Journal of Natural Products 最新文献

The tropical plant Aglaia perviridis is known to produce cyclopenta[b]benzofuran and other types of rocaglate derivatives including silvestrol (3) and 5‴-episilvestrol (4) that are of current pharmacological interest. In the present work, further investigation of A. perviridis roots collected in Vietnam has yielded two new rocaglate acetonide derivatives (1 and 2) and a known pentanor-3,4-seco-dammarane triterpenoid (7) found for the first time as a natural product, in addition to four known rocaglates (3-6). The structures of compounds 1 and 2 were confirmed by partial synthesis experiments, and their potential occurrence as extraction artifacts was investigated by targeted selective ion monitoring using UHPLC-MS. All compounds obtained were evaluated against a panel of four human cancer cell lines, in which the six rocaglate derivatives (1-6) tested all showed submicromolar potencies.

Twelve guanidine derivatives (1-12), including seven new compounds (martensiiagms A-G, 1-7), one new hypoxanthine derivative (martensiiagm H, 13), and 15 known compounds (14-28) were isolated from the whole body of Buthus martensii Karsch and identified by analysis of data. Subsequent biological evaluations revealed the anti-inflammatory activity of compound 1. It attenuates the neuroinflammation and oxidative stress levels prompted by lipopolysaccharide. This attenuation is accomplished by a specific action on mitochondria, which, in turn, caused a significant decrease in reactive oxygen species and pro-inflammatory cytokines.

The recent popularity of indoor farming has brought about problems with parasites spreading among pollinator colonies. The natural product callunene (1) can be used in the prophylaxis of bumblebees against Crithidia infection. Here, we report the synthesis of callunene (1), its enantioseparation, and a method for analyzing its optical purity. The approach was applied to determine the configuration of callunene extracted from heather honey. The proposed method is also applicable to the analysis of mixtures of diastereomers obtained during callunene synthesis, which allows the stereospecificity of individual reaction steps to be determined.

Bibenzyls and dihydrophenanthrenes exhibit promising immunomodulatory effects in various human diseases. In this study, we isolated one new dihydrophenanthrene derivative (1), two new bibenzyl-dihydrophenanthrene derivatives (2, 3) along with 12 known compounds (4-15) from the methanol extract of Calanthe cardioglossa. These compounds were identified by using physicochemical analyses and spectroscopic methods. The three new compounds possess enantiomeric forms, and their configurations were determined by comparing the experimental electronic circular dichroism (ECD) spectra to data from the literature. The immunomodulatory activity of the isolated compounds was assessed in THP-1 monocytes and human peripheral blood mononuclear cells (PBMCs) derived from multiple sclerosis (MS) patients. Notably, five of the isolated compounds significantly reduced the TNF-α levels in LPS-stimulated THP-1 monocytes. Furthermore, calancardin B (2) exhibited a significant reduction in TNF-α levels in both THP-1 monocytes and CD14⁺ monocytes from MS PBMCs.

Monascus pigments having yellow, orange, and red colors are widely studied for their potential beneficial properties. Many different biological activities have been reported regarding Monascus pigments and their derivatives, but the usual method is to test complex extracts from the mycelium of the fungus or from a fungus-fermented substrate. However, this review is mainly concerned with the biological activities of purified Monascus pigments. Both yellow (ankaflavin, monascin) and red (rubropunctamine, monascorubramine) Monascus pigments are proven antioxidants if used in concentrations of 10 μg/mL or higher. Antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi has been observed with all Monascus pigments. However, the best antimicrobials are red Monascus pigments, and their amino acid derivatives (l-cysteine derivatives have MIC 4 μg/mL against Enterococcus faecalis). Yellow monaphilones and orange monaphilols seem to have the highest anti-inflammatory activity (IC₅₀ 1.7 μM of monaphilol D) and, together with red Monascus pigment derivatives, have mild antiobesity and antidiabetic activities. Further, monascin and ankaflavin in daily doses of 0.5 and 0.08 mg, respectively, lowered serum blood levels of low-density lipoprotein cholesterol complexes in rats on a high-fat diet. Orange Monascus pigments, rubropunctatin and monaphilols A and C, exhibit cytotoxic and antitumor activities (IC₅₀ 8-10 μM).

