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This document is a correction notice for an article titled "Metabolism characterization and toxicity of N-hydap, a marine candidate drug for lung cancer therapy by LC-MS method" published in the journal Natural Products & Bioprospecting. The correction addresses mistakes in the original article, specifically related to the bioavailability and distribution of N-hydap. The corrected information states that N-hydap has a favorable bioavailability of 24.0% and exhibits a higher distribution in the lungs, making it effective against small cell lung cancer. The correction also includes updates to the graphical abstract and a table presenting pharmacokinetic parameters. The corrected article concludes that N-hydap, with its improved bioavailability, is a promising candidate for anti-small cell lung cancer therapy. [Extracted from the article]

Our study of the secondary metabolites of coral-associated fungi produced a valuable and extra-large chemical database. Many of them exhibit strong biological activity and can be used for promising drug lead compounds. Serving as an epitome of the most promising compounds, which take the ultra-new skeletons and/or remarkable bioactivities, this review presents an overview of new compounds and bioactive compounds isolated from coral-associated fungi, covering the literature from 2010 to 2021. Its scope included 423 metabolites, focusing on the bioactivity and structure diversity of these compounds. According to structure, these compounds can be roughly classified as terpenes, alkaloids, peptides, aromatics, lactones, steroids, and other compounds. Some of them described in this review possess a wide range of bioactivities, such as anticancer, antimicrobial, antifouling, and other activities. This review aims to provide some significant chemical and/or biological enlightenment for the study of marine natural products and marine drug development in the future. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Natural products derived from marine microorganisms have been received great attention as a potential source of new compound entities for drug discovery. The unique marine environment brings us a large group of halogen‐containing natural products with abundant biological functionality and good drugability. Meanwhile, biosynthetically halogenated reactions are known as a significant strategy used to increase the pharmacological activities and pharmacokinetic properties of compounds. Given that a tremendous increase in the number of new halogenated compounds from marine microorganisms in the last five years, it is necessary to summarize these compounds with their diverse structures and promising bioactivities. In this review, we have summarized the chemistry, biosynthesis (related halogenases), and biological activity of a total of 316 naturally halogenated compounds from marine microorganisms covering the period of 2015 to May 2021. Those reviewed chlorinated and brominated compounds with the ratio of 9 : 1 were predominantly originated from 36 genera of fungi (62%) and 9 bacterial strains (38%) with cytotoxic, antibacterial, and enzyme inhibitory activities, structural types of which are polyketides (38%), alkaloids (27%), phenols (11%), and others. This review would provide a plenty variety of promising lead halogenated compounds for drug discovery and inspire the development of new pharmaceutical agents. [ABSTRACT FROM AUTHOR]

The deep sea has been proven to be a great treasure for structurally unique and biologically active natural products in the last two decades. Cold seeps and hydrothermal vents, as typical representatives of deep-sea extreme environments, have attracted more and more attention. This review mainly summarizes the natural products of marine animals, marine fungi, and marine bacteria derived from deep-sea cold seeps and hydrothermal vents as well as their biological activities. In general, there were 182 compounds reported, citing 132 references and covering the literature from the first report in 1984 up to March 2022. The sources of the compounds are represented by the genera Aspergillus sp., Penicillium sp., Streptomyces sp., and so on. It is worth mentioning that 90 of the 182 compounds are new and that almost 60% of the reported structures exhibited diverse bioactivities, which became attractive targets for relevant organic synthetic and biosynthetic studies. [ABSTRACT FROM AUTHOR]

Nuclear receptors (NRs) are a superfamily of transcription factors induced by ligands and also function as integrators of hormonal and nutritional signals. Among NRs, the liver X receptors (LXRs) and farnesoid X receptor (FXR) have been of significance as targets for the treatment of metabolic syndrome-related diseases. In recent years, natural products targeting LXRs and FXR have received remarkable interests as a valuable source of novel ligands encompassing diverse chemical structures and bioactive properties. This review aims to survey natural products, originating from terrestrial plants and microorganisms, marine organisms, and marine-derived microorganisms, which could influence LXRs and FXR. In the recent two decades (2000–2020), 261 natural products were discovered from natural resources such as LXRs/FXR modulators, 109 agonists and 38 antagonists targeting LXRs, and 72 agonists and 55 antagonists targeting FXR. The docking evaluation of desired natural products targeted LXRs/FXR is finally discussed. This comprehensive overview will provide a reference for future study of novel LXRs and FXR agonists and antagonists to target human diseases, and attract an increasing number of professional scholars majoring in pharmacy and biology with more in-depth discussion. [ABSTRACT FROM AUTHOR]

