Search Results (134)

The tetrahydro-β-carboline heterocycle is a privileged scaffold found in numerous natural products and bioactive drugs, demonstrating significant potential for cancer therapy. In this study, we designed and synthesized 33 novel tetrahydro-β-carboline derivatives (2–34) based on this core structure and evaluated their anticancer activity against human lung cancer (A549). Among them, compounds 8 and 16 exhibited potent cytotoxicity against A549 cells, effectively suppressing cell migration and colony formation. Mechanistic studies revealed that these compounds promoted apoptosis by upregulating pro-apoptotic Bax, downregulating anti-apoptotic Bcl-2, and activating caspase proteins. Molecular docking and dynamics simulations demonstrated that compounds 8 and 16 form stable complexes with the Eg5 protein through multiple hydrogen bonds, which was further validated by thermal shift assays. Collectively, these findings indicate that compounds 8 and 16 induce apoptosis in A549 cells by selectively targeting and stabilizing Eg5, highlighting their potential as lead candidates for lung cancer therapy. Full article

Beta-carboline alkaloids (βC-alkaloids) are natural toxins found in various foods, and can also form during the thermal processing of protein-rich ingredients. This study investigated the formation of six βC-alkaloids in pork belly, beef sirloin, mackerel, and cutlassfish subjected to pan-frying, boiling, steaming, and air-frying at 170–250 °C for 2–24 min. Microwave pretreatment (1–5 min) was applied prior to cooking to assess its mitigation potential. Quantification was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Pan-frying significantly promoted βC-alkaloid formation, with harman and norharman levels reaching up to 534.63 µg/kg and 217.06 µg/kg in beef sirloin, and 212.44 µg/kg and 533.01 µg/kg in cutlassfish, respectively. Air-frying generated lower alkaloid levels overall compared to pan-frying. Microwave pretreatment effectively mitigated alkaloid formation. The pretreatment of beef sirloin for 2 min resulted in a reduction in the norharman and harmaline levels by 78.4% and 96.5%, respectively. This study provides a comprehensive comparison of six βC-alkaloids across various food types and cooking methods, demonstrating the influence of cooking parameters on alkaloid formation. This study underscores the importance of understanding the thermal formation of natural toxins in foods and offers insight into practical strategies to minimize their occurrence in daily diets. Full article

Cyvirus cyprinidallo3, also known as Cyprinid herpesvirus 3 (CyHV-3), is a common pathogen of koi and common carp (Cyprinus carpio). Infection of CyHV-3 can lead to high mortality in fry under 4 months of age. CyHV-3 can become latent in recovered fish, and latent CyHV-3 can reactivate under stress conditions and spread the virus. Reactivation of CyHV-3 can also lead to mortality and diseases in latently infected fish. No effective drugs are available to prevent CyHV-3 infection or reactivation from latency. There is a need for the discovery of anti-CyHV-3 drugs. Harmine (HAR) and harmaline (HAL) are β-carboline alkaloids found in the medicinal plant Peganum harmala with antiviral activities against many viruses, including HSV. Here, HAL was evaluated against CyHV-3 infection in vitro and in vivo, respectively. Immediately after a one-hour infection exposure of ~1000 FPU/plate or ~500 PFU/plate, cells treated with 5 µM HAL for 2 h can block nearly 50% or 90% plaque formation in vitro. Only around 50% inhibition was observed in cells treated with the common anti-herpesvirus drug acyclovir (ACV) at 10 or 20 µM for 2 h following 1 h post-infection of ~500 PFU/plate. Cells treated with 10 µM HAL for 30 min, 60 min, 2 h, and 6 h can reduce 60%, 65%, 85.5%, and 85% CyHV-3 replication in vitro, respectively. HAL at 20 µM is still effective against CyHV-3 DNA replication and virion production when the treatment started at 3 and 5 days post-infection for 1 or 2 h, respectively. HAL under 50 µM has little toxicity to cells treated for 24 h. Immersion treatment with 10 µM HAL for 3–4 h daily within the first 5 days post-infection can increase the survival of fry by 60%. In addition, IM injection of HAL at 20 µM can reduce the rate of CyHV-3 reactivation induced by heat stress in latently infected koi. This study demonstrated that HAL could potentially be used to prevent CyHV-3 infection or reactivation from latency. Full article

