Inhibition of DNA Topoisomerase Ι by Flavonoids and Polyacetylenes Isolated from Bidens pilosa L.

Human DNA topoisomerase I (Topo I) is an essential enzyme in regulating DNA supercoiling during transcription and replication, and it is an important therapeutic target for anti-tumor agents. Bidens pilosa L. is a medicinal herb that is used as a folk medicine for cancers in China. A new flavonoid (1) and a new polyacetylene (20), along with eighteen flavonoids (2-19) and nine polyacetylenes (21-29), were isolated and identified from the methanol extract of the whole plant of B. pilosa, and some of the compounds (4, 5, 6 and 7) exhibited potent cytotoxicity against a panel of five human cancer cell lines. The DNA relaxation assay revealed that some flavonoids and polyacetylenes exerted inhibitory activities on human DNA Topo I, among them compounds 1, 2, 5, 6, 7, 8, 15, 19, 20, 22, and 24 were the most active ones, with IC50 values of 393.5, 328.98, 145.57, 239.27, 224.38, 189.84, 89.91, 47.5, 301.32, 178.03, and 218.27 µM, respectively. The structure-activity analysis of flavonoids was performed according to the results from the Topo I inhibition assay. The DNA content analysis revealed that 5, 6, and 7 potently arrested cell cycle at the G1/S and G2/M phases in human colon cancer cell DLD-1 depending on the concentration of the inhibitors. The levels of protein expression related to the G1/S and G2/M cell cycle checkpoints were in accordance with the results from the DNA content analysis. These findings suggest that flavonoids are one of the key active ingredients accounting for the anti-tumor effect of B. pilosa.

Cytotoxic and anti-inflammatory polyacetylenes from Tridax procumbens L.

Herein, 17 previously undescribed polyacetylenes and 9 known ones were isolated from Tridax procumbens L. Their structures were identified using spectroscopic techniques (NMR, UV, IR, MS and optical rotation), the modified Mosher method, electronic circular dichroism (ECD) data and ECD calculation. The cytotoxicity of polyacetylenes on six human tumour cell lines (K562, K562/ADR, AGS, MGC-803, SPC-A-1 and MDA-MB-231) was evaluated. (3S,10R)-tridaxin B (2a), (3S,10S)-tridaxin B (2b) and tridaxin F (8) demonstrated substantial cytotoxic effects against the K562 cell line, with half-maximal inhibitory concentration (IC50) values of 2.62, 14.43 and 17.91 µM, respectively. Cell and nucleus morphology assessments and Western blot analysis confirmed that the cytotoxicity of the three polyacetylenes on K562 cells was mediated through a dose-dependent apoptosis pathway. Furthermore, (3S,10R)-tridaxin A (1a) and tridaxin G (9) exhibited considerable inhibitory effects on lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages, with IC50 values of 15.92 and 20.35 µM, respectively. Further investigations revealed that 9 exerted anti-inflammatory activities by impeding the nuclear translocation of NF-κB and down-regulating the expression of pro-inflammatory factors, including those of iNOS, COX-2, IL-1ß and IL-6, in a concentration-dependent manner. The study provides evidence that polyacetylenes from T. procumbens may serve as a potential source of anti-tumour or anti-inflammatory agents for treating related diseases.

Artemdubosides A-G, seven unusual polyacetylenes from Artemisia dubia var. subdigitata and their antihepatoma activity.

Artemdubosides A-E (1-5), the first examples of natural polyacetylenes substituted by 6'-O-crotonyl ß-glucopyranoside, and artemdubosides F-G (6-7) that were two unusual polyacetylenes featuring a 6'-O-acetyl ß-glucopyranoside moiety, were isolated from Artemisia dubia var. subdigitata. Their structures were elucidated based on the spectral data including HRESIMS, UV, IR, 1D and 2D NMR, and ECD calculations. Antihepatoma assay suggested that compound 1 exhibited activity against HepG2, Huh7, and SK-Hep-1 cells with inhibitory ratios of 77.1%, 90.8%, and 73.1% at 200.0 µM, respectively.