Ten previously undescribed iridoid glycosides (1-10), including monoiridoids, hybrid iridoid-alkaloids, bis-iridoids, noriridoid-iridoid dimers, and tetramers, were isolated from the roots of Gomphandra mollis Merr. Structural elucidation revealed unique sugar chains not previously observed for iridoids and complex tetrameric configurations that are rare in nature. Compounds 9, 10, and 15 demonstrated significant anti-inflammatory effects, with IC₅₀ values ranging from 6.13 to 13.0 μM, and compounds 6, 7, and 11-13 showed notable hepatoprotective activity in HepG2 cells. Additionally, structure-activity relationship (SAR) analysis on anti-inflammatory effects was also conducted. This study enriches the structural database of iridoids, particularly complex derivatives, and highlights their therapeutic potential in addressing inflammation-related and liver diseases.

Ferroptosis is a type of regulated cell death driven by the iron-dependent accumulation of lipid peroxides. The high involvement of ferroptosis in diverse human diseases highlights the need for the identification of new chemotypes with anti-ferroptotic activity. Here, we performed a natural product library screening in HT1080 fibrosarcoma cells and identified licochalcone A (LA), isoeugenyl acetate (ISA), and isoliensinine (ISL) as suppressors of either RSL3- or IKE-induced ferroptosis. Mechanistically, ferroptosis resistance conferred by these compounds is mainly through GPX4/NRF2-independent mechanisms. Among them, only ISL could effectively rescue ferroptosis induced by FINO₂, which is a stable oxidant of ferrous iron, suggesting that ISL may have the properties of an iron chelator. Consistent with the hypothesis, both computational tools and X-ray photoelectron spectroscopy supported the binding between ISL and iron ions. And ISL greatly inhibited excessive iron-dependent ferroptotic cell death through limiting intracellular iron accumulation. Furthermore, its iron chelator activity also protected mice from organ injury in an acute iron overload model. In conclusion, this study provided valuable insights for developing effective anti-ferroptosis agents from natural products, which represent a potential therapeutic strategy for treating ferroptosis-associated organ damage.

The first enantioselective total synthesis and structure revision of isolophanthin E and syntheses of proposed structures of isolophanthins A, B, and C are demonstrated. Natural product 3β-hydroxy-8,11,13,15-abietatetraene was directly synthesized utilizing an efficient cationic polyene cyclization, and it is used as a common intermediate in the synthesis of isolophanthins and related abietatriene natural products. Two distinct synthetic routes were established for the synthesis of different stereoisomers of isolophanthin E. Spectroscopic analysis and structural assignment of isolophanthin E stereoisomers provide valuable insights into the relative configuration of the C-2, C-3-dihydroxy A ring of similar terpenoids, aiding in the identification of their configuration. A total of seven diterpenoids were obtained using regioselective chloromethylation, Sharpless dihydroxylation, Cu(II) catalyzed allyl-benzyl coupling, epoxide-initiated polyene cyclization, Rubottom oxidation, and additive-controlled dihydroxylation as key synthetic steps.

trans-Fagaramide (1) and adubangoamide (2) are natural products with a cinnamic acid amide skeleton that have recently been isolated from Zanthoxylum leprieurii, a medicinal plant used locally in Uganda for the treatment of tuberculosis. Insufficient quantities of material from the natural source originally prevented the antimycobacterial evaluation of the new natural product 2. Herein, a synthesis of 2 is reported, and its antimycobacterial activity was determined using the synthetic material. Adubangoamide (2) is three times more active against the drug-susceptible M. tuberculosis strain H₃₇Rv than trans-fagaramide (1), with an MIC value of 10.0 μM. In addition, we synthesized eight non-natural analogues of trans-fagaramide (1, MIC = 32.0 μM against H₃₇Rv strain), in which benzylamide groups mimic the isobutylamide part of the trans-fagaramide structure. Five out of eight synthetic analogues are more active than the parent natural product: 11b (MIC = 6.0 μM), 11d (21.0 μM), 11e (6.1 μM), 11g (17.0 μM), and 11h (4.5 μM).