Antiplasmodial activity of tambjamines, dihydro-β-agarofurans and pyrroloazepines derived from Australian plant and marine species.

Malaria is a significant cause of morbidity and mortality, with 263 million cases and 597,000 deaths estimated in 2023. While effective drug combinations are available to prevent and treat malaria, Plasmodium parasite drug resistance is compromising all current options. This situation means that new drugs that act on novel Plasmodium drug targets are needed.

Genome Mining-Based Discovery of Pyrano[2,3-]pyrrole Type Natural Products Possessing Alkyl Side Chain with Branched Methyl Groups.

Genome mining of polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) in fungal endophyte strain BRIP 39872 identified seven new natural products (olumilides A-D, D1, D1', D2) with pyrano[2,3-]pyrrole scaffolds and their biosynthetic precursor preolumilide. Unlike known congeners, such as curvupallides, olumilides possess alkyl side chains with branched methyl groups and threonine-derived core scaffolds. Absolute configurations were determined by microED and ECD simulations, providing valuable information for further research focusing on the stereochemistry of PKS-NRPS reactions.

Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge .

A recent high-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract from the Australian marine sponge with in vitro activity against an economically important parasitic nematode, (barber's pole worm). The bioassay-guided fractionation of the CHCl/MeOH extract from led to the purification of a new diterpene alkaloid, agelasine Z (), together with two known compounds agelasine B () and oxoagelasine B (). Brominated compounds (-)-mukanadin C () and 4-bromopyrrole-2-carboxylic acid () were also isolated from neighbouring UV-active fractions.

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-]pyrazine scaffold.

1,2,4-Triazolo[4,3-]pyrazines have previously been explored by the Open Source Malaria project as potent in vitro and in vivo antimalarial drug leads. With a view to generating a library of unique antimalarial 1,2,4-triazolo[4,3-]pyrazines and exploring regiochemical preference for nucleophilic amines, we utilised the known synthetic 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-]pyrazine () as a scaffold for aminations with 14 commercially available primary amines. Reacting scaffold with excess primary amine at room temperature for 16 h generated the desired amine analogues in respectable yields (18-87%) and high purity (≥95%) following chromatography workup.

Transcriptomic Plasticity of Human Alveolar Macrophages Revealed by Single-Cell RNA Sequencing Following Drug Exposure: Implications for Therapeutic Development.

Alveolar macrophages (AM) must perform three seemingly opposing roles including homeostasis, driving inflammation, and facilitating tissue repair. Whilst there is now consensus (supported by a large body of human single cell RNA sequencing (scRNA-seq) data) that the cell subsets that perform these tasks can readily be found based on their transcriptome, their ontogeny has remained unclear. Moreover, there is agreement that in all types of pulmonary fibrosis (PF) there is an expanded population of profibrotic AM that may aberrantly drive PF.

Discovery of ianthelliformisamines D-G from the sponge and the total synthesis of ianthelliformisamine D.

The marine sponge was investigated for new chemistry after the recent discovery that polyamines ianthelliformisamines A-C (-) - originally sourced from this Australian sponge - act as biofilm inhibitors and antibiotic enhancers. Large-scale extraction and isolation studies resulted in the discovery of four new and minor natural products, ianthelliformisamines D-G (-) and the known steroid, aplysterol (). Compounds - were fully characterised following 1D/2D NMR, MS and UV data analyses.

Inhibition of Human Salivary and Pancreatic α-Amylase by Resveratrol Oligomers.

A key strategy to mitigate postprandial hyperglycemia involves inhibiting α-amylases, which commence the starch digestion process in the gut. This study examined the inhibitory effects of resveratrol and stilbenoid tetramers, vaticanol B, (-)-hopeaphenol, and vatalbinoside A on human salivary and pancreatic α-amylases experimentally and through molecular docking studies. Vaticanol B demonstrated the most potent inhibition with IC values of 5.

Identification of Axinellamines A and B as Anti-Tubercular Agents.

Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and to offer effective and additive therapeutic options. High-throughput screening of a subset of the NatureBank marine fraction library ( = 2000) identified a sample derived from an Australian marine sponge belonging to the order Haplosclerida that displayed promising anti-mycobacterial activity.

Chemical and Antiplasmodial Investigations on -Derived Alkaloids and Semisynthetic Ether Analogues.

Microthecaline A (), the known antiplasmodial quinoline serrulatane alkaloid from the roots of F. Muell. ex Benth.