This study explores the potential anti-H1N1 Influenza A activity of bioactive compounds extracted from Streptomyces ardesiacus, a marine-derived microorganism known for producing diverse secondary metabolites. Four major compounds—1-acetyl-β-carboline, 1H-indole-3-carbaldehyde, anthranilic acid, and indole-3-carboxylic acid—were isolated and characterized through NMR. Among these, the identified structure of 1-acetyl-β-carboline showed the highest IC₅₀ effect, with a dose of 9.71 μg/mL in anti-influenza assays. Using network pharmacology and molecular docking analyses, the interactions of these compounds with key proteins involved in H1N1 pathogenesis were examined. Protein–protein interaction (PPI) networks and Gene Ontology enrichment analysis revealed CDC25B, PARP1, and PTGS2 as key targets, associating these compounds with pathways related to catalytic activity, inflammation, and cell cycle regulation. The molecular docking results demonstrated that 1-acetyl-β-carboline exhibited binding affinities comparable to Tamiflu, the positive control drug, with LibDock scores of 81.89, 77.49, and 89.21 for CDC25B, PARP1, and PTGS2, respectively, compared to Tamiflu’s scores of 84.34, 86.13, and 91.29. These findings highlight the potential of the active compound 1-acetyl-β-carboline from S. ardesiacus as a novel anti-influenza agent, offering insights into their molecular mechanisms of action. The results support further in vitro and in vivo studies to validate the observed inhibitory mechanisms and therapeutic applications against H1N1 Influenza A. Full article

This publication reports the controlled cultivation of Zanthoxylum chiloperone var. angustifolium Engl. (Rutaceae) in several growth substrates under controlled greenhouse conditions. This plant is well-known for its anti-Chagas (trypanocidal) activity, related to the presence of several β-carboline alkaloids. The metabolomic study of Z. chiloperone seedlings over two years of growth (2018–2020) was performed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOFMS). The canthin-6-one alkaloids, canthin-6-one and 5-methoxy-canthin-6-one, were putatively identified in Z. chiloperone extracts. Finally, in vitro and in silico studies of trypanocidal activity were performed, suggesting that canthin-6-one alkaloids could interact with the main pharmacological targets against Trypanosoma cruzi, cruzain protease, dihydroorotate dehydrogenase, lanosterol 14-alpha-demethylase, farnesyl diphosphate, and squalene synthases. Full article

This article investigated the composition and content of volatile organic compounds (VOCs) in cumin from three Xinjiang origins (Hami, Turpan, and Hetian) at different processing temperatures. VOCs varied with temperature and origin, but alcohols and terpenes were predominant in all samples. Hetian cumin exhibited the highest VOC content and stability under specific treatments, divided into an ambient temperature treatment (AMB) and a 70 °C heat treatment. A cluster analysis revealed high similarity between replicates and significant differences among the samples. A Venn diagram comparison showed that 70 °C processing reduced the number of common VOCs among the three origins from 36 to 19, which is a decrease of 47.22%, indicating a significant impact of heating on cumin VOCs and possibly promoting the formation of new compounds. Finally, utilizing the varying abilities of different types of polyphenols to inhibit heterocyclic aromatic amines (HAAs), six polyphenolic compounds, identified as sesamin, 6-caffeoylsucrose, apigenin, eschweilenol C, kaempferol glucuronide, and luteolin, were preliminarily determined to play an active role in the β-carboline HAA simulation system. Full article

