Search Results (36)

A new alkaloid (orychophragvioline A) and nine known compounds were yielded from the seeds of Orychophragmus violaceus. Their structures were determined by various spectroscopic techniques and single-crystal X-ray diffraction. Orychophragvioline A is a rare alkaloid with an unusual 1-methyl-4-phenyl-2,3-diketopiperazine skeleton connected with a guanidine group via an amide bond. The results of antitumor tests in vitro showed that it exhibited prominent cytotoxicity against Hela cells with an IC₅₀ value of 11.95 ± 1.52 μM. Further investigations suggested that it significantly inhibited cellular proliferation, migration, and invasion in a dose-dependent manner, thus inducing the apoptosis of Hela cells. These findings indicate that orychophragvioline A can be regarded as a potential natural leading compound against cervical cancer. Full article

Nitrogen heterocycles have drawn considerable attention because of their structurally novel and significant biological activities. Marine-derived fungi, especially the Aspergillus species, possess unique metabolic pathways to produce secondary metabolites with novel structures and potent biological activities. This review prioritizes the structural diversity and biological activities of nitrogen heterocycles that are produced by marine-derived Aspergillus species from January 2019 to January 2024, and their relevant biological activities. A total of 306 new nitrogen heterocycles, including seven major categories—indole alkaloids, diketopiperazine alkaloids, quinazoline alkaloids, isoquinoline alkaloids pyrrolidine alkaloids, cyclopeptide alkaloids, and other heterocyclic alkaloids—are presented in this review. Among these nitrogen heterocycles, 52 compounds had novel skeleton structures. Remarkably, 103 compounds showed various biological activities, such as cytotoxic, antimicrobial, anti-inflammatory, antifungal, anti-virus, and enzyme-inhibitory activities, and 21 compounds showed potent activities. This paper will guide further investigations into the structural diversity and biological activities of nitrogen heterocycles derived from the Aspergillus species and their potential contributions to the future development of new natural drug products in the medicinal and agricultural fields. Full article

A new prenylated indole diketopiperazine alkaloid, rubrumline P (1), was isolated along with six more analogues and characterized from the fermentation culture of a marine sediment-derived fungus, Aspergillus chevalieri, collected at a depth of 15 m near the lighthouse in Dahab, Red Sea, Egypt. In the current study, a bioassay-guided fractionation allowed for the identification of an active fraction displaying significant cytotoxic activity against the human pancreatic adenocarcinoma cell line PANC-1 from the EtOAc extract of the investigated fungus compared to the standard paclitaxel. The structures of the isolated compounds from the active fraction were established using 1D/2D NMR spectroscopy and mass spectrometry, together with comparisons with the literature. The absolute configuration of the obtained indole diketopiperazines was established based on single-crystal X-ray diffraction analyses of rubrumline I (2) and comparisons of optical rotations and NMR data, as well as on biogenetic considerations. Genome sequencing indicated the formation of prenyltransferases, which was subsequently confirmed by the isolation of mono-, di-, tri-, and tetraprenylated compounds. Compounds rubrumline P (1) and neoechinulin D (4) confirmed preferential cytotoxic activity against PANC-1 cancer cells with IC₅₀ values of 25.8 and 23.4 µM, respectively. Although the underlying mechanism-of-action remains elusive in this study, cell cycle analysis indicated a slight increase in the sub-G1 peak after treatment with compounds 1 and 4. Full article

Eurotium is the teleomorph genus associated with the section Aspergillus. Eurotium comprises approximately 20 species, which are widely distributed in nature and human environments. Eurotium is usually the key microorganism for the fermentation of traditional food, such as Fuzhuan brick tea, Liupao tea, Meju, and Karebushi; thus, Eurotium is an important fungus in the food industry. Eurotium has been extensively studied because it contains a series of interesting, structurally diverse, and biologically important secondary metabolites, including anthraquinones, benzaldehyde derivatives, and indol diketopiperazine alkaloids. These secondary metabolites have shown multiple biological activities, including antioxidative, antimicrobial, cytotoxic, antitumor, insecticidal, antimalarial, and anti-inflammatory activities. This study presents an up-to-date review of the phytochemistry and biological activities of all Eurotium species. This review will provide recent advances on the secondary metabolites and their bioactivities in the genus Eurotium for the first time and serve as a database for future research and drug development from the genus Eurotium. Full article