Polyacetylenes from Saposhnikovia divaricata and their anticancer activity.

Nine polyacetylenes, including five new compounds named sadivaethynes E-I (1-5), were isolated from the roots of Saposhnikovia divaricata. Structural elucidation of compounds 1-5 was established by extensive spectroscopic analysis, quantum chemical calculations and DP4+ probability analysis. Among them, the absolute configuration of compound 1-2, 4-5 was unambiguous determined by ECD. Also, all compounds were evaluated for cytotoxicity against two human cancer cell lines (A549, HEPG2) in vitro, compound 9 showed moderate inhibitory effect with an IC50 value of 11.66 µM against HEPG2.

Bacterial polyynes uncovered: a journey through their bioactive properties, biosynthetic mechanisms, and sustainable production strategies.

Covering: up to 2023Conjugated polyynes are natural compounds characterized by alternating single and triple carbon-carbon bonds, endowing them with distinct physicochemical traits and a range of biological activities. While traditionally sourced mainly from plants, recent investigations have revealed many compounds originating from bacterial strains. This review synthesizes current research on bacterial-derived conjugated polyynes, delving into their biosynthetic routes, underscoring the variety in their molecular structures, and examining their potential applications in biotechnology. Additionally, we outline future directions for metabolic and protein engineering to establish more robust and stable platforms for their production.

Polyacetylene Derivatives from the Polypore Fungus (Fistulina hepatica, Agaricomycetes) and Their Antimicrobial Activity.

Chemical investigation of the polypore fungus Fistulina hepatica resulted in the isolation of five compounds, including four new polyacetylenic fatty acid derivatives - isocinnatriacetin B (1), isocinnatriacetin A (2), cinna-triacetin C (3) and ethylcinnatriacetin A (4) together with one known polyacetylene fatty acid derivative - cinnatriacetin A (5). The structures were elucidated using spectroscopic methods (UV, NMR, HR-ESIMS) along with comparison to literature data. Antibacterial activity screening of compounds 1-5 against ESKAPE bacterial strains in vitro with zones of inhibition (ZOI) was performed and MIC values were established for the most active compounds (3 and 4). Together with that morphological and growth parameters under solid-phase cultivation were also researched.

Polyacetylenes with xanthine oxidase inhibitory activity from the medicinal and edible fruits of Cyclocodon lancifolius (Roxburgh) Kurz.

Five new polyacetylene derivatives (1-5), cyclocodonlandiynosides A-E, and eight known analogues (6-13) were isolated and identified from the fruits of Cyclocodon lancifolius. Their structures were established via spectroscopic and chemical methods, including NMR, HRESIMS, enzymatic hydrolysis, Mo2(OAc)4-induced circular dichroism and sugar derivatization. Compound 1 contains a nitrogenous fragment, which was rarely found in C14 polyacetylenes. Compounds 3 and 4 are polyacetylene glucosides possessing novel aglycones. All the isolated polyacetylenes (except 12) were screened for their xanthine oxidase (XO) inhibitory activity. All the tested compounds, at the concentration of 62.5 µg/mL, showed XO inhibiting effects. Among them, 13 and 3 showed the most potent XO inhibitory activity with IC50 values of 87.65 and 96.32 µM, compared to the positive control allopurinol with an IC50 value of 19.25 µM.

Elemane-Type Sesquiterpene, Acetonide Derived Polyacetylene and Other Constituents from the Whole Plant of Gymnanthemum theophrastifolium (Schweinf. ex Oliv. & Hiern) H.Rob. and Their Chemophenetic Significance.

The chemical investigation of the methanol extract of the whole plant of Gymnanthemum theophrastifolium (Schweinf. ex Oliv. & Hiern) H.Rob. (Asteraceae) led to the isolation of a new elemane-type sesquiterpene (1), a new acetonide derived polyacetylene (2) and a naturally occurring compound (3) from the plant kingdom along with sixteen known compounds (4-19). Their structures were elucidated by extensive NMR and MS analysis. This is the first report on the chemical constituents of G. theophrastifolium. Furthermore, compounds 12, 13, and 14 are reported for the first time from the family Asteraceae, while compound 9 is reported for the first time from the genus Gymnanthemum. Thus, the present results provide valuable insights to the chemophenetic knowledge of G. theophrastifolium, which is also discussed in this work.

