Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges.

Tuberculosis (TB) poses a persistent global health threat exacerbated by the emergence of drug-resistant strains; hence, there is a continuous quest for novel antimicrobial agents. Despite efforts to develop effective therapies, existing treatments require a relatively long duration of therapy to eradicate the pathogen due to its virulence factors, pathogenesis patterns, and ability to enter dormant states. This can lead to a higher risk of treatment failure due to poor patient adherence to the complex regimen.

Oleanane-type triterpene saponins promote extracellular vesicle secretion of human adipose-derived mesenchymal stem cells.

The application of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) holds significant promise in anti-aging cosmetics, regenerative medicine, and drug delivery systems. However, their limited production efficiency remains a critical barrier to advancing related therapies and pharmaceutical applications. In this study, a library of triterpene saponins was screened, leading to the re-discovery of an oleanane-type triterpene saponin Lucyoside H (1), along with its structural analogs, Chikusetsusaponins IVa (2), IV (3), and V (4), which were found to increase the production of EV from human adipose-derived mesenchymal stem cells (ADMSCs) at a concentration ranging from 10 to 100 µM.

Synthesis and Evaluation of Antitumor and Anti-Angiogenesis Activity of Pyrone- or Pyridone-Embedded Analogs of Cortistatin A.

Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyrone- or pyridone-embedded analogs were designed and synthesized. Among the prepared analogs, the pyridone analog bearing a methyl group at C-2 and a hydroxyl group at C-4 showed potent and selective growth inhibitory activity against human umbilical vein endothelial cells (HUVECs, IC = 0.

Effective Repeated Production of γ-glutamylcysteine, Essential For Intracellular Glutathione Production, Using Cellulose-immobilized Phytochelatin Synthase-like Enzyme NsPCS.

γ-Glutamylcysteine (γ-EC) can increase intracellular glutathione (GSH) levels, which may prevent and alleviate age-related disorders and chronic diseases caused by oxidative damage. However, the commercial availability of γ-EC remains limited owing to its complex chemical synthesis from glutamate and cysteine. In this study, we have developed the method of the effective conversion of GSH to γ-EC to achieve the optimal reaction conditions for repeated batch production and potential application in industrial γ-EC production using the phytochelatin synthase-like enzyme NsPCS.

An Investigation into the Phytochemical Content and Antioxidant, Antidiabetic, and Wound-Healing Activities of Found in Brunei Darussalam.

This present study aimed to investigate the phytochemical content and antioxidant and antidiabetic activities of leaves (CL) and roots (CR) found in Brunei Darussalam. Phytochemical screening showed that CL and CR extracts contain saponins, tannins, glycosides, and terpenoids. CR showed higher total phenolic content (TPC), but lower total flavonoid content (TFC) when compared to CL.

Chemical Constituents and Anticancer Activities of Marine-Derived Fungus .

The fungal genus is a rich source of structurally diverse secondary metabolites with remarkable pharmaceutical properties. The chemical constituents and anticancer activities of the marine-derived fungus have never been investigated. In this study, a bioactivity-guided investigation led to the isolation of eleven compounds, including trichodermamide A (), trichodermamide B (), aspergillazine A (), DC1149B (), ergosterol peroxide (), cerebrosides D/C (), 5-hydroxy-2,3-dimethyl-7-methoxychromone (), nafuredin A (), and harzianumols E/F (/).

Proposal for structure revision of pinofuranoxin A through total syntheses of stereoisomers.

The relative configuration of the epoxide functionality in pinofuranoxin A (1), α-alkylidene-β-hydroxy-γ-methyl-γ-butyrolactone with trans-epoxy side chain isolated by Evidente et al. in 2021, was revised by DFT-based spectral reinvestigations and stereo-controlled synthesis. The present investigation demonstrates the difficulty of the configurational elucidation of the stereogenic centers on the conformationally flexible acyclic side-chains.

First Total Syntheses of Beauvericin A and -Beauvericin A.