In our previous study, Lentzea sp. JNUCC 0626 was isolated from Hwasun Gotjawal on Jeju Island, and its melanogenic effects were confirmed in B16F10 melanoma cells through the identification of 1-acetyl-β-carboline. In this study, we conducted a comprehensive taxonomic characterization of Lentzea sp. JNUCC 0626, including enzymatic activities, carbohydrate metabolism, growth conditions, and cellular composition. Major fatty acids identified were iso-C16:0, iso-C15:0, and C15:0 anteiso, with polar lipids such as diphosphatidylglycerol, phosphatidylethanolamine, and several unidentified lipids. Ubiquinone Q-9 was determined as the predominant respiratory quinone. Enzymatic activity analysis (API ZYM) showed alkaline phosphatase, esterase (C4), esterase lipase (C8), and leucine arylamidase activities, while carbohydrate metabolism analysis (API 50CHB) indicated acid production from esculin alone. Complete genome sequencing revealed a 10,602,950 bp linear chromosome and a 177,940 bp plasmid. This plasmid encodes essential plasmid-related genes, including a Type IV secretion system and ParA proteins critical for plasmid transfer and stability. These findings suggest that the plasmid in Lentzea sp. JNUCC 0626 could be utilized for developing host–vector systems to facilitate the combinatorial biosynthesis of novel bioactive compounds. Comparative genomic analysis identified Lentzea pudingi CGMCC 4.7319 as the closest relative, but significant genetic divergence (dDDH 46.7%, ANI 88.02%) strongly supports the classification of Lentzea sp. JNUCC 0626 as a novel species. AntiSMASH analysis revealed 34 biosynthetic gene clusters (BGCs), highlighting the strain’s capacity to produce diverse bioactive compounds. Finally, the JNUCC 0626 extract exhibited concentration-dependent NO inhibition in LPS-stimulated RAW 264.7 cells, demonstrating significant anti-inflammatory activity. This suggests that the secondary metabolites inferred from genomic analysis may contribute to these observed bioactivities. Full article

In this study, we aimed to investigate the inhibitory effects of cumin and cumin extracts from different origins (Hami, Turpan, and Hetian) on the formation of β-carboline heterocyclic amines (HCAs) in smoked meat and simulated systems, and to assess their potential as natural inhibitors in the food industry. The novelty of our research lies in the comprehensive comparative analysis of cumin extracts from different origins, which has not been fully explored in previous studies. We first conducted a quantitative analysis of the total phenol and flavonoid content in cumin extracts from the three origins and evaluated their antioxidant capacities. Subsequently, through simulation experiments, we assessed the inhibitory effects of these extracts on the formation of β-carboline heterocyclic amines and determined their free radical scavenging abilities. To further validate the practical application potential of these extracts, we prepared meat patty samples containing different concentrations of cumin powder, simulating actual processing conditions. The experimental results showed that while the total phenol content in cumin extracts from all origins was similar, averaging around 1.56 mg/g, there was a significant difference in the total flavonoid content, with the highest level observed in the Hetian cumin extract at 6.7 mg/g. Additionally, the Hetian cumin extract demonstrated superior antioxidant capacity, with an FRAP antioxidant activity reaching 21.04 μM TE/g dw, the highest among all samples. Our study also found that the inhibitory effect of cumin extracts on HCA formation was closely related to their free radical scavenging ability, with the Hetian cumin extract showing the strongest scavenging capacity. The addition of cumin powder to meat patties significantly reduced the content of β-carboline heterocyclic amines, particularly at lower cumin concentrations. In summary, our research results highlight the potential of cumin, especially from Hetian, as a natural inhibitor of β-carboline heterocyclic amine formation in processed meats. This study not only provides the food industry with a potential natural additive to improve food safety and quality, but also offers new directions for future research, namely by comparing natural plant extracts from different origins to explore their potential applications in food processing. Full article

Ulcerative colitis (UC) is an inflammatory disease of the intestinal mucosa, and its incidence is steadily increasing worldwide. As a traditional Chinese medicinal insect, Periplaneta americana has been broadly utilized in clinical practice to treat wound healing. The tryptophan (Trp), tryptamine (Try), and 1,2,3,4-tetrahydrogen-β-carboline-3-carboxylic acid (Thcc) identified from P. americana concentrated ethanol-extract liquid (PACEL) exhibit significant cell proliferation-promoting and anti-inflammatory effects in the treatment of UC, but the mechanism involved remains obscure. Here, a dextran sulfate sodium (DSS)-induced UC mouse model was used to investigate the efficacy of high/low doses of PACEL, Trp, Try, and Thcc. Transcriptome sequencing was employed to detect the gene expression in the mouse intestine. The results showed that high doses of PACEL, Trp, Try, and Thcc could significantly improve weight loss and diarrhea, notably in the PACEL and Trp groups. Transcriptome analysis indicated that statistically changed genes in four treatment groups were specifically enriched in the immune system. Of these, the integrated analysis identified six hub genes (IL1β, CCL4, CXCL5, CXCR2, LCN2, and MMP9) regulated by NF-κB, which were significantly downregulated. This study investigates the molecular mechanisms underlying the UC treatment properties of indole analogues from PACEL, potentially through the inhibition of the NF-κB signaling pathway. Full article