Alkaloids represent a large family of natural products with diverse structures and bioactivities. These compounds and their derivatives have been widely used in clinics to treat various diseases. The endophytic Aspergillus is a filamentous fungus renowned for its extraordinary ability to produce active natural products of high therapeutic value and economic importance. This review is the first to focus on Aspergillus-derived alkaloids. Through an extensive literature review and data analysis, 263 alkaloids are categorized according to their structural features into those containing cytochalasans, diketopiperazine alkaloids, quinazoline alkaloids, quinoline alkaloids, indole alkaloids, pyrrolidine alkaloids, and others. These metabolites exhibited diverse biological activities, such as antibacterial activity, cytotoxicity, anti-inflammatory activity, and α-glucosidase, ACE, and DPPH inhibitory activities. The bioactivity, structural diversity, and occurrence of these alkaloids are reviewed in detail. Full article

Two new quinazolinone diketopiperazine alkaloids, including versicomide E (2) and cottoquinazoline H (4), together with ten known compounds (1, 3, and 5–12) were isolated and identified from Aspergillus versicolor AS-212, an endozoic fungus associated with the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts. Their chemical structures were determined by an extensive interpretation of the spectroscopic and X-ray crystallographic data as well as specific rotation calculation, ECD calculation, and comparison of their ECD spectra. The absolute configurations of (−)-isoversicomide A (1) and cottoquinazoline A (3) were not assigned in the literature reports and were solved in the present work by single-crystal X-ray diffraction analysis. In the antibacterial assays, compound 3 exhibited antibacterial activity against aquatic pathogenic bacteria Aeromonas hydrophilia with an MIC value of 18.6 μM, while compounds 4 and 8 exhibited inhibitory effects against Vibrio harveyi and V. parahaemolyticus with MIC values ranging from 9.0 to 18.1 μM. Full article

Alkaloids, as one of the largest classes of natural products with diverse structures, are an important source of innovative medicines. Filamentous fungi, especially those derived from the marine environment, are one of the major producers of alkaloids. In this study, three new alkaloids, sclerotioloids A–C (1–3), along with six known analogs (4–9), were obtained under the guidance of the MS/MS-based molecular networking from the marine-derived fungus, Aspergillus sclerotiorum ST0501, collected from the South China Sea. Their chemical structures were elucidated by comprehensive analysis of the spectroscopic data, including 1D and 2D NMR and HRESIMS. Additionally, the configuration of compound 2 was unambiguously determined by X-ray single crystal diffraction, and that of compound 3 was determined by the TDDFT-ECD approach. Sclerotioloid A (1) represents the first example of 2,5-diketopiperazine alkaloid with a rare terminal alkyne. Sclerotioloid B (2) showed the inhibition of NO production induced by lipopolysaccharide (LPS), with an inhibition rate of 28.92% higher than that of dexamethasone (25.87%). These results expanded the library of fungal-derived alkaloids and further prove the potential of marine fungi in the generation of alkaloids with new scaffolds. Full article