Context: Epidioxy sterols and sterols with special side chains, such as hydroperoxyl sterols, usually obtained from marine natural products, are attractive for bioactivities. Objective: To isolate and screen bioactive and special sterols from China Sea invertebrates. Materials and methods: Two hydroperoxyl sterols ( 1 and 2) from the sponge Xestospongia testudinaria Lamarck (Petrosiidae), three epidioxy sterols ( 3- 5) from the sea urchin Glyptocidaris crenularis A. Agassiz (Glyptocidaridae), sponge Mycale sp. (Mycalidae) and gorgonian Dichotella gemmacea Milne Edwards and Haime (Ellisellidae) and an unusual sterol with 25-acetoxy-19-oate ( 6) also from D. gemmacea were obtained and identified. Using high-throughput screening, their bioactivities were tested toward Forkhead box O 3a (Foxo3a), 3-hydroxy-3-methylglutaryl CoA reductase gene fluorescent protein (HMGCR-GFP), nuclear factor kappa B (NF-κB) luciferase, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), protein-tyrosine phosphatase 1B (PTP1B), mitochondrial membrane permeabilization (MMP) and adenosine monophosphate-activated protein kinase. Results: Their structures were determined by comparing their nuclear magnetic resonance data with those reported in the literature. Three epidioxy sterols ( 3- 5) showed inhibitory activities toward Foxo3a, HMGCR-GFP and NF-κB-luciferase with the IC50 values 4.9-6.8 μg/mL. The hydroperoxyl sterol 29-hydroperoxystigmasta-5,24(28)-dien-3-ol ( 2) had diverse inhibitory activities against Foxo3a, HMGCR-GFP, NF-κB-luciferase, PGC-1α, PTP1B and MMP, with IC50 values of 3.8-19.1 μg/mL. Discussion and conclusion: The bioactivities of 3- 5 showed that 5α,8α-epidioxy is the active group. Otherwise, the most plausible biosynthesis pathway for 1 and 2 in sponge involves the abstraction of an allylic proton by an activated oxygen, such as O2, along with migration of carbon-carbon double bond. Therefore, the bioactive and unstable steroid should be biosynthesized in sponge under a special ecological environment to act as a defensive strategy against invaders. [ABSTRACT FROM AUTHOR]

[Display omitted] • A number of natural axinelline A analogs 5a - 12 g were synthesized. • The COX-1/-2 inhibitory activity of compounds 5a - 12 g were evaluated. • The molecular docking study between compound 5e and COX-2 enzyme was conducted. • The in vitro and in vivo anti-inflammatory activity of compound 5e was investigated. Marine natural products continue to hold great promise as potential candidates for the discovery of anti-inflammatory drug. In our previous investigation, we successfully synthesized axinelline A, a naturally occurring cyclooxygenase-2 (COX-2) inhibitor, as a promising anti-inflammatory lead compound. This study was to discover novel COX inhibitors with balanced inhibition, aiming to mitigate the severe adverse effects through further structural modification of axinelline A. Of the synthetic derivatives, compound 5e showed highest COX-2 inhibitory activity and balanced COX inhibition (IC 50 = 1.74 µM; selectivity ((IC 50 (COX-1)/IC 50 (COX-2) = 16.32). The in vitro anti-inflammatory results indicated that 5e effectively suppressed the expression of pro-inflammatory mediators via the NF-κB signaling pathway rather than the MAPK signaling pathway. The in vivo ulcerative colitis assay demonstrated 5e significantly ameliorated the histological damages and showed strong protection against DSS-induced acute colitis. Therefore, our findings suggest that compound 5e exhibits potential as a promising anti-inflammatory agent with attenuated colitis-related adverse effects. [ABSTRACT FROM AUTHOR]