Cytotoxic Properties of C17 Polyacetylenes from the Fresh Roots of Panax ginseng on Human Epithelial Ovarian Cancer Cells.

Although C17 polyacetylenes from Panax ginseng exhibit cytotoxic properties against various tumor cells, there have been few experiments on epithelial ovarian carcinoma cells. This study aimed to investigate the cytotoxic effects of C17 polyacetylenes from P. ginseng against ovarian cancer cell lines. Four unreported (1-4) and fifteen known (5-19) C17 polyacetylenes were obtained from the roots of P. ginseng using repeated chromatography (open column, MPLC, and preparative HPLC). The chemical structures of all the compounds were determined by analyzing their spectroscopic data (NMR, IR, and optical rotation) and HR-MS. The structures of new polyacetylenes were elucidated as (3S,8S,9R,10R)-(-)-heptadeca-9,10-epoxy-4,6-diyne-3,8-diyl diacetate (1), (3S,8S,9R,10R)-(-)-heptadeca-1-en-9,10-epoxy-4,6-diyne-3,8-diyl diacetate (2), (-)-haptadeca-9,10-epoxy-8-methoxy-4,6-diyne-3,11-diol (3), and (3R,9R,10R)-(+)-3-acetoxy-9,10-dihydroxyheptadeca-1-en-4,6-diyne (4), named ginsenoynes O, P, and Q, and 3-acetyl panaxytriol, respectively. Subsequently, in vitro experiments on A2780 and SKOV3 human epithelial ovarian carcinoma cells were performed to assess the cytotoxic properties of the isolates. Among the isolates, panaquinquecol 4 (15) exhibited the most remarkable cytotoxic effects on both human ovarian cancer cells A2780 (IC50 value of 7.60 µM) and SKOV3 (IC50 value of 27.53 µM). Therefore, C17 polyacetylenes derived from P. ginseng may warrant further investigation for their therapeutic potential in epithelial ovarian cancer.

Anticholinesterase Compounds from Endemic Prangos uechtritzii.

In this study, the anticholinesterase effects of the extracts and isolated compounds from the roots of endemic Prangos uechtritzii Boiss & Hausskn (Apiaceae) are reported. A novel polyacetylenic compound; (+)-8-O-methyloplopantriol A along with two known polyacetylenes; (-)-panaxynol, (+)-falcarindiol and fifteen known coumarin derivatives; umbelliferone, 6-formylumbelliferone, suberosin, 7-demethylsuberosin, (+)-ulopterol, tamarin, psoralen, imperatorin, (+)-oxypeucedanin, (+)-oxypeucedanin hydrate, (+)-oxypeucedanin methanolate, (+)-marmesin, (-)-prantschimgin, (+)-decursinol, and (-)-adicardin were isolated from the hexane (Pu-HE), chloroform (Pu-CE), and methanol (Pu-ME) extracts of P. uechtritzii roots. (-)-Panaxynol, (+)-falcarindiol, 6-formylumbelliferone, (+)-decursinol, and (-)-adicardin were obtained from the genus Prangos for the first time. (+)-8-O-Methyloplopantriol A inhibited both AChE (IC50 =194.5±5.8 µM) and BChE (IC50 =51.9±2.96 µM) enzymes. (+)-Falcarindiol, 6-formylumbelliferone, 7-demethylsuberosin, tamarin, and imperatorin also exhibited BChE-specific inhibitory activities (IC50 =27.88-93.86 µM). (+)-Falcarindiol (IC50 =27.88±0.91 µM) and imperatorin (IC50 =30.89±1.40 µM) as the most active components could be led compounds to develop new BChE inhibitors with further research against Alzheimer's disease.

Polyacetylenes from the roots of Cirsium japonicum var. ussuriense.