The first total syntheses of beauvericin A and -beauvericin A were achieved. -Methyl-l-phenylalanine, (2)-hydroxylvaleric acid, and (2,3)- or (2,3)-2-hydroxy-2-methylpentanoic acid were linked and cyclized to form the target natural products. The structure of synthetic beauvericin A was confirmed by X-ray crystallographic analysis.

Impact of multiple H/D replacements on the physicochemical properties of flurbiprofen.

Although deuterium incorporation into pharmaceutical drugs is an attractive way to expand drug modalities, their physicochemical properties have not been sufficiently examined. This study focuses on examining the changes in physicochemical properties between flurbiprofen (FP) and flurbiprofen- (FP-), which was successfully prepared by direct and multiple H/D exchange reactions at the eight aromatic C-H bonds of FP. Although the effect of deuterium incorporation was not observed between the crystal structures of FP and FP-, the melting point and heat of fusion of FP- were lower than those of FP.

Cytotoxic activity of cordycepin produced by marine-derived fungus Emericella sp. against HT29 human colon cancer cell lines.

Colorectal cancer accounted for the third most common cancer in the world. The search for new drug candidates that can be used for colorectal cancer treatment from marine-derived fungi, Emericella sp. The present study was performed to isolate the cytotoxic compound from Emericella sp.

A New Tetracyclic Bromopyrrole-Imidazole Derivative through Direct Chemical Diversification of Substances Present in Natural Product Extract from Marine Sponge () sp.

Chemical diversification of substances present in natural product extracts can lead to a number of natural product-like compounds with a better chance of desirable bioactivities. The aim of this work was to discover unprecedented chemical conversion and produce new compounds through a one-step reaction of substances present in the extracts of marine sponges. In this report, a new unnatural tetracyclic bromopyrrole-imidazole derivative, -6-Et-cylindradine A (), was created from a chemically diversified extract of the sponge sp.

Anti-Mycobacterial -(2-Arylethyl)quinolin-3-amines Inspired by Marine Sponge-Derived Alkaloid.

The synthesis and evaluation of simplified analogs of marine sponge-derived alkaloid 3-(phenethylamino)demethyl(oxy)aaptamine were performed to develop novel anti-mycobacterial substances. Ring truncation of the tricyclic benzo[][1,6]-naphthyridine skeleton effectively weakened the cytotoxicity of the natural product, and the resulting AC-ring analog exhibited good anti-mycobacterial activity. A structure-activity relationship (SAR) study, synthesizing and evaluating some analogs, demonstrated the specificity and importance of the -(2-arylethyl)quinolin-3-amine skeleton as a promising scaffold for anti-mycobacterial lead compounds.

Design, Synthesis, and Monoamine Oxidase B Selective Inhibitory Activity of -Arylated Heliamine Analogues.

Monoamine oxidase B (MAO-B) metabolizes monoamines such as dopamine regarding neural transmission and controls its level in the mammalian's brain. When MAO-B metabolizes dopamine abnormally, normal neurotransmission does not occur, and central nervous system disorders such as Parkinson's disease may develop. Although several MAO inhibitors have been developed, most of them have no selectivity between monoamine oxidase A (MAO-A) and MAO-B, or they work irreversibly against the enzyme.

Gamma-Glutamylcysteine Production Using Phytochelatin Synthase-Like Enzyme Derived from Nostoc sp. Covalently Immobilized on a Cellulose Carrier.

Gamma-glutamylcysteine (γ-EC) is an intermediate generated in the de novo synthesis of glutathione (GSH). Recent studies have revealed that the administration of γ-EC shows neuroprotective effects against oxidative stress in age-related disorders and chronic diseases like Alzhiemer's disease in model animals, which is not expected function in GSH. A phytochelatin synthase-like enzyme derived from Nostoc sp.

Single-step construction of an acetoxypyrroloindole skeleton tandem iodocyclization/acetoxylation of indoles.

A method for the synthesis of C3a acetoxy hexahydropyrrolo[2,3-]indole derivatives a PhI(OAc)/BuNI mediated tandem iodocyclization/acetoxylation has been developed. The newly developed synthetic strategy features the single-step assembly of various C3a acetoxylated tetrahydropyrrole-, tetrahydrofuran-, and lactone-fused indolines under mild reaction conditions, which enabled efficient asymmetric synthesis of (-)-protubonine B.