The emergence of drug-resistant Vibrio poses a serious threat to aquaculture and human health, thus there is an urgent need for the discovery of new related antibiotics. Given that marine microorganisms (MMs) are evidenced as important sources of antibacterial natural products (NPs), great attention has been gained to the exploration of potential anti- Vibrio agents from MMs. This review summarizes the occurrence, structural diversity, and biological activities of 214 anti- Vibrio NPs isolated from MMs (from 1999 to July 2022), including 108 new compounds. They were predominantly originated from marine fungi (63%) and bacteria (30%) with great structural diversity, including polyketides, nitrogenous compounds, terpenoids, and steroids, among which polyketides account for nearly half (51%) of them. This review will shed light on the development of MMs derived NPs as potential anti- Vibrio lead compounds with promising applications in agriculture and human health. [Display omitted] • Anti- Vibrio natural products from marine microorganisms were summarized, while polyketides are main structural type (51%). • Marine fungi (63%) and bacteria (30%) are predominant sources of anti- Vibrio natural products. • This review highlighted the potential development of these natural products as anti- Vibrio lead compounds. [ABSTRACT FROM AUTHOR]

Ochrathinols A and B ((±)- 1 and (±)- 2), two undescribed sulfur-containing racemates, and ochracids A and B (3 and 4), two unprecedented pyrrolizidine alkaloids, were isolated from an Antarctic soil-derived fungus Aspergillus ochraceopetaliformis SCSIO 05702. Their structures including absolute configurations were determined through extensive spectroscopic analysis, chiral-phase HPLC analysis, quantum ECD calculations, and X-ray single-crystal diffraction. Ochrathinols A and B are unprecedented sulfur natural products featuring a novel 3-methylhexahydro-2 H -cyclopenta [b]thiophene core. Interestingly, ochrathinol A ((±)- 1) outstandingly suppressed the release of LPS-induced IL-1 β , IL-6, and TNF- α inflammatory cytokines with concentration of 10 μM and alleviated the unbalanced NAD+/NADH ratio caused by LPS in RAW264.7 macrophages. [Display omitted] • Ochrathinols A and B ((±)- 1 and (±)- 2) were isolated from an Antarctic fungus. • Ochrathinols A and B are unprecedented sulfur natural products featuring a novel 3-methylhexahydro-2 H -cyclopenta [b]thiophene core. • Their absolute configurations were elucidated by ECD calculations and X-ray single-crystal diffraction. • Ochrathinol A ((±)- 1) exhibited potent anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel terpestacin derivatives with l -amino acid residue were designed and synthesized. • Compounds 5 , 11 , 13 , 15 showed good activities against U87MG-derived GSCs. • 13 and 15 had stronger activities than terpestacin and the positive control A1938. • 13 and 15 can be further developed for new anticancer agents against GBM. • Our syntheses of terpestacin derivatives are easy and convenient. Based on the natural product terpestacin, seventeen derivatives (1 – 17) with various l -amino acid side chains were designed and synthesized. Their anticancer activities against U87MG-derived glioblastoma stem cells (GSCs) were evaluated, and compounds 5 , 11 , 13 and 15 showed strong abilities to inhibit the proliferation (IC 50 = 2.8–6.9 μM) and tumorsphere formation of GSCs. Besides, compounds 13 and 15 could effectively induce apoptosis and significantly inhibit the invasion of GSCs (95 and 97 % inhibition, respectively, at 2.5 μM). The levels of CD133 marker in GSCs also decreased in dose-dependent manners after the treatment of these active compounds. Compared to terpestacin and the positive control A1938, our derivatives showed stronger activities and compounds 13 and 15 are promising candidates for further development as anticancer agents by targeting GSCs. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is an aggressive and exceptionally fatal disease. Unlike non- small cell lung cancer (NSCLC), no targetable genetic driver events have been identified in SCLC to date. Here, we investigate the function of RAR-related orphan receptor gamma (RORγ) and identified the anti-cancer activity of its natural inhibitor against SCLC and illustrate the underlying mechanism. We show that RORγ depletion affected cell growth both in 2-D cell proliferation and 3-D organoids formation. Natural marine product N -hydroxyapiosporamide (N -hydap) directly bound to RORγ and inhibited its transcriptional activity, leading to the blocking of transmission process of RORγ signaling. Gene expression profiling analysis revealed that N -hydap reprograms neuroendocrine fate via inhibiting RORγ activity in SCLC. Chromatin immunoprecipitation analysis showed that N -hydap strongly reduced RORγ occupancy and transcriptional activation-linked histone marks H3K27ac on the promoter and/or enhancer sites of neurogenesis markers gene including aurora kinase a (AURKA), delta like canonical Notch ligand 3 (DLL3) and tubulin beta 3 class III (TUBB3). Therapeutically, N -hydap exhibited a strong inhibitory effect on tumor growth and did not show significant toxicity in SCLC mice xenograft models. Taken together, RORγ could be an attractive target for SCLC and thus N -hydap can be a promising therapeutic drug candidate for SCLC by inhibiting the RORγ activation. [Display omitted] • RORγ represents a potential therapeutic target in SCLC. • Natural product N -hydap was identified as a novel and potent RORγ inhibitor. • RORγ reprograms neuroendocrine fate of SCLC cells both in vitro and in vivo. • N -hydap can be a promising therapeutic drug candidate for SCLC. [ABSTRACT FROM AUTHOR]

