Violaceoid F induces nuclear translocation of FOXO3a by inhibiting CRM1 via a novel mechanism and suppresses HeLa cell growth.

FOXO3a is a transcription factor involved in cell growth inhibition and apoptosis. FOXO3a is localized in the cytoplasm in cancer cells, and its nuclear translocation by small molecules is expected to prevent cancer cell growth. In this study, we screened a fungal broth library in HeLa cells using fluorescently labeled FOXO3a and an AI-based imaging system.

Total synthesis, stereochemical assignment, and biological evaluation of opantimycin A and analogues thereof.

Opantimycin A, a rare antimycin-class antibiotic without the macrolide core, was isolated from sp. RK88-1355 in 2017. In this study, we explored the total synthesis and stereochemical assignment of opantimycin A.

Iron-sulphur protein catalysed [4+2] cycloadditions in natural product biosynthesis.

To the best of our knowledge, enzymes that catalyse intramolecular Diels-Alder ([4+2] cycloaddition) reactions are frequently reported in natural product biosynthesis; however, no native enzymes utilising Lewis acid catalysis have been reported. Verticilactam is a representative member of polycyclic macrolactams, presumably produced by spontaneous cycloaddition. We report that the intramolecular [4+2] cycloadditions can be significantly accelerated by ferredoxins (Fds), a class of small iron-sulphur (Fe-S) proteins.

Production of Kinanthraquinone D with Antimalarial Activity by Heterologous Gene Expression and Biotransformation in TK23.

Two new compounds, kinanthraquinone C () and kinanthraquinone D (), were isolated along with two known compounds, kinanthraquinone () and kinanthraquinone B (), produced by the heterologous expression of the biosynthetic gene cluster and its pathway-specific regulator, , in TK23. The chemical structures of compounds and were determined using mass spectrometry and nuclear magnetic resonance analyses. To examine a biosynthetic pathway of compounds and , incubation experiments were conducted using TK23 to supply the compounds and .

Rationalizing the Influence of the Binding Affinity on the Activity of Phosphoserine Phosphatases.

The Sabatier principle states that catalytic activity can be maximized when the substrate binding affinity is neither too strong nor too weak. Recent studies have shown that the activity of several hydrolases is maximized at intermediate values of the binding affinity (Michaelis-Menten constant: K ). However, it remains unclear whether this concept of artificial catalysis is applicable to enzymes in general, especially for those which have evolved under different reaction environments.

Total Synthesis of Clostrienose.

This paper considers the total synthesis of a cellular differentiation regulator of , clostrienose, which is a unique fatty-acid glycosyl ester consisting of clostrienoic acid, (3,5,8,10)-3-hydroxy-tetradeca-5,8,10-trienoic acid and α-d-galactofuranosyl-(1 → 2)-α-l-rhamnose. The key features of our synthesis include stereoselective construction of a skipped-triene system in clostrienoic acid and its esterification with a disaccharide residue. The partially protected clostrienoic acid employed for the coupling also served for the preparation of l-rhamnosyl clostrienoate, thus leading to confirmation of the proposed structure unambiguously.

Identification of a dihydroorotate dehydrogenase inhibitor that inhibits cancer cell growth by proteomic profiling.

Dihydroorotate dehydrogenase (DHODH) is a central enzyme of the pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases. This study presents the identification of a potent DHODH inhibitor by proteomic profiling. Cell-based screening revealed that NPD723, which is reduced to H-006 in cells, strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.

Identification of a New Pyrrolyl Pyridoindole Alkaloid, Melpyrrole, and Flazin from Honey and Their Cough-Suppressing Effect in Guinea Pigs.

