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Abstract: 10,11-Dehydrocurvularin is a natural benzenediol lactone (BDL) with a 12-membered macrolide fused to a resorcinol ring produced as a secondary metabolite by many fungi. In this review, we summarized the pieces of literature regarding biosynthesis, chemical synthesis, biological activities, and assumed work mechanisms of 10,11-dehydrocurvularin, which presented a potential for agricultural and pharmaceutical uses.

Protein arginine methyltransferases (PRMTs), enzymes catalyzing the methylation of target proteins, play an essential role in maintaining functional homeostasis in normal physiology. Aberrant expressions and enhanced enzymatic activities of PRMTs have been closely associated with pathological states such as cancer, inflammatory, immune, metabolic, and neurodegenerative diseases. Therefore, the development of inhibitors targeting PRMTs has attracted a great deal of attention in both pharmaceutical industries and academic community. This review focuses on the small-molecule inhibitors targeting PRMTs in cancer therapy in the patents published since 2019. The recent clinical development is also discussed here. In recent years, the discovery of small-molecule PRMT inhibitors, especially PRMT5 inhibitors has become a rapidly expanding research area for cancer therapy. Although a number of potent PRMT inhibitors with different chemical scaffolds have been developed and nine of them have entered into clinical trials, their scaffolds are relatively less diverse. Sub-type selectivity should be considered in drug discovery as nonselective inhibition of PRMTs may cause undesirable pharmacological effects. Hence, the development of new effective inhibitors with isoform-specific and tumor-biased distributions remains an important area for further studies.

An open-air palladium-catalyzed O-glycosylation was developed using glycals and arylboronic acids with base additives at ambient conditions. The novel approach enabled facile access to various

Precipitation formation commonly occurs in the ageing step of fermented citrus vinegar. Hitherto, the chemical characteristics and biological properties of precipitates remain unveiled. This study focused on investigating the chemical profile, formation mechanism and biological repurposing of precipitates. Nine principal components, two flavonoid glycosides and their aglycones along with five polymethoxyflavones (PMFs), were identified from a methanol extract of precipitates. Using hydrolysis models, we demonstrated that insoluble aglycones were generated through the breakage of glycosidic bonds in flavonoid glycosides under acidic condition. Moreover, soluble bound-PMFs were destroyed by yeast-acid hybrid catalysis to release insoluble free-PMFs to form precipitates. A methanol extract of precipitates exhibited a potent anti-proliferative effect on MCF-7 cells (IC

An exclusive asymmetric reduction of CO bonds of 2-arylidene four-, five-, six-, and seven-membered cycloalkanones has been studied systematically. The asymmetric transfer hydrogenation was performed using a robust and commercially available chiral diamine-derived ruthenium complex as a catalyst and HCOOH/Et3N as a hydrogen source under mild conditions, giving 51 examples of chiral exocyclic allylic alcohols in up to 96% yield and 99% ee. This method was also applicable to the gram-scale synthesis of the active intermediates of the anti-inflammatory loxoprofen and natural product (−)-goniomitine.

We report a quantitative chemoproteomic approach that utilizes a clickable photoreactive probe for global profiling of celastrol targets, which may significantly improve the current understanding of celastrol's mode of action.

Cancer cells rely on fatty acid synthase (FASN), a key enzyme for de novo biosynthesis of long chain fatty acids, to sustain their proliferative potential and drive invasion. Unfortunately, conventional FASN assays are technically inadequate for discerning otherwise elusive FASN activity in complex biological milieux, which has hindered progress in the functional study of FASN and development of its inhibitors. Here, we describe a chemical probe with unprecedented selectivity and sensitivity for the labeling of active FASN in living cells, thus demonstrating a new analytical modality for visualizing endogenous FASN activity and exploring opportunities for drug discovery.

Structure-guided isolation of a CH

DNAzyme-based chemiluminescence assay exhibits excellent performance in bioanalysis but their operation in acid conditions remains challengeable. Herein, we constructed an acid-improved DNAzyme-based isothermal enzyme-free concatenated DNA circuit with significantly reduced background and simultaneously improved signal-to-noise ratio for miRNA detection. The chemiluminescence miRNA assay is composed of catalyzed hairpin assembly (CHA), hybridization chain reaction (HCR), and hemin/G-quadruplex DNAzyme units. The analyte initiates the self-assembly of CHA hairpins into numerous dsDNA, which triggers the subsequent autonomous cross-opening of HCR hairpins to generate long nanowires consisting of the hemin/G-quadruplex DNAzyme. The DNAzyme catalyzes the oxidation of luminol by hydrogen peroxide for the cascaded amplified chemiluminescence signal. The acid-improved property was demonstrated to be closely associated with the low catalytic activity of aggregated hemin under acidic conditions and the remained multiple amplified signal through concatenated DNA circuit. The general DNA circuit exhibited high sensitivity for miRNA-21 detection and chemiluminescence imaging under acidic conditions with a recognition hairpin. The acid-improved DNAzyme-based concatenated DNA circuit is promising to expand the application of chemiluminescence assay and provide a valuable strategy for early diagnosis and prognosis of cancer.

