Cheminformatics-Guided Exploration of Synthetic Marine Natural Product-Inspired Brominated Indole-3-Glyoxylamides and Their Potentials for Drug Discovery.

Marine natural products (MNPs) continue to be tested primarily in cellular toxicity assays, both mammalian and microbial, despite most being inactive at concentrations relevant to drug discovery. These MNPs become missed opportunities and represent a wasteful use of precious bioresources. The use of cheminformatics aligned with published bioactivity data can provide insights to direct the choice of bioassays for the evaluation of new MNPs.

Synthesis and Cheminformatics-Directed Antibacterial Evaluation of Echinosulfonic Acid-Inspired Bis-Indole Alkaloids.

Synthetic efforts toward complex natural product (NP) scaffolds are useful ones, particularly those aimed at expanding their bioactive chemical space. Here, we utilised an orthogonal cheminformatics-based approach to predict the potential biological activities for a series of synthetic bis-indole alkaloids inspired by elusive sponge-derived NPs, echinosulfone A () and echinosulfonic acids A-D (-). Our work includes the first synthesis of desulfato-echinosulfonic acid C, an α-hydroxy bis(3'-indolyl) alkaloid (), and its full NMR characterisation.

Structure Revision of Formyl Phloroglucinol Meroterpenoids: A Unified Approach Using NMR Fingerprinting and DFT NMR and ECD Analyses.

NMR fingerprints are valuable tools for analyzing complex natural product mixtures and identifying incorrectly assigned structures in the literature. Our diagnostic NMR fingerprints for formyl phloroglucinol meroterpenoids revealed discrepancies in the structures reported for eucalyprobusal C () and eucalypcamal K (). NMR fingerprinting PCA analyses identified as an oxepine-diformyl phloroglucinol and as an oxepine 3-acyl-1-formyl phloroglucinol, contrary to their initial assignments as pyrano-diformyl and pyrano 3-acyl-1-formyl phloroglucinols, respectively.

Marine natural products.

Covering: January to the end of December 2022This review covers the literature published in 2022 for marine natural products (MNPs), with 645 citations (633 for the period January to December 2022) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, the submerged parts of mangroves and other intertidal plants. The emphasis is on new compounds (1417 in 384 papers for 2022), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included.

α-Synuclein Aggregation Inhibitory and Antiplasmodial Activity of Constituents from the Australian Tree .

Amyloid protein aggregates are linked to the progression of neurodegenerative conditions and may play a role in life stages of , the parasite responsible for malaria. We hypothesize that amyloid protein aggregation inhibitors may show antiplasmodial activity and vice versa. To test this hypothesis, we screened antiplasmodial active extracts from 25 Australian eucalypt flowers using a binding affinity mass spectrometry assay to identify molecules that bind to the Parkinson's disease-implicated protein α-syn.

Cyclotheonellazoles D-I, Potent Elastase Inhibitory Thiazole-Containing Cyclic Peptides from sp. (2131).

Six new thiazole-containing cyclic peptides, the cyclotheonellazoles D-I (-), were isolated from the Australian marine sponge sp. (2131) with their structures assigned by comprehensive 1D and 2D NMR spectroscopic and MS spectrometric analyses, Marfey's derivatization studies, and comparison with time-dependent density functional theory (TDDFT) calculated ECD data. The Type 2 azole-homologated peptides herein comprise up to five nonproteinogenic amino acids, including the protease transition state mimic α-keto-β-amino acid residue 3-amino-4-methyl-2-oxohexanoic acid (Amoha), while - also contain a terminal hydantoin residue not previously found in cyclotheonellazoles.

Camaldulensals A-C, the First Meroterpenoids Possessing Two Spatially Separated Formyl Phloroglucinols Conjugated to a Terpene Core from the Leaves of Dehnh.

Three new bis-formyl phloroglucinol-meroterpenoids (-), three new euglobal type formyl phloroglucinol-meroterpenoids (-), and one new dimeric formyl phloroglucinol () were isolated from the leaves of . Camaldulensal A () is the first bis-isovaleryl-formyl-phloroglucinol-sesquiterpenoid. It features a novel 6/6/10/3/6/6 fused ring system and contains six stereogenic centers.