Semisynthesis and Cytotoxic Evaluation of an Ether Analogue Library Based on a Polyhalogenated Diphenyl Ether Scaffold Isolated from a Sponge.

The known oxygenated polyhalogenated diphenyl ether, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol (), with previously reported activity in multiple cytotoxicity assays was isolated from the sponge sp. and proved to be an amenable scaffold for semisynthetic library generation. The phenol group of was targeted to generate 12 ether analogues in low-to-excellent yields, and the new library was fully characterized by NMR, UV, and MS analyses.

Bromotyrosine-Derived Metabolites from a Marine Sponge Inhibit Biofilms.

forms stable biofilms, providing a major barrier for multiple classes of antibiotics and severely impairing treatment of infected patients. The biofilm matrix of this Gram-negative bacterium is primarily composed of three major exopolysaccharides: alginate, Psl, and Pel. Here, we studied the antibiofilm properties of sponge-derived natural products ianthelliformisamines A-C and their combinations with clinically used antibiotics.

Synthesis and Antimalarial Evaluation of Halogenated Analogues of Thiaplakortone A.

The incorporation of bromine, iodine or fluorine into the tricyclic core structure of thiaplakortone A (), a potent antimalarial marine natural product, is reported. Although yields were low, it was possible to synthesise a small nine-membered library using the previously synthesised Boc-protected thiaplakortone A () as a scaffold for late-stage functionalisation. The new thiaplakortone A analogues (-) were generated using -bromosuccinimide, -iodosuccinimide or a Diversinate™ reagent.

The Natural Stilbenoid (-)-Hopeaphenol Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9.

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (-)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production.

Using a Bioactive -Derived Serrulatane Scaffold to Generate a Unique Carbamate Library for Anti-infective Evaluations.

The known -derived diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid () was targeted for large-scale purification, as this bioactive plant compound has proven to be an attractive scaffold for semisynthetic studies and subsequent library generation. Compound was converted to a selectively protected trimethyl derivative, 3-hydroxy-7,8-dimethoxyserrulat-14-en-19-oic acid methyl ester (), using simple and rapid methylation conditions. The resulting scaffold was reacted with a diverse series of commercially available isocyanates to generate an 11-membered carbamate-based library.

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.

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds.

Nine new fluorinated analogues were synthesised by late-stage functionalisation using Diversinate™ chemistry on the Open Source Malaria (OSM) triazolopyrazine scaffold (Series 4). The structures of all analogues were fully characterised by NMR, UV and MS data analysis; three triazolopyrazines were confirmed by X-ray crystal structure analysis. The inhibitory activity of all compounds against the growth of the malaria parasite (3D7 and Dd2 strains) and the cytotoxicity against a human embryonic kidney (HEK293) cell line were tested.

Using UHPLC-MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library.

In order to further expand the NatureBank open access compound library, chemical investigations of the Australian marine sponge, were undertaken since UHPLC-MS analysis of the extract from this sponge indicated the presence of a new alkaloid. Large-scale extraction and mass-directed isolation studies on the CHCl/MeOH extract resulted in the purification of a new bromotyrosine-derived alkaloid, 5-debromopurealidin H (), along with the known marine natural product, ianthesine E (). The chemical structure of the new compound was determined following detailed spectroscopic and spectrometric data analysis.

Thiaplakortone B attenuates RANKL-induced NF-κB and MAPK signaling and dampens OVX-induced bone loss in mice.

Osteoclasts play an important role in maintaining the relative stability of bone mass. Abnormal number and function of osteoclasts are closely related to osteoporosis and osteolytic diseases. Thiaplakortone B (TPB), a natural compound derived from the Great Barrier Reef sponge Plakortis lita, has been reported to inhibit the growth of the malaria parasite, Plasmodium falciparum, but its effect on osteoclastogenesis has not been previously investigated.

Identification of Anthelmintic Bishomoscalarane Sesterterpenes from the Australian Marine Sponge and Structure Revision of Phyllolactones A-D.

High-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract derived from the Australian marine sponge with activity against (barber's pole worm), an economically important parasitic nematode. Bioassay-guided fractionation of the CHCl/MeOH extract from led to the purification of four known bishomoscalarane sesterterpenes, phyllolactones A-D (-). The absolute configurations of phyllolactones B () and C () were determined by single-crystal X-ray diffraction analysis; literature and data analyses revealed the need for these chemical structures to be revised.

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.