Eight previously undescribed polyacetylenes, cirussurynes A-H, were isolated from the methanolic extract of the roots of Cirsium japonicum var. ussuriense. Their structures were elucidated by interpretation of extensive 1D and 2D NMR spectroscopy and HRESIMS spectrometry data. The configuration of triols in cirussurynes A, B, and E-G was deduced by the J-value based configuration analysis together with specific rotation values. All compounds were evaluated for their inhibitory effects on nitric oxide production against LPS-induced RAW 264.7 macrophages, and exhibited IC50 values ranging from 5.5 to 68.7 µM.

Diverse polyacetylenes from Atractylodes chinensis and their anti-osteoclastogenesis activity.

The phytochemical investigation on Atractylodes chinensis afforded 15 polyacetylenes 1-15 and one meroterpenoid 16. Of the 16 isolates, compounds 4 and 9 are new ones, and compounds 8 and 16 are first reported from nature. In addition, the relative configuration of 1 and the available NMR data of compounds 1, 8, and 16 were first provided. Their structures were elucidated by extensive analysis of MS, UV, IR, and NMR spectroscopic data. Besides, all isolated compounds were evaluated for their effects on RANKL-induced osteoclastogenesis in BMMs. Among them, polyacetylenes 12-14 showed potent inhibitory activity with IC50 values of 0.67 ± 0.05 µM, 0.72 ± 0.31 µM, and 2.40 ± 0.41 µM, respectively. The current work demonstrates the polyacetylenes are the main active constituents of A. chinensis against osteoclastogenesis.

Polyacetylenes in herbal medicine: A comprehensive review of its occurrence, pharmacology, toxicology, and pharmacokinetics (2014-2021).

Polyacetylenes are a kind of small active compounds with carbon-carbon triple bond with vast occurrence in plants. Polyacetylenes have attracted considerable attention owing to their diverse biofunctions like tumor suppression, immunity regulation, depression resistance and neural protection. The present review intends to reconstruct data concerning the occurrence, pharmacology, toxicology and pharmacokinetics of polyacetylenes from herbal medicine in a systematic and integrated way, with a view to backing up their curative potential and healthcare properties (2014-2021). The natural polyacetylene-related data were all acquired from the scientific search engines and databases that are globally recognized, such as PubMed, Web of Science, Elsevier, Google Scholar, ResearchGate, SciFindern and CNKI. A total of 183 polyacetylenes were summarized in this paper. Modern pharmacological studies indicated that polyacetylenes possess multiple biological activities including antitumor, immunomodulatory, neuroprotective, anti-depression, anti-obesity, hypoglycemic, antiviral, antibacterial, antifungal, hepatoprotective and renoprotective activities. As important bioactive components of herbal medicine, the pharmacological curative potential of polyacetylenes has been described against carcinomas, inflammatory responses, central nervous system, endocrine disorders and microbial infection in this review. While, further in-depth studies on the aspects of polyacetylenes for toxicity, pharmacokinetics, and molecular mechanisms are still limited, thereby intensive research and assessments should be performed.

Integrated omics approach to unveil antifungal bacterial polyynes as acetyl-CoA acetyltransferase inhibitors.

Bacterial polyynes are highly active natural products with a broad spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. By integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), in the biosynthesis gene cluster of antifungal polyynes (massilin A 1, massilin B 2, collimonin C 3, and collimonin D 4) of Massilia sp. YMA4. Crystallographic analysis indicated that bacterial polyynes serve as covalent inhibitors of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited the cell viability of Candida albicans by targeting ERG10, the homolog of MasL. Thus, this study demonstrated that acetyl-CoA acetyltransferase is a potential target for developing antifungal agents.

New Bioactive Polyacetylenes from the Marine Sponge Petrosia sp.

Three new polyacetylenes, pellynols P (1), Q (2), and R (3) were isolated from the marine sponge Petrosia sp., along with the known compound pellynol H (4). Their structures were determined by analyses of extensive NMR, HR-MS, and ESI-MS/MS data. All compounds displayed potent cytotoxicities against human hepatocellular carcinoma HepG2, human melanoma A375, and human colorectal carcinoma HT29 cell lines with IC50 values at the range of 1.4-4.4 µM.