A large body of fungal secondary metabolites has been discovered to exhibit potent antibacterial activities with distinctive mechanisms and has the potential to be an untapped resource for drug discovery. Here, we describe the isolation and characterization of five new antibacterial indole diketopiperazine alkaloids, namely 24,25-dihydroxyvariecolorin G (1), 25-hydroxyrubrumazine B (2), 22-chloro-25-hydroxyrubrumazine B (3), 25-hydroxyvariecolorin F (4), and 27-epi-aspechinulin D (5), along with the known analogue neoechinulin B (6) from a fungal strain of deep-sea cold seep-derived Aspergillus chevalieri. Among these compounds, 3 and 4 represented a class of infrequently occurring fungal chlorinated natural products. Compounds 1–6 showed inhibitory activities against several pathogenic bacteria with MIC values ranging from 4 to 32 μg/mL. It was revealed that compound 6 could induce structural damage to the Aeromonas hydrophila cells based on the observation by scanning electron microscopy (SEM), which led to the bacteriolysis and death of A. hydrophila, suggesting that neoechinulin B (6) might be a potential alternative to novel antibiotics development. Full article

Total synthesis of the 2-formylpyrrole alkaloid hemerocallisamine I is presented, both in racemic and enantiopure form. Our synthetic strategy involves (2S,4S)-4-hydroxyglutamic acid lactone as the key intermediate. Starting from an achiral substrate, the target stereogenic centers were introduced by means of crystallization-induced diastereomer transformation (CIDT) in a highly stereoselective fashion. A Maillard-type condensation was crucial to constructing the desired pyrrolic scaffold. Full article

Metabolomics strategies are important tools to get holistic chemical information from a system, but they are scarcely applied to endophytic fungi to understand their chemical profiles of biosynthesized metabolites. Here Penicillium sp. was cultured using One Strain Many Compounds (OSMAC) conditions as a model system to demonstrate how this strategy can help in understanding metabolic profiles and determining bioactive metabolites with the application of metabolomics and statistical analyses, as well as molecular networking. Penicillium sp. was fermented in different culture media and the crude extracts from mycelial biomass (CEm) and broth (CEb) were obtained, evaluated against bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa), and the metabolomic profiles by LC-DAD-MS were obtained and chemometrics statistical analyses were applied. The CEm and CEb extracts presented different chemical profiles and antibacterial activities; the highest activities observed were against S. aureus from CEm (MIC = 16, 64, and 128 µg/mL). The antibacterial properties from the extracts were impacted for culture media from which the strain was fermented. From the Volcano plot analysis, it was possible to determine statistically the most relevant features for the antibacterial activity, which were also confirmed from biplots of PCA as strong features for the bioactive extracts. These compounds included 75 (13-oxoverruculogen isomer), 78 (austalide P acid), 87 (austalide L or W), 88 (helvamide), 92 (viridicatumtoxin A), 96 (austalide P), 101 (dihydroaustalide K), 106 (austalide k), 110 (spirohexaline), and 112 (pre-viridicatumtoxin). Thus, these features included diketopiperazines, meroterpenoids, and polyketides, such as indole alkaloids, austalides, and viridicatumtoxin A, a rare tetracycline. Full article

Marine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide (1) from the marine-derived fungus Penicillium dimorphosporum KMM 4689 associated with a soft coral. The structure of this metabolite, including its absolute configuration, was determined by HR-MS, 1D and 2D NMR as well as CD data. Compound 1 is a very first deoxyisoaustamide alkaloid possessing two double bonds in the proline ring. The isolated compound was noncytotoxic to a panel of human normal and cancer cell lines up to 100 µM. At the same time, compound 1 resensitized prostate cancer 22Rv1 cells to androgen receptor (AR) blocker enzalutamide. The mechanism of this phenomenon was identified as specific drug-induced degradation of androgen receptor transcription variant V7 (AR-V7), which also resulted in general suppression of AR signaling. Our data suggest that the isolated alkaloid is a promising candidate for combinational therapy of castration resistant prostate cancer, including drug-resistant subtypes. Full article

Fungus continues to attract great attention as a promising pool of biometabolites. Aspergillus ochraceus Wilh (Aspergillaceae) has established its capacity to biosynthesize a myriad of metabolites belonging to different chemical classes, such as isocoumarins, pyrazines, sterols, indole alkaloids, diketopiperazines, polyketides, peptides, quinones, polyketides, and sesquiterpenoids, revealing various bioactivities that are antimicrobial, cytotoxic, antiviral, anti-inflammatory, insecticidal, and neuroprotective. Additionally, A. ochraceus produces a variety of enzymes that could have variable industrial and biotechnological applications. From 1965 until June 2022, 165 metabolites were reported from A. ochraceus isolated from different sources. In this review, the formerly separated metabolites from A. ochraceus, including their bioactivities and biosynthesis, in addition, the industrial and biotechnological potential of A. ochraceus are highlighted. Full article