The cough-suppressing effect of honey was demonstrated for the first time using a guinea pig model whereby cough was induced by citric acid and capsaicin, and a new pyrrolyl pyridoindole, 1-(5-(hydroxymethyl)-1-pyrrol-2-yl)-9-pyrido[3,4-]indole-3-carboxylic acid (), named melpyrrole, and flazin () were identified as the active principle components. The structures of and were estimated using a combination approach of an activity-guided survey and LC-MS/MS multivariate analysis and were finally established by total synthesis of and comparison with an authentic standard for . Both compounds showed antitussive activity comparable to that of dextromethorphan in guinea pigs.

cis-Decalin-containing tetramic acids as inhibitors of insect steroidogenic glutathione S-transferase Noppera-bo.

Decalin-containing tetramic acid is a bioactive scaffold primarily produced by filamentous fungi. The structural diversity of this group of compounds is generated by characteristic enzymes of fungal biosynthetic pathways, including polyketide synthase/nonribosomal peptide synthetase hybrid enzymes and decalin synthase, which are responsible for the construction of a linear polyenoyl tetramic acid structure and stereoselective decalin formation via the intramolecular Diels-Alder reaction, respectively. Compounds that differed only in the decalin configuration were collected from genetically engineered mutants derived from decalin-containing tetramic acid-producing fungi and used for a structure-activity relationship study.

Fungal NRPS-PKS Hybrid Enzymes Biosynthesize New γ-Lactam Compounds, Taslactams A-D, Analogous to Actinomycete Proteasome Inhibitors.

Proteasome inhibitors with γ-lactam structure, such as lactacystin and salinosporamide A, have been isolated from actinomycetes and have attracted attention as lead compounds for anticancer drugs. Previously, we identified a unique enzyme TAS1, which is the first reported fungal NRPS-PKS hybrid enzyme, from the filamentous fungus for the biosynthesis of a mycotoxin tenuazonic acid, a tetramic acid compound without γ-lactam structure. Homologues of have been identified in several fungal genomes and classified into four groups (A-D).

Potential Anti-Cholinesterase Activity of Bioactive Compounds Extracted from L.f. and DC.

Acetylcholinesterase (AChE) inhibitors remain the primary therapeutic drug that can alleviate Alzheimer's disease's (AD) symptoms. Several species have been shown to exert significant anti-AChE activity, which can be an alternative remedy for AD. and are potential plants with anti-AChE activity, but their phytochemical investigation is yet to be further conducted.

Naturally Occurring 8ß,13ß-kaur-15-en-17-al and Anti-Malarial Activity from Leaves.

Despite much interest and studies toward the genus , the anti-malarial evaluation of 's phytoconstituents remains lacking. Herein, the phytoconstituents of leaves and their anti-malarial effect against were investigated for the first time. One new natural product, 8ß,13ß-kaur-15-en-17-al (), along with three known compounds, 8ß,13ß-kaur-15-en-17-ol () and 13ß-kaur-16-ene (), and α-tocopherol hydroquinone () were isolated via HR-ESI-MS and NMR analyses.

Roles of in Anti-Cholinesterase, Anti-Diabetic, Anti-Inflammatory, and Antioxidant: From Alzheimer's Perspective.

Alzheimer's disease (AD) causes progressive memory loss and cognitive dysfunction. It is triggered by multifaceted burdens such as cholinergic toxicity, insulin resistance, neuroinflammation, and oxidative stress. plants are ethnomedicinally used in treating inflammation, diabetes, as well as memory impairment.

In Vitro and In Silico Anti-Acetylcholinesterase Activity from and .

(MT) and (SJ) are pharmacologically reported to have anti-oxidant, anti-inflammatory, and anti-diabetic effects, and can be neuroprotective agents. Our previous work revealed that MT and SJ exhibited 76.32% and 93.

Isolation of new lucilactaene derivatives from P450 monooxygenase and aldehyde dehydrogenase knockout Fusarium sp. RK97-94 strains and their biological activities.

Fusarium sp. RK97-94 is a producer of potent antimalarial compounds such as lucilactaene and its derivatives. The biosynthetic gene cluster of lucilactaene was identified but only a knockout mutant of methyltransferase (luc1) was reported in previous papers.

RK-270D and E, Oxindole Derivatives from sp. with Anti-Angiogenic Activity.