As the resistance of Plasmodium to the existing antimalarials increases, there is a crucial need to expand the antimalarial drug pipeline. We recently identified potent antimalarial compounds, namely harmiquins, hybrids derived from the β-carboline alkaloid harmine and 4-amino-7-chloroquinoline, a key structural motif of chloroquine (CQ). To further explore the structure−activity relationship, we synthesised 13 novel hybrid compounds at the position N-9 of the β-carboline ring and evaluated their efficacy in vitro against Plasmodium falciparum 3D7 and Dd2 strains (CQ sensitive and multi-drug resistant, respectively). All compounds exhibit persistent antimalarial activity against both strains of P. falciparum. The most interesting derivatives had low nanomolar activity against both strains (IC₅₀ (33) = 4.7 ± 1.3 nM against Pf3D7 and 6.5 ± 2.5 nM against PfDd2; IC₅₀ (37) = 4.6 ± 0.6 nM against 3D7 and 10.5 ± 0.4 nM against Dd2). Resistance indices (RIs) ranged from 0.9 to 5.3 compared to CQ (RI = 14.4), highlighting their superior consistency in activity against both strains. The cytotoxicity screening performed on HepG2 revealed over 3 orders of magnitude higher IC₅₀ for most of the compounds, with SIs from 711.0 to 8081.8. Spectroscopic studies explored the affinities of newly synthesised compounds for DNA, RNA, and HSA. Both tested hybrids, 34 and 39, were intrinsically fluorescent in an aqueous medium, characterised by remarkable Stokes shifts of emission maxima (Δλ = +103 and +93 nm for 34 and 39, respectively). Fluorimetric experiments revealed that compound 34, with its shorter and more flexible linker, exhibited at least an order of magnitude higher affinity toward ds-DNAs versus ds-RNA and two orders of magnitude higher affinity toward GC-DNAs compared to 39. The behaviour of the investigated compounds upon binding to HSA is very similar, showing a strong hypsochromic shift of the emission maximum (almost Δλ = −70 nm) and demonstrating their effectiveness as fluorimetric probes for distinguishing between DNA/RNA and proteins. Full article

A comprehensive phytochemical investigation of the twigs/leaves and flower buds of Kolkwitzia amabilis, a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (1–4 and 7–13), 20 triterpenoids (5, 6, and 14–31), and 8 phenylpropanoids (32–39). Among these, amabiliosides A (1) and B (2) represent previously undescribed bis-iridoid glycosides, while amabiliosides C (3) and D (4) feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro-β-carboline-5-carboxylic acid moiety. Amabiliacids A (5) and B (6) are 24-nor-ursane-type triterpenoids characterized by an uncommon ∆^11,13(18) transannular double bond. Their chemical structures and absolute configurations were elucidated through spectroscopic data and electronic circular dichroism analyses. Compound 2 exhibited a moderate inhibitory effect against acetyl CoA carboxylase 1 (ACC1), with an IC₅₀ value of 9.6 μM. Lonicejaposide C (8), 3β-O-trans-caffeoyl-olean-12-en-28-oic acid (29), and (23E)-coumaroylhederagenin (31) showed notable inhibitory effects on ATP-citrate lyase (ACL), with IC₅₀ values of 3.6, 1.6, and 4.7 μM, respectively. Additionally, 3β-acetyl-ursolic acid (17) demonstrated dual inhibitory activity against both ACC1 and ACL, with IC₅₀ values of 10.3 and 2.0 μM, respectively. The interactions of the active compounds with ACC1 and ACL enzymes were examined through molecular docking studies. From a chemotaxonomic perspective, the isolation of bis-iridoid glycosides in this study may aid in clarifying the taxonomic relationship between the genera Kolkwitzia and Lonicera within the Caprifoliaceae family. These findings highlight the importance of conserving plant species with unique and diverse secondary metabolites, which could serve as potential sources of new therapeutic agents for treating ACC1/ACL-associated diseases. Full article