Letter to the editor on "Antimicrobial compounds isolated from .

A bisphosphonate recently isolated from Tropaeolum tuberosum is almost certainly a contaminant and not a genuine natural product.

NMR Fingerprints of Formyl Phloroglucinol Meroterpenoids and Their Application to the Investigation of subsp. .

NMR fingerprints provide powerful tools to identify natural products in complex mixtures. Principal component analysis and machine learning using H and C NMR data, alongside structural information from 180 published formyl phloroglucinols, have generated diagnostic NMR fingerprints to categorize subclasses within this group. This resulted in the reassignment of 167 NMR chemical shifts ascribed to 44 compounds.

The combined effects of manual therapy and exercise on pain and related disability for individuals with nonspecific neck pain: A systematic review with meta-analysis.

Background: Neck pain is among the most prevalent and costly musculoskeletal disorders. Manual therapy and exercise are two standard treatment approaches to manage neck pain. In addition, clinical practice guidelines recommend a multi-modal approach, including both manual therapy and exercise for the treatment of neck pain; however, the specific effects of these combined interventions have not recently been reported in the literature.

Amphiphilic Polyamine α-Synuclein Aggregation Inhibitors from the Sponge .

Bioassay-guided investigation of the sponge resulted in the isolation and identification of two new amphiphilic polyamines, aaptolobamines A () and B (). Their structures were determined through analysis of NMR and MS data. MS analysis also indicated that contained a complex mixture of aaptolobamine homologues.

Marine indole alkaloid diversity and bioactivity. What do we know and what are we missing?

Covering: marine indole alkaloids ( = 2048) and their reported bioactivities up to the end of 2021Despite 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.

α-Synuclein Aggregation Inhibitory Procerolides and Diphenylalkanes from the Ascidian .

The aggregation of the neuronal protein α-synuclein (α-syn) is intrinsically linked to the development and progression of Parkinson's disease (PD). Recently we screened the MeOH extracts from 283 marine invertebrates for α-syn binding activity using an affinity mass spectrometry (MS) binding assay and found that the extract of the ascidian displayed activity. A subsequent bioassay-guided purification led to the isolation of one new α-syn aggregation inhibitory butenolide procerolide E () and one new α-syn aggregation inhibitory diphenylbutyrate methyl procerolate A ().

Marine natural products.

Covering: January to December 2021This review covers the literature published in 2021 for marine natural products (MNPs), with 736 citations (724 for the period January to December 2021) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1425 in 416 papers for 2021), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included.

Field-scale monitoring of green sea turtles (Chelonia mydas): Influence of site characteristics and capture technique on the blood metabolome.

Given their threatened status, there is considerable interest in establishing monitoring techniques that can be used to evaluate the health of sea turtles in the wild. The present study represents a methodological contribution towards field-scale metabolomic assessment of sea turtles, by exploring differences in blood biochemistry associated with site characteristics and capture technique. We compared the metabolome of blood from animals at three locations (two coastal and one reefal), collected from turtles that were either resting or active, and sampled across multiple seasons at one location.

Understanding of black salve toxicity by multi-compound cytotoxicity assays.

Background: Black salve is a controversial complementary and alternative medicine (CAM) associated with skin toxicity and skin cancer treatment failures. Black salve formulations vary between manufacturers and contain a number of botanical and synthetic constituents. The skin cancer cytotoxicity of a number of these constituents has not been assessed to date.

Echiumin E, an Aryl Dihydronaphthalene Lignan from the Australian Invasive Plant Paterson's Curse ().

A new aryl dihydronaphthalene lignan, echiumin E (), and four known compounds, echiumin A, globoidnan A, (-)-rabdosiin, and rosmarinic acid (-), were isolated from the Australian invasive plant (Paterson's curse) for the first time. Echiumin E () was characterized by 1D/2D NMR spectroscopy and MS spectrometry, with its absolute configuration assigned through comparison of experimental and TDDFT-calculated ECD data. Echiumin E () along with compounds - were screened in vitro against three cancer cell lines (SH-SY5Y, HeLa, and PC-3) and a prostate stromal (normal) cell line (WPMY-1) using a resazurin reduction assay.

