em> and <em>A. afra</em> are gaining broad popularity to prevent or treat malaria. There is an urgent need to address this controversial public health question by providing solid scientific evidence in relation to these uses. Infusions of either species were shown to inhibit the asexual blood stages, the liver stages including the hypnozoites, but also the sexual stages, the gametocytes, of <em>Plasmodium</em> parasites. Elimination of hypnozoites and sterilization of mature gametocytes remain pivotal elements of the radical cure of <em>P. vivax</em>, and the blockage of <em>P. vivax</em> and <em>P. falciparum</em> transmission, respectively. Drugs active against these stages are restricted to the 8-aminoquinolines primaquine and tafenoquine, a paucity worsened by their double dependence on the host genetic to elicit clinical activity without severe toxicity. Besides artemisinin, these <em>Artemisia</em> spp. contain many natural products effective against <em>Plasmodium</em> asexual blood stages, but their activity against hypnozoites and gametocytes was never investigated. In the context of important therapeutic issues, we provide a review addressing (i) the role of artemisinin in the bioactivity of these <em>Artemisia</em> infusions against specific parasite stages, <em>i.e.</em>, alone or in association with other phytochemicals; (ii) the mechanisms of action and biological targets in <em>Plasmodium</em> of <em>ca.</em> 60 infusion-specific <em>Artemisia</em> phytochemicals, with an emphasis on drug-refractory parasite stages (<em>i.e.</em>, hypnozoites and gametocytes). Our objective is to guide the strategic prospecting of antiplasmodial natural products from these <em>Artemisia</em> spp., paving the way toward novel antimalarial “hit” compounds either naturally occurring or <em>Artemisia</em>-inspired.</p></div>","PeriodicalId":94,"journal":{"name":"Natural Product Reports","volume":null,"pages":null},"PeriodicalIF":11.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3812187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}