Search Results (19)

Grossheimin, a guaiane-type sesquiterpene lactone, displayed a diverse range of biological activities, including anticancer, anti-inflammatory and antimicrobial effects. Various amino analogues of grossheimin were prepared through a Michael addition at its highly active α-methylene-γ-lactone motif. On the other hand, grossheimin was reduced to diol, which was then subjected to nucleophilic addition or acetylation to introduce heteroatoms associated with oxygen, sulfur or nitrogen functionalities. All of the synthesised Michael and acetylated adducts were evaluated for their in vitro cytotoxic action on human colon adenocarcinoma lines, including Colo205 and Colo320. The bioassay results indicated that the acetylated adducts displayed a potent cytotoxic effect compared to grossheimin, the parent molecule. A docking study was also performed to exploit the observed results. Full article

Sesquiterpenes constitute the principal components of the genus Ainsliaea, encompassing guaiane, germacrane, eudesmane, and polymer sesquiterpene lactones types. These secondary metabolites exhibit diverse pharmacological activities, including antitumor, antibacterial, anti-inflammatory, antiviral, antioxidant, hepatoprotective, and neuroprotective effects. Through a comprehensive literature search of the Web of Science, PubMed, SciFinder, and CNKI databases, it was discovered that there are as many as 145 main sesquiterpenoids in the genus Ainsliaea. However, the nuclear magnetic resonance (NMR) data for the sesquiterpenes in this genus have not been systematically compiled and summarized. Therefore, this review aims to highlight the chemical structures, NMR data, and pharmacological activities of sesquiterpenes in Ainsliaea. By meticulously analyzing published scholarly literature, our goal is to provide a solid foundation for further exploration of new sesquiterpenes and extensive utilization of this genus. Full article

Curcumae Rhizoma, a traditional Chinese medicine with a wide range of pharmacological activities, is obtained from the dried rhizomes of Curcuma phaeocaulis VaL., Curcuma kwangsiensis S. G. Lee et C. F. Liang, and Curcuma wenyujin Y. H. Chen et C. Ling. Sesquiterpenoids and curcuminoids are found to be the main constituents of Curcumae Rhizoma. Sesquiterpenoids are composed of three isoprene units and are susceptible to complex transformations, such as cyclization, rearrangement, and oxidation. They are the most structurally diverse class of plant-based natural products with a wide range of biological activities and are widely found in nature. In recent years, scholars have conducted abundant studies on the structures and pharmacological properties of components of Curcumae Rhizoma. This article elucidates the chemical structures, medicinal properties, and biological properties of the sesquiterpenoids (a total of 274 compounds) isolated from Curcumae Rhizoma. We summarized extraction and isolation methods for sesquiterpenoids, established a chemical component library of sesquiterpenoids in Curcumae Rhizoma, and analyzed structural variances among sesquiterpenoids sourced from Curcumae Rhizoma of diverse botanical origins. Furthermore, our investigation reveals a diverse array of sesquiterpenoid types, encompassing guaiane-type, germacrane-type, eudesmane-type, elemane-type, cadinane-type, carane-type, bisabolane-type, humulane-type, and other types, emphasizing the relationship between structural diversity and activity. We hope to provide a valuable reference for further research and exploitation and pave the way for the development of new drugs derived from medicinal plants. Full article

Sesquiterpenoids, an important class of natural products possessing three isoprene-derived units, are widely distributed across plants and have a variety of biological activities. All sesquiterpenoids are derived from farnesyl pyrophosphate (FPP), a biosynthesis precursor that can form various carbon skeletons. In order to provide a reference for further research and development of these compounds, this review focused on the increasing number of isolated and volatile sesquiterpenoids found to be produced by plants of the Meliaceae family between 1968 and 2023. The related articles were collected from SciFinder, Google Scholar, and PubMed. According to a literature review, several studies were started for more than 55 years on the plant’s stem barks, twigs, leaves, flowers, seeds, and pericarps, where approximately 413 sesquiterpenoid compounds from several groups such as eudesmane, aromadendrane, cadinane, guaiane, bisabolane, furanoeremophilane, humulene, germacrane, and oppositane-type were isolated and identified with some minor products. Additionally, the hypothetical route of sesquiterpenoids biosynthesis from this family was identified, and eudesmane-type was reported to be 27% of the total compounds. The antimicrobial, antidiabetic, antioxidant, antiplasmodial, antiviral, and cytotoxic activities of the isolated compounds and major volatile sesquiterpenoids constituent on essential oil were also evaluated. The result showed the fundamental of using the sesquiterpenoid compounds from the Meliaceae family in traditional medicine and the discovery of new drugs. Full article