Exploring lipid affinities of persistent organic pollutants and MeO-PBDEs in blubber of marine mammals.

Although lipophilic compounds have been the focus of numerous studies in marine mammals, their association with lipids is widely accepted, but rarely scrutinized. This pilot study aimed to investigate potential relationships between individual lipids from different lipid classes identified through a non-targeted Nuclear Magnetic Resonance (NMR) based lipidomics approach and legacy POPs in the blubber of long-finned pilot whales, sperm whales, common bottlenose dolphins, and Indo-Pacific bottlenose dolphins. Concentrations of selected POPs such as HCB and HCHs in sperm whales from Tasmania were found to differ from those in long-finned pilot whales and common bottlenose dolphins from the same location.

α-Synuclein binding activity of the plant growth promoter asterubine.

Preventing the aggregation of certain amyloid proteins has the potential to slow down the progression of diseases like Alzheimer's, Parkinson's, and type 2 diabetes mellitus. During a high-throughput screen of 300 Australian marine invertebrate extracts, the extract of the marine sponge Thorectandra sp. 4408 displayed binding activity to the Parkinson's disease-associated protein, α-synuclein.

Marine natural products.

Covering: 2020This review covers the literature published in 2020 for marine natural products (MNPs), with 757 citations (747 for the period January to December 2020) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1407 in 420 papers for 2020), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included.

α-Synuclein Aggregation Inhibitory Prunolides and a Dibrominated β-Carboline Sulfamate from the Ascidian .

Seven new polyaromatic bis-spiroketal-containing butenolides, the prunolides D-I (-) and -prunolide C (), a new dibrominated β-carboline sulfamate named pityriacitrin C (), alongside the known prunolides A-C (-) were isolated from the Australian colonial ascidian . The prunolides D-G (-) represent the first asymmetrically brominated prunolides, while -prunolide C () is the first reported with a -configuration about the prunolide's bis-spiroketal core. The prunolides displayed binding activities with the Parkinson's disease-implicated amyloid protein α-synuclein in a mass spectrometry binding assay, while the prunolides (- and ) were found to significantly inhibit the aggregation (>89.

Sycosterol A, an α-Synuclein Inhibitory Sterol from the Australian Ascidian .

During a recent biodiscovery study to identify new α-synuclein (α-syn) aggregation inhibitors, we screened 29 Australian marine sponge and ascidian extracts in an MS binding assay. This resulted in an extract from the ascidian showing activity toward α-syn. The bioassay and MS guided isolation process led to the identification of one new polyoxygenated sterol sulfate, sycosterol A ().

How different are marine microbial natural products compared to their terrestrial counterparts?

Covering: 1877 to 2020A key challenge in natural products research is the selection of biodiversity to yield novel chemistry. Recently, marine microorganisms have become a preferred source. But how novel are marine microorganism natural products compared to those reported from terrestrial microbes? Cluster analysis of chemical fingerprints and molecular scaffold analysis of 55 817 compounds reported from marine and terrestrial microorganisms, and marine macro-organisms showed that 76.

Natural products dereplication by diffusion ordered NMR spectroscopy (DOSY).

Diffusion-ordered NMR spectroscopy (DOSY) can be used to analyze mixtures of compounds since resonances deriving from different compounds are distinguished by their diffusion coefficients (). Previously, DOSY has mostly been used for organometallic and polymer analysis, we have now applied DOSY to investigate diffusion coefficients of structurally diverse organic compounds such as natural products (NP). The experimental s derived from 55 diverse NPs has allowed us to establish a power law relationship between and molecular weight (MW) and therefore predict MW from experimental .

Terrestrial dissolved organic matter source affects disinfection by-product formation during water treatment and subsequent toxicity.

Restoring woody vegetation to riparian zones helps to protect waterways from excessive sediment and nutrient inputs. However, the associated leaf litter can be a major source of dissolved organic matter (DOM) leached into surface waters. DOM can lead to the formation of disinfection by-products (DBPs) during drinking water treatment.