Actinomycetes are natural architects of numerous secondary metabolites including antibiotics. With increased multidrug-resistant (MDR) pathogens, antibiotics that can combat such pathogens are urgently required to improve the health care system globally. The characterization of actinomycetes available in Nepal is still very much untouched which is the reason why this paper showcases the characterization of actinomycetes from Nepal based on their morphology, 16S rRNA gene sequencing, and metabolic profiling. Additionally, antimicrobial assays and liquid chromatography-high resolution mass spectrometry (LC-HRMS) of ethyl acetate extracts were performed. In this study, we employed a computational-based dereplication strategy for annotating molecules which is also time-efficient. Molecular annotation was performed through the GNPS server, the SIRIUS platform, and the available databases to predict the secondary metabolites. The sequencing of the 16S rRNA gene revealed that the isolates BN6 and BN14 are closely related to Streptomyces species. BN14 showed broad-spectrum antibacterial activity with the zone of inhibition up to 30 mm against Staphylococcus aureus (MIC: 0.3051 µg/mL and MBC: 9.7656 µg/mL) and Shigella sonnei (MIC: 0.3051 µg/mL and MBC: 4.882 µg/mL). Likewise, BN14 also displayed significant inhibition to Acinetobacter baumannii, Klebsiella pneumoniae, and Salmonella typhi. GNPS approach suggested that the extracts of BN6 and BN14 consisted of diketopiperazines ((cyclo(D-Trp-L-Pro), cyclo(L-Leu-L-4-hydroxy-Pro), cyclo(L-Phe-D-Pro), cyclo(L-Trp-L-Pro), cyclo(L-Val-L-Pro)), and polypeptide antibiotics (actinomycin D and X2). Additional chemical scaffolds such as bacterial alkaloids (bohemamine, venezueline B, and G), anthramycin-type antibiotics (abbeymycin), lipase inhibitor (ebelactone B), cytocidal (oxopropaline D), antifungal and antitumor antibiotics (reductiomycin, streptimidone, deoxynybomycin), alaremycin, fumaramidmycin, anisomycin, and others were also annotated, which were further confirmed by using the SIRIUS platform, and literature survey. Thus, the bioprospecting of natural products from Streptomyces species from Nepal could be a potential source for the discovery of clinically significant and new antimicrobial agents in the future. Full article

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 M^pro with IC₅₀ value of 0.47 μM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 M^pro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related M^pro inhibitors. Full article

Colorectal cancer is one of the most common cancers diagnosed in the world. Chemotheraphy is one of the most common methods used for the pharmacological treatment of this cancer patients. Nevertheless, the adverse effect of chemotherapy is not optimized for improving the quality of life of people who are older, who are the most vulnerable subpopulation. This review presents recent updates regarding secondary metabolites derived from marine fungi and actinobacteria as novel alternatives for cytotoxic agents against colorectal cancer cell lines HCT116, HT29, HCT15, RKO, Caco-2, and SW480. The observed marine-derived fungi were from the species Aspergillus sp., Penicillium sp., Neosartorya sp., Dichotomomyces sp., Paradendryphiella sp., and Westerdykella sp. Additionally, Streptomyces sp. and Nocardiopsis sp. are actinobacteria discussed in this study. Seventy one compounds reviewed in this study were grouped on the basis of their chemical structures. Indole alkaloids and diketopiperazines made up most compounds with higher potencies when compared with other groups. The potency of indole alkaloids and diketopiperazines was most probably due to halogen-based functional groups and sulfide groups, respectively. Full article