Seven undescribed guaiane-type sesquiterpenoids named biscogniauxiaols A–G (1–7) were isolated from the endophytic fungus Biscogniauxia petrensis on Dendrobium orchids. Their structures were determined by extensive spectroscopic analyses, electronic circular dichroism (EC) and specific rotation (SR) calculations. Compound 1 represented a new family of guaiane-type sesquiterpenoids featuring an unprecedented [5/6/6/7] tetracyclic system. A plausible biosynthetic pathway for compounds 1–7 was proposed. The anti-fungal, anti-inflammatory and multidrug resistance reversal activities of the isolates were evaluated. Compounds 1, 2 and 7 exhibited potent inhibitory activities against Candida albicans with MIC values ranging from 1.60 to 6.30 μM, and suppressed nitric oxide (NO) production with IC₅₀ ranging from 4.60 to 20.00 μM. Additionally, all compounds (100 μg/mL) enhanced the cytotoxicity of cisplatin in cisplatin-resistant non-small cell lung cancer cells (A549/DDP). This study opened up a new source for obtaining bioactive guaiane-type sesquiterpenoids and compounds 1, 2, and 7 were promising for further optimization as multifunctional inhibitors for anti-fungal (C. albicans) and anti-inflammatory purposes. Full article

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as “the king of cancers”. Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from Nardostachys jatamansi DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer. Full article

Two new guaiane sesquiterpenes, aquisinenoids A and B (1 and 2), two new eudesmane-type sesquiterpenoids, aquisinenoids C and D (3 and 4), one new cucurbitacin, aquisinenoid E (5), and five known cucurbitacins (6–10) were isolated from agarwood of Aquilaria sinensis. The structures of these new compounds, including their absolute configurations, were characterized by spectroscopic and computational methods. The biological evaluation showed that compounds 3 and 9 had an anti-cancer effect on most of the cancer cells at 5 μM, especially in human breast cancer cells. Interestingly, the new compound 3 exhibited more sensitivity on cancer cells than normal cells, highlighting its potential as a novel anti-cancer agent. Mechanically, compound 3 treatment increased the ROS generation and triggered apoptosis of human breast cancer cells. Full article

Retusone A (1), a new sesquiterpene dimer consisting of two guaiane-type sesquiterpenoids, and oleodaphnal (2) were isolated from heartwood of Wikstroemia retusa (Thymelaeaceae). The planar structure of 1 was elucidated on the basis of HRESIMS and NMR spectroscopic data, and the relative stereochemistry was established by X-ray diffraction analysis. The absolute configuration of 1 was determined by electronic circular dichroism. Compound 1 suppressed luciferase reporter gene expression driven by the HBO1 (histone acetyltransferase binding to ORC1) gene promoter in human breast cancer MCF7 cells. Compound 1 also decreased the expression of endogenous HBO1 mRNA and protein, and inhibited proliferation of the cells. These results suggest that retusone A (1), which has a unique dimeric sesquiterpenoid structure with inhibitory activity against HBO1 expression, may contribute to the development of a novel therapeutic candidate for the treatment of breast cancer. Full article