A chemical investigation of a culture extract from sp. RK85-270 led to the isolation and characterization of two new oxindoles, RK-270D (1) and E (2). The structures of 1 and 2 were determined by analyzing spectroscopic and spectrometric data from 1D and 2D NMR and High-resolution electrospray ionization mass spectrometry (HRESIMS) experiments.

2-Methylthio-N7-methyl-cis-zeatin, a new antimalarial natural product isolated from a Streptomyces culture.

2-Methylthio-N7-methyl-cis-zeatin (1) was isolated from the culture broth of Streptomyces sp. 80H647 along with 2 known purine derivatives, 5'-methylthioinosine (2) and AT-265 (dealanylascamycin, 3). The structure elucidation of compound 1 was accomplished by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analyses.

Thiolactomide: A New Homocysteine Thiolactone Derivative from sp. with Neuroprotective Activity.

A new homocysteine thiolactone derivative, thiolactomide (1), was isolated along with a known compound, -acetyl homocysteine thiolactone (2), from a culture extract of soil-derived sp. RK88-1441. The structures of these compounds were elucidated by detailed NMR and MS spectroscopic analyses with literature study.

Identification of a Small-Molecule Glucose Transporter Inhibitor, Glutipyran, That Inhibits Cancer Cell Growth.

Cancer cells reprogram their metabolism to survive and grow. Small-molecule inhibitors targeting cancer are useful for studying its metabolic pathways and functions and for developing anticancer drugs. Here, we discovered that glutipyran and its derivatives inhibit glycolytic activity and cell growth in human pancreatic cancer cells.

Zealpeptaibolin, an 11-mer cytotoxic peptaibol group with 3 Aib-Pro motifs isolated from Trichoderma sp. RK10-F026.

Six new 11-mer peptaibols designed as zealpeptaibolins, A - F were isolated from the soil fungus, Trichoderma sp. RK10-F026, based on the principal component analysis of the MS data from five different culture compositions. Previously, 20-mer peptaibols from the same fungal strain were identified; 11-mer peptaibols in contrast were discovered from a different culture condition, signifying peptaibol production was culture condition-dependent.

Molecular Basis for Two Stereoselective Diels-Alderases that Produce Decalin Skeletons*.

Enzymes catalyzing [4+2] cycloaddition have attracted increasing attention because of their key roles in natural product biosynthesis. Here, we solved the X-ray crystal structures of a pair of decalin synthases, Fsa2 and Phm7, that catalyze intramolecular [4+2] cycloadditions to form enantiomeric decalin scaffolds during biosynthesis of the HIV-1 integrase inhibitor equisetin and its stereochemical opposite, phomasetin. Computational modeling, using molecular dynamics simulations as well as quantum chemical calculations, demonstrates that the reactions proceed through synergetic conformational constraints assuring transition state-like substrates folds and their stabilization by specific protein-substrate interactions.

Antioxidant, Anti-Inflammatory, and Inhibition of Acetylcholinesterase Potentials of DC. Flowers.

Despite being widely used traditionally as a general tonic, especially in South East Asia, scientific research on , remains scarce. In this study, the aim was to evaluate the in vitro activities for acetylcholinesterase (AChE) inhibitory potential, radical scavenging ability, and the anti-inflammatory properties of different extracts of flowers using Ellman's assay, a DPPH assay, and an albumin denaturation assay, respectively. With the exception of the acetylcholinesterase activity, to the best of our knowledge, these activities were reported for the first time for flowers.

N-Acetyl-α-hydroxy-β-oxotryptamine, a racemic natural product isolated from Streptomyces sp. 80H647.

N-acetyl-α-hydroxy-β-oxotryptamine (1) along with N-acetyl-β-oxotryptamine (2) and pimprinine (3) were isolated from the culture broth of Streptomyces sp. 80H647. Compound 1 was found to be a racemate via X-ray diffraction analysis and the enantiomers were successfully purified by chiral-phase HPLC.