The present study designed and computationally optimized a series of novel β-carboline derivatives to investigate the interaction between designed ligands and selected proteins. Therefore, to find better intercalating agents, β-carboline was used as a basic skeleton, and a series of novel β-carboline derivatives with various aryl groups at C-1 sites and a benzyl group at N-9 position were designed and synthesized and in silico-evaluated for their anticancer activity. The structures of the compounds were identified by employing a range of spectroscopic techniques, including IR, ¹H NMR, ¹³C NMR, and elemental analyses. The silico docking study was performed to determine the maximum interaction between designed ligands and those with protein 1pye CDK₂ inhibitor. The results of the molecular docking study with enzyme 1PYE indicate that the scores and binding modes are similar to those of the co-crystallized ligand. This similarity confirms the anticancer activity of the studied compound, suggesting its potential as a promising candidate for further development as an anticancer agent. In silico ADME prediction involves using computational methods to assess the absorption, distribution, metabolism, and excretion of compounds, as well as forecasting their drug-like properties. Full article

A series of β-carboline derivatives containing nitrogen heterocycles were designed and synthesized. All compounds were screened for their antitumor activity against four human tumor cell lines (A549, K562, PC-3, T47D). Notably, compound N-(4-(morpholinomethyl)phenyl)-2-((5-(1-(3,4,5-trimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl)-1,3,4-oxadiazol-2-yl)thio)acetamide (8q) exhibited significant inhibitory activity against PC-3 cells with an IC₅₀ value of 9.86 µM. Importantly, compound 8q effectively suppressed both the proliferation and migration of PC-3 cells. Mechanistic studies revealed that compound 8q induced cell apoptosis and caused the accumulation of reactive oxygen species (ROS), leading to cell cycle arrest in the G0/G1 phase in PC-3 cells. Full article

The genus Lentzea is a prolific source of bioactive and structurally diverse secondary metabolites. We isolated a novel strain, Lentzea sp. JNUCC 0626, from Hwasun Gotjawal on Jeju Island, Korea. Based on 16S rRNA partial gene sequence analysis, strain JNUCC 0626 is closely related to Lentzea isolaginshaensis NX62 (99.41% similarity), Lentzea pudingi DHS C021 (99.31%), and Lentzea cavernae SYSU K10001 (99.26%). From the fermentation broth of JNUCC 0626, we isolated 1-acetyl-β-carboline, whose structure was established using IR, HR-ESI-MS, and 1D- and 2D-NMR techniques. 1-acetyl-β-carboline was found to activate melanogenesis in mouse B16F10 cells without cytotoxicity at concentrations up to 50 μM. At this concentration, the compound increased melanin content by 27.44% and tyrosinase activity by 240.64% compared to the control, by upregulating key melanogenic enzymes, including tyrosinase, TRP-1, TRP-2, and microphthalmia-associated transcription factor (MITF), a central regulator of melanogenesis. In addition, 1-acetyl-β-carboline significantly inhibited ERK phosphorylation, reducing it by 20.79% at a concentration of 12.5 μM and by 25.63% at 25 μM. This inhibition supports the hypothesis that 1-acetyl-β-carboline enhances melanin synthesis by upregulating MITF and melanogenic enzymes via the ERK signaling pathway. This study aimed to isolate and identify 1-acetyl-β-carboline from a novel strain of Lentzea sp. JNUCC 0626, discovered in Gotjawal, Jeju Island, and to evaluate its effect on melanin production in B16F10 melanoma cells. Skin irritation tests on 32 subjects confirmed its safety for topical use, and the findings suggest that 1-acetyl-β-carboline, which enhances melanogenesis without cytotoxicity, holds promise as a therapeutic agent for hypopigmentation-related conditions or as a cosmetic ingredient. Full article

The discovery of a lead compound against Candida albicans is urgently needed because of the lack of clinically available antifungal drugs and the increase in drug resistance. Herein, a β-carboline alkaloid methylaervine (MET) exhibited potential activity against C. albicans (MIC = 16–128 μg/mL), no hemolytic toxicity, and a low tendency to induce drug resistance. An antifungal mechanism study indicated that MET effectively inhibited the biofilm formation and disrupted the mature biofilm. Moreover, filamentation formation and spore germination were also weakened. The electron microscopy analysis revealed that MET could damage the cell structure, including the cell wall, membrane, and cytoplasm. In particular, the permeability and integrity of the cell membrane were destroyed. When it entered the fungi cell, it interfered with the redox homeostasis and DNA function. Overall, MET can inhibit the growth of C. albicans from multiple channels, such as biofilm, filamentation, cell structure, and intracellular targets, which are difficult to mutate at the same time to generate drug resistance. This work provides a promising lead compound for the creation of new antifungal agents against C. albicans. Full article