Oridonin suppresses particulate-induced NLRP3-independent IL-1α release to prevent crystallopathy in the lung.

The human body is exposed to various particulates of industrial, environmental, or endogenous origin. Invading or intrinsic particulates can induce inflammation by aberrantly activating the immune system, thereby causing crystallopathies. When immune cells such as macrophages phagocytose the particulates, their phagolysosomal membranes undergo mechanical damage, eventually leading to pyroptotic cell death accompanied by the release of inflammatory cytokines, including interleukin (IL)-1α and IL-1β.

Asteltoxin inhibits extracellular vesicle production through AMPK/mTOR-mediated activation of lysosome function.

Cancer cells secrete aberrantly large amounts of extracellular vesicles (EVs) including exosomes, which originate from multivesicular bodies (MVBs). Because EVs potentially contribute to tumor progression, EV inhibitors are of interest as novel therapeutics. We screened a fungal natural product library.

Fungicide Activity of Culture Extract from 19C38A1 against .

Secondary metabolites of actinomycetes are a potential source of bioactive compounds in the agricultural sector. This study aimed to determine the fungicidal properties of extracts of marine organism-derived actinomycetes. Actinomycetes were isolated from marine organisms using agar media with 1% colloidal chitin in artificial seawater.

Study of the Structure-Activity Relationship of an Anti-Dormant Mycobacterial Substance 3-(Phenethylamino)Demethyl(oxy)aaptamine to Create a Probe Molecule for Detecting Its Target Protein.

The current tuberculosis treatment regimen is long and complex, and its failure leads to relapse and emergence of drug resistance. One of the major reasons underlying the extended chemotherapeutic regimen is the ability of to attain a dormant state. Therefore, the identification of new lead compounds with chemical structures different from those of conventional anti-tuberculosis drugs is essential.

Synthesis and biological evaluation of cajaninstilbene acid and amorfrutins A-D as cytotoxic agents against human pancreatic carcinoma PANC-1 cells.

A concise synthesis of cajaninstilbene acid was achieved in 7 steps from (E)-3,5-dimethoxystilbene in 8.6% overall yield via the Claisen rearrangement of an aryl reverse-prenyl ether as the key step. Cytotoxic activities against human pancreatic carcinoma PANC-1 cells of cajaninstilbene acid and amorfrutins A-D were also evaluated.

Reactivity of γ-glutamyl-cysteine with intracellular and extracellular glutathione metabolic enzymes.

Gamma-glutamyl-cysteine (γ-EC) is a precursor of glutathione (GSH) biosynthesis. We investigated whether it functions as a substrate for three intracellular and one extracellular GSH metabolic enzymes, which mediate the antioxidant defence function of GSH. Among them, glutathione peroxidase, glutathione S-transferase and γ-glutamyl transferase (GGT) exhibited substrate specificity for γ-EC, whereas glutathione reductase did not.

Mitochondrial Targeting in an Anti-Austerity Approach Involving Bioactive Metabolites Isolated from the Marine-Derived Fungus sp.

The tumor microenvironment is a nutrient-deficient region that alters the cancer cell phenotype to aggravate cancer pathology. The ability of cancer cells to tolerate nutrient starvation is referred to as austerity. Compounds that preferentially target cancer cells growing under nutrient-deficient conditions are being employed in anti-austerity approaches in anticancer drug discovery.

Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation.

The cancer cells that are adapted to the hypoxic and nutrient-starved conditions of the tumor microenvironment have become a key target for anticancer therapies. In the course of search for selective cytotoxic substances against cancer cells adapted to nutrient starvation, (3S,6S)-3,6-dibenzylpiperazine-2,5-dione (1) was isolated from culture extract of marine-derived Paecilomyces formous 17D47-2. Compound 1 showed cytotoxic activity on the human pancreatic carcinoma PANC-1 cells adapted to glucose-starved conditions with IC value of 28 µM, whereas no effect was observed against PANC-1 cells under general culture conditions up to 1000 µM.