Diverse Sesquiterpenoids and Polyacetylenes from Atractylodes lancea and Their Anti-Osteoclastogenesis Activity.

Twenty-two sesquiterpenoids (1-22) and 11 polyacetylenes (23-33) were obtained from the rhizomes of Atractylodes lancea. Among them, 11 compounds (1-5, 11, 12, 23, 24, 30, and 31) are new. The scaffolds represented by the isolates of sesquiterpenoids were found to be varied and included two rare rearranged spirovetivane sesquiterpenoids with a spiro [4,4] skeleton, eight spirovetivanes, three guaianes, eight eudesmanes, and one eremophilane. Their planar structures and relative configurations were elucidated by UV, IR, 1D and 2D NMR, and HRESIMS data analysis. The absolute configurations of the new sesquiterpenoids were determined using X-ray diffraction analysis and by comparison of the calculated and experimental electronic circular dichroism and optical rotation data, as well as chemical transformations. All the isolated compounds (1-33) were evaluated for their activity against RANKL-induced osteoclastogenesis in bone marrow macrophages. Two polyacetylene-type compounds, 25 and 32, showed potent activity with IC50 values of 1.3 and 0.64 µM, respectively. Rearranged spirovetivane sesquiterpenoids with a spiro [4,4] skeleton are reported herein from the genus Atractylodes for the first time. Polyacetylenes were demonstrated as the main active constituents of A. lancea with osteoclastogenesis inhibitory activity.

Bioactive polyacetylenes from Bidens pilosa L and their anti-inflammatory activity.

A new polyacetylenic glucoside together with three known compounds were isolated from the whole herb of Bidens pilosa L. The structure elucidation of these four compounds was employed by combining NMR and HR-MS data as 4-O-ß-D-glucopyranosyloxy-1-hydroxy- 6-(E)-tetradecene-8,10,12-triyne (1), 3-O-ß-D-glucopyranosyloxy-1-hydroxy-6-(E)-tetradec- ene-8,10,12-triyne (2), 2-O-ß-D-glucopyranosyloxy-1-hydroxy-5-(E)-tetradecene-7,9,11-triy- ne (3) and icthyothereol acetate (4). Additionally, bioactivity study showed that these compounds have potential anti-inflammatory activity. This study has certain guiding significance for the development and utilisation of polyacetylene compounds in Bidens pilosa L.

Isolobetyol, a new polyacetylene derivative from Platycodon grandiflorum root.

A new polyacetylene, namely isolobetyol (1), was isolated from the root of Platycodon grandiflorum (Jacq.) A. DC., together with lobetyol (2), lobetyolin (3), and trans-2-hexenyl ß-D-glucoside (4). The structures of the isolated natural products were identified by high-resolution mass spectrometric (HR-MS) and nuclear magnetic resonance (NMR) spectroscopic analyses. The obtained spectroscopic data was in good agreement with the data previously reported in the literature. The anti-proliferative effects of the isolated compounds were examined using the PC-3 prostate cancer cell line. Compounds 1-3 considerably reduced the proliferation of the PC-3 cells with IC50 values of 6.76, 12.72, and 5.73 µM, respectively.

Four new polyacetylenes from the roots of Saposhnikovia divaricata.

Four new polyacetylene substances, sadivaethynes A-D, were isolated from the ethanol extract of the roots of Saposhnikovia divaricata (Turcz.) Schischk using repeated column chromatography. Structural elucidation of compounds 1-4 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for cytotoxicity against two human cancer cell lines (MGC-803, Ishikawa) in vitro.

Three new polyacetylenes from Atractylodes japonica Koidz.ez Kitam.

Three new polyacetylenes (1-3), together with six known polyacetylenes (4-9), were isolated from a 95% aqueous ethanol extract of the Atractylodes japonica Koidz.ez Kitam. Their structures were elucidated by HR-ESI -MS and NMR techniques as well as comparison with those reported in literatures. The cytotoxic activity of 1-3 were also evaluated.