Selective profiling of steviol-catalyzing UDP-glycosyltransferases in plants was accomplished with a probe metabolically synthesized from two substrate-derived components comprising an alkynylated sugar receptor (steviol) module and a diazirine-modified sugar donor (UDP-glucose) module, thereby illustrating a facile approach for harnessing biosynthetic enzymes of natural glycosides in plants for synthetic biology.

Cancer cells rely on fatty acid synthase (FASN), a key enzyme for de novo biosynthesis of long chain fatty acids, to sustain their proliferative potential and drive invasion. Unfortunately, conventional FASN assays are technically inadequate for discerning otherwise elusive FASN activity in complex biological milieux, which has hindered progress in the functional study of FASN and development of its inhibitors. Here, we describe a chemical probe with unprecedented selectivity and sensitivity for the labeling of active FASN in living cells, thus demonstrating a new analytical modality for visualizing endogenous FASN activity and exploring opportunities for drug discovery.

Natural-product macrolide 10,11-dehydrocurvularin (DCV) was revealed to be a potent irreversible inhibitor of ATP-citrate lyase (ACLY) via classical chemoproteomic profiling, which mechanistically illuminates the anti-cancer mode of action of DCV and its analogues.

A new α-pyrone derivative1, along with four known congeners 2, 3, 4 and 5, were isolated from the solid-substrate fermentation medium of the endophytic fungus Pestalotiopsis microspore isolated from the branch of Taxus chinensis. Their structures and relative configurations were elucidated by extensive spectroscopic analysis. The cytotoxic activities of the isolated α-pyrone derivatives against two tumor cell lines as well as compound 1 ’ s antimicrobial activity against three bacteria and three plant-pathogenic strains were evaluated. No antimicrobial activity was observed for compound 1. The cytotoxicity against Caski and He L a tumor cell lines w as insignificant. To our surprise, the known compound 4 showed significant gibberellin synergistic activity towards Distylium chinense seeds.

Hispolon was the main antitumor active ingredient in Phellinus sensu lato species. In order to confirm the dual regulating estrogenic ingredient and obtain more effective natural estrogen replacement drugs, hispolon was separated from Phellinus lonicerinus (Bond.) Bond. et sing. Hispolon exhibited significant anti-proliferative effect against estrogen-sensitive ER (+) MCF-7 cells in the absence of estrogen, and exhibits antagonistic effects on 17β-estradiol (E2)-induced MCF-7 cell proliferation when E2 and the different concentrations of hispolon were treated simultaneously. Hispolon also inhibited the proliferation of estrogen-negative ER (−) MDA-MB-231 cells at the concentration of 5.00 × 10− 5 M. The yeast two-hybrid experiments showed that hispolon had strong and non-selective effects on the estrogen receptor (ER) α and ERβ at a concentration of 1.00 × 10− 6 M. The ERβ-binding ability of hispolon was larger than ERα in the concentration range of 1.00 × 10− 9 M and 1.00 × 10− 7 M. Hispolon could increase the body weight coefficient, serum E2 and progesterone contents in immature female mice at dose of 9.10 × 10− 6 mol/kg, and increase coefficient of thymus and spleen in mice. The Gscores of hispolon-ERα and hispolon-ERβ docked complexes were − 7.93 kcal/mol and − 7.79 kcal/mol in docking simulations. Hispolon presented dual regulating estrogenic activities, which showed estrogenic agonist activity at low concentration or lack of endogenous estrogen, and the estrogenic antagonistic effect was stimulated at high concentrations or too much endogenous estrogen. Hispolon could be used for treating the estrogen deficiency-related disease with the benefit of non-toxic to normal cells, good antitumor effects and estrogenic activity.

A highly solid-emissive Boron–Fluorine scaffold with two conjugated alkyne groups ( BOPIM-S ) is facilely synthesized, which shows enhanced fluorescent intensity compared to the BOPIM dye without alkyne units. According to X-ray single crystal analysis, the terminal alkyne groups interact with atoms B, F, C and N on neighbouring molecules, producing a rigid rectangular structure, which helps to avoid energy loss via non-irradiative decay. Furthermore, BOPIM-S can undergo copper catalysed alkyne–azide-cycloaddition (CuAAC) chemistry with aromatic azides to produce conjugated molecules with high yields. According to absorption and fluorescent measurements, all these compounds synthesized by CuAAC emit large Stokes shift (over 100 nm) both in solution and in solid state. But the electronic environments of terminal aromatic rings slightly affect their photophysical properties.

(-)-(10E,15S)-10,11-Dehydrocurvularin (1), produced from an associated-fungus of Scolopendra subspinipes mutilans on a gram scale, was microbiologically converted to curvularin (2) and 5-methoxycurvularin (3) by Antrodiella semisupina in 61% totally isolated yield. The structures of these compounds were elucidated on the basis of spectroscopic and mass spectrometric analysis. The undescribed assignments of 1H and 13C NMR spectral data for 5-methoxycurvularin (2) has now been explicitly provided. The cytotoxic activities of compounds 1-3 against four human cancer cell lines were evaluated. Dehydrocurvularin (1) showed moderate cytotoxicity against Caski and Hep-G2, and curvularin (2) was selectively cytotoxic against MDA-MB-231.

Three new furostanol saponins (1-3), including a polyhydroxyl saponin, were isolated from the rhizomes of Tupistra chinensis. The structures of these compounds were identified by NMR, MS spectral data and chemical methods.