The mangrove forests are a complex ecosystem, and the microbial communities in mangrove sediments play a critical role in the biogeochemical cycles of mangrove ecosystems. Mangrove sediments-derived microbes (MSM), as a rich reservoir of natural product diversity, could be utilized in the exploration of new antibiotics or drugs. To understand the structural diversity and bioactivities of the metabolites of MSM, this review for the first time provides a comprehensive overview of 519 natural products isolated from MSM with their bioactivities, up to 2021. Most of the structural types of these compounds are alkaloids, lactones, xanthones, quinones, terpenoids, and steroids. Among them, 210 compounds are obtained from bacteria, most of which are from Streptomyces , while 309 compounds are from fungus, especially genus Aspergillus and Penicillium. The pharmacological mechanisms of some representative lead compounds are well studied, revealing that they have important medicinal potentials, such as piericidins with anti-renal cell cancer effects, azalomycins with anti-MRSA activities, and ophiobolins as antineoplastic agents. The biosynthetic pathways of representative natural products from MSM have also been summarized, especially ikarugamycin, piericidins, divergolides, and azalomycins. In addition, the total synthetic strategies of representative secondary metabolites from MSM are also reviewed, such as piericidin A and borrelidin. This review provides an important reference for the research status of natural products isolated from MSM and the lead compounds worthy of further development, and reveals that MSM have important medicinal values and are worthy of further development. [Display omitted] • Overview of 519 NPs from mangrove sediments-derived microbes up to 2021. • 70% of those NPs displayed a wide range of bioactivities. • Pharmacology, biosynthesis, and total synthesis of representative NPs were summarized. • NPs from mangrove sediments-derived microbes are worthy of further drug development. [ABSTRACT FROM AUTHOR]

Abstract: Our continued investigation on the South China Sea gorgonian Dichotella gemmacea led to the isolation of 16 new briarane-type diterpenoids, dichotellides F–U (1–16), along with 18 known analogues (17–34). Their structures were determined by MS, 1D and 2D NMR spectra analyses and by comparison with those reported in literature. The absolute configuration of 15 was confirmed by single-crystal X-ray diffraction data. The antifouling test showed that compounds 3, 4, 6–11, 16, and 23 had potent antifouling activities at nontoxic concentrations with EC50 values of 4.1, 1.82, 6.3, 7.6, 4.6, 1.2, 5.6, 0.79, 2.0, and 0.2 μg/mL, respectively. [Copyright &y& Elsevier]

Terminal allylic alcohols are important motifs in natural products, and also key intermediates/precursors in numerous novel reaction transformations. In this study, enabled by a bifunctional ligand featuring a basic amino group, a gold-catalyzed hydroarylation of terminal unactivated propargylic alcohols with heteroareneboronic acids has been first established, and efficiently affords various terminal aryl-substituted allylic alcohols with moderate to high yields under mild conditions. Image 1 • Novel gold-catalyzed hydroarylation of terminal alkynols has been established. • This hydroarylation is enabled by a bifunctional ligand with a remote amino group. • New aryl-substituted allylic alcohols have been formed in moderate to high yields. • Low load of catalyst makes this strategy more affordable. • Mild reaction conditions makes this strategy more applicable. [ABSTRACT FROM AUTHOR]