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.

3-(Phenethylamino)demethyl(oxy)aaptamine as an anti-dormant mycobacterial substance: Isolation, evaluation and total synthesis.

3-(Phenethylamino)demethyl(oxy)aaptamine () was re-discovered from the marine sponge of sp. as an anti-dormant mycobacterial substance through the bioassay-guided separation. Compound showed potent anti-microbial activity against BCG with a minimum inhibitory concentration of 0.

Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain.

Detailed spatial information of low-molecular weight compound distribution, especially in the brain, is crucial to understanding their mechanism of actions. Imaging techniques that can directly visualize drugs in the brain at a high resolution will complement existing tools for drug distribution analysis. Here, we performed surface-enhanced Raman scattering (SERS) imaging using a bioorthogonal alkyne tag to visualize drugs directly in situ at a high resolution.

Secalonic acid D as a selective cytotoxic substance on the cancer cells adapted to nutrient starvation.

Cancer cells adapted to the microenvironment in tumor such as hypoxic and nutrient-starved conditions are now paid much attention as the therapeutic target of cancer. In the course of search for selective cytotoxic substances against cancer cells adapted to nutrient starvation, xanthone derivative of secalonic acid D (1) was isolated from culture extract of marine-derived Penicillium oxalicum. Compound 1 showed cytotoxic activity on the human pancreatic carcinoma PANC-1 cells adapted to glucose-starved conditions with IC value of 0.

Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation.

The core of solid tumors is characterized by hypoxia and a nutrient-starved microenvironment and has gained much attention as targets of anti-cancer drugs. In the course of search for selective growth inhibitors against the cancer cells adapted to nutrient starvation, epidithiodiketopiperazine DC1149B (1) together with structurally related compounds, trichodermamide A (2) and aspergillazine A (3), were isolated from culture extract of marine-derived Trichoderma lixii. Compounds 1 exhibited potent selective cytotoxic activity against human pancreatic carcinoma PANC-1 cells cultured under glucose-starved conditions with IC values of 0.