Purpose: Modern, open-source databases provide an unprecedented wealth of information to help drug development. By combining data available in these databases with the proper bioinformatical tools, we can elucidate the molecular targets of natural compounds. One such molecule is curcumol, a guaiane-type sesquiterpenoid hemiketal isolated from Rhizoma Curcumae, which is used for a broad range of diseases in traditional Chinese and Indian medicine. It has been reported to exert anti-tumor activity, but the intrinsic molecular mechanism in hepatocellular carcinoma (HCC) is unclear. Therefore, the present study was designed to reveal the predictive targets and biological mechanisms of curcumol against HCC via a network pharmacology-based approach combined with bioinformatic analytics and to provide proof of concept for further similar investigations. Methods: Data available from open-source databases (Traditional Chinese Medicine Systems Pharmacology, Comparative Toxicogenomic Database, The Cancer Genome Atlas, the Human Protein Atlas project) was processed with the help of a variety of open-source tools (SwissADME, SwissTargetPrediction, JVenn, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, GeneMANIA, Cytoscape). Results: In the present study, the potential of curcumol against HCC was unraveled by network pharmacology-based elucidation. It suggests that curcumol shows exciting druggability with 44 potent homo sapiens biotargets against HCC. The GO terms and KEGG pathways enrichment analyses, curcumol-targets-pathways-HCC network, PPI network, and corresponding in-depth topological analyses, as well as survival analysis, molecular docking simulation indicate that the potential mechanism of curcumol against HCC is complicated, as it may act in various ways, mainly by inducing apoptosis and modulating the inflammatory response, increasing presentation of HCC-specific protein. Conclusion: The present study highlights the potential of curcumol against HCC, giving reference to further experimental study. It also presents a roadmap that can be followed to conduct in silico prescreening of other compounds of interest. Full article

It is a crucial to find target compounds in natural product research. This study presents a concept of structure-guided isolation to find candidate active molecules from herbs. We establish a process of anti-viral sesquiterpene networking. An analysis of the networking suggested that new anti-HBV sesquiterpene may be attributable to eudesmane-, guaiane-, cadinane-, germacane- and bisabolane-type sesquiterpenes. In order to evaluate the efficiency of the structure-based molecular networking, ethanol extract of Saussurea lappa (Decne.) C.B Clarke was investigated, which led to the isolation of two guaiane-type (1 and 14), ten eudesmane-type (2–5 and 8–13), two chain (6 and 7) and one germacrane-type (15) sesquiterpenes, including seven new ones, lappaterpenes A–G (1–7), which are reported on herein. The absolute configurations of the new compounds were established by coupling constants, calculated ECD and ROESY correlations, as well as comparisons of optical rotation values with those of known compounds. The absolute configuration of compound 2 was further confirmed by X-ray diffraction. Compounds 1–15 were evaluated for their potency against hepatitis B virus. Compounds 4, 6, 7 and 9 showed effect on HBsAg with inhibition ratios of more than 40% at 30 μM concentrations. Compounds 14 and 15 inhibited HBsAg secretion with the values of IC₅₀ 0.73 ± 0.18 and 1.43 ± 0.54 μM, respectively. Structure-based molecular networking inspired the discovery of target compounds. Full article

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with −11.8 kcal/mol energy than control vemurafenib −10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme’s active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era. Full article

Ferula penninervis Regel & Schmalh. is a perennial plant used in Kazakh traditional folk medicine to treat epilepsy, neurosis, rheumatism, gastroduodenal ulcers, dyspepsia, wounds, abscesses or tumors. The aim of this work was to isolate series of sesquiterpene lactones from a crude methanolic root extract and investigate their in vitro cytotoxic potential against androgen-dependent prostate cancer LNCaP and epithelial prostate PNT2 cells, as well as to evaluate their melanin production inhibitory effects in murine melanoma B16F10 cells stimulated with α-melanocyte-stimulating hormone (αMSH). Two new (penninervin P and penninervin Q) and five known (olgin, laferin, olgoferin, oferin and daucoguainolactone F) guaiane-type sesquiterpene lactones were isolated with the use of a simple and fast liquid-liquid chromatography method. Olgin and laferin showed the most promising cytotoxic effects in LNCaP cells (IC₅₀ of 31.03 and 23.26 μg/mL, respectively). Additionally, olgin, laferin, olgoferin, and oferin (10 μg/mL) potently impaired melanin release (40.67–65.48% of αMSH + cells) without influencing the viability of B16F10 cells. In summary, our findings might indicate that guaiane-type sesquiterpene lactones from F. penninervis could be regarded as promising candidates for further research in discovering new therapeutic agents with anti-prostate cancer and skin depigmentation properties. Full article

Anvillea garcinii is a medicinal plant used in the Arab region for intestinal diseases, lung and liver diseases, digestive problems, and as an antidiabetic agent. Repeated chromatographic purifications of A. garcinii leaves led to the isolation of three undescribed guaiane sesquiterpene derivatives, named garcinamines F–H, characterized by the presence of an amino acid unit, along with five known sesquiterpene lactones (garcinamines B–E and 9β-hydroxyparthenolide). The structures of the new compounds were established using spectroscopic (1D and 2D NMR) and spectrometric methods (ESIMS). Garcinamine H possesses a double bond at the Δ^1,10 position, a structural feature rarely reported in guaianolide-type sesquiterpenes. The antiproliferative activity of the isolated sesquiterpenes was screened against three different cancer cell lines, and 9β-hydroxyparthenolide and garcinamines C and D displayed significant effects against lung carcinoma (A549), colon carcinoma (LoVo), and breast carcinoma (MCF7) cell lines. Full article

Recently, cultivated “Qi-Nan” (CQN) agarwood has emerged as a new high-quality agarwood in the agarwood market owing to its similar characteristics, such as high content of resin and richness in two 2-(2-phenylethyl)chromone derivatives, 2-(2-phenylethyl)chromone (59) and 2-[2-(4-methoxyphenyl)ethyl]chromone (60), to the wild harvested “Qi-Nan” (WQN) agarwood. In this study, we compared the chemical constituents and fragrant components of two types of WQN agarwood from A. agallocha Roxb. and A. sinensis, respectively, with CQN agarwood and ordinary agarwood varieties. Additionally, we analyzed different samples of WQN agarwood and CQN agarwood by GC-MS, which revealed several noteworthy differences between WQN and CQN agarwood. The chemical diversity of WQN was greater than that of CQN agarwood. The content of (59) and (60) was higher in CQN agarwood than in WQN agarwood. For the sesquiterpenes, the richness and diversity of sesquiterpenes in WQN agarwood, particularly guaiane and agarofuran sesquiterpenes, were higher than those in CQN. Moreover, guaiane-furans sesquiterpenes were only detected by GC-MS in WQN agarwood of A. sinensis and could be a chemical marker for the WQN agarwood of A. sinensis. In addition, we summarized the odor descriptions of the constituents and established the correlation of scents and chemical constituents in the agarwood. Full article

Guaiane-type sesquiterpene lactones are naturally occurring compounds which have attracted attention due to their array of biological activities. In this study, chlorinated guaianolides 1–8, isolated from plants of the genus Centaurea, were evaluated against the human leukemia cell lines HL-60, U-937, a specific U-937 cell line that overexpresses the anti-apoptotic Bcl-2 protein and the human melanoma cell line SK-MEL-1. This established the relevant structure-growth inhibition relationships. Chlorohyssopifolins A (1), C (3) and D (4) and linichlorin A (6) were the most potent compounds in terms of inducing growth inhibition in the four cell lines. IC₅₀ values were below 10 μM in all cases. Chlorohyssopifolins A (1) and D (4) and linichlorin A (6) were potent apoptotic inducers in human U-937 leukemia cells, as determined by fluorescent microscopy and flow cytometry, and their mechanism of action was associated with cytochrome c release, caspase activation and poly(ADP-ribose)polymerase cleavage. Overall this study shows that guaianolides induce cytotoxicity against human tumor cells and provides important insights into the cell death pathways that are involved. Full article