A Survey of Recently Discovered Naturally Occurring Organohalogen Compounds.

The discovery of naturally occurring organohalogen compounds has increased astronomically in the 55 years since they were first discovered─from fewer than 50 in 1968 to a combined 7,958 described examples in three comprehensive reviews. The present survey, which covers the period 2021-2023, brings the number of known natural organohalogens to approximately 8,400. The organization is according to species origin, and coverage includes marine and terrestrial plants, fungi, bacteria, marine sponges, corals, cyanobacteria, tunicates, and other marine organisms.

Chemical Constituents of a Marine-derived Fungus Fusarium oxysporum F0888 and their Antibacterial Activity.

Five new compounds, including four hydroxyphenylacetic acid derivatives, stachylines H-K (1-4), a derivative of hydroxyphenylethanol (5), as well as seven known compounds were obtained from a marine-derived fungus Fusarium oxysporum F0888 isolated from sediments in the South China Sea. The structures and absolute configurations of new compounds were determined by spectroscopic (IR, NMR, and HR-ESI-MS) analyses, comparison of optical rotations, and the modified Mosher's MTPA ester method. Antimicrobial and anti-inflammatory activities of compounds 1-12 were tested. Unfortunately, all of isolated compounds were inactivity.

Cytotoxic Compounds from Marine Fungi: Sources, Structures, and Bioactivity.

Marine fungi, such as species from the Penicillium and Aspergillus genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been successfully isolated and identified from various marine sources, including sponges, coral, algae, mangroves, sediment, and seawater. The cytotoxic compounds derived from marine fungi can be categorized into five distinct classes: polyketides, peptides, terpenoids and sterols, hybrids, and other miscellaneous compounds. Notably, the pre-eminent group among these compounds comprises polyketides, accounting for 307 out of 642 identified compounds. Particularly, within this collection, 23 out of the 642 compounds exhibit remarkable cytotoxic potency, with IC50 values measured at the nanomolar (nM) or nanogram per milliliter (ng/mL) levels. This review elucidates the originating fungal strains, the sources of isolation, chemical structures, and the noteworthy antitumor activity of the 642 novel natural products isolated from marine fungi. The scope of this review encompasses the period from 1991 to 2023.

Meirols A-C: Bioactive Catecholic Compounds from the Marine-Derived Fungus Meira sp. 1210CH-42.

Three new catecholic compounds, named meirols A-C (2-4), and one known analog, argovin (1), were isolated from the marine-derived fungus Meira sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data. Their absolute configurations were elucidated based on ECD calculations. All the compounds exhibited strong antioxidant capabilities with EC50 values ranging from 6.01 to 7.47 µM (ascorbic acid, EC50 = 7.81 µM), as demonstrated by DPPH radical scavenging activity assays. In the α-glucosidase inhibition assay, 1 and 2 showed potent in vitro inhibitory activity with IC50 values of 184.50 and 199.70 µM, respectively (acarbose, IC50 = 301.93 µM). Although none of the isolated compounds exhibited cytotoxicity against one normal and six solid cancer cell lines, 1 exhibited moderate cytotoxicity against the NALM6 and RPMI-8402 blood cancer cell lines with GI50 values of 9.48 and 21.00 µM, respectively. Compound 2 also demonstrated weak cytotoxicity against the NALM6 blood cancer cell line with a GI50 value of 29.40 µM.

Targeted isolation of sorbicilinoids from a deep-sea derived fungus with anti-neuroinflammatory activities.

A chemical fingerprinting approach utilizing LC-MS/MS coupled with 2D NMR data was established to characterize the profile of sorbicilinoid-type metabolites from a deep-sea derived fungus Penicillium rubens F54. Targeted isolation of the cultured fungus resulted in the discovery of 11 undescribed sorbicilinoids namely sorbicillinolides A-K (1-11). Their structures were identified by extensive analyses of the spectroscopic data, including the calculation of electronic circular dichroism and optical rotation for configurational assignments. The cyclopentenone core of sorbicillinolides A-D is likely derived from sorbicillin/dihydrosorbicillin through a newly oxidative rearrangement. The stereoisomers of sorbicillinolides E-G incorporate a nitrogen unit, forming a unique hydroquinoline nucleus. Sorbicillinolides A and C exhibited significant anti-neuroinflammation in LPS-stimulated BV-2 macrophages, achieved by potent inhibition of NO and PGE2 production through the interruption of RNA transcription of iNOS, COX-2 and IL6 in the NF-κB signaling pathway. Further investigation identified COX-2 as a potential target of sorbicillinolide A. These findings suggest sorbicillinolide A as a potential lead for the development of a non-steroidal anti-neuroinflammatory agent.

ß-Glucans obtained from fungus for wound healing: A review.

The cell surface of fungus contains a large number of ß-glucans, which exhibit various biological activities such as immunomodulatory, anti-inflammatory, and antioxidation. Fungal ß-glucans with highly branched structure show great potential as wound healing reagents, because they can stimulate the expression of many immune- and inflammatory-related factors beneficial to wound healing. Recently, the wound healing ability of many fungal ß-glucans have been investigated in animals and clinical trials. Studies have proved that fungal ß-glucans can promote fibroblasts proliferation, collagen deposition, angiogenesis, and macrophage infiltration during the wound healing process. However, the development of fungal ß-glucans as wound healing reagents is not systematically reviewed till now. This review discusses the wound healing studies of ß-glucans obtained from different fungal species. The structure characteristics, extraction methods, and biological functions of fungal ß-glucans with wound healing ability are summarized. Researches about fungal ß-glucan-containing biomaterials and structurally modified ß-glucans for wound healing are also involved.

Structural diversity of microbial secondary metabolites based on chemical epigenetic manipulation.

Fungi are microorganisms with biosynthetic potential that are capable of producing a wide range of chemically diverse and biologically interesting small molecules. Chemical epigenetic manipulation has been increasingly explored as a simple and powerful tool to induce the production of additional microbial secondary metabolites in fungi. This review focuses on chemical epigenetic manipulation in fungi and summarizes 379 epigenetic manipulation products discovered from 2008 to 2022 to promote the discovery of their medicinal value.

Cytotoxic pyrone derivatives from the deep-sea-derived fungus Cladosporium halotolerans FS702.

Two new compounds (R)-6-((8S)-hydroxypropyl)-2-methyl-5,6-dihydro-4H-pyran-4-one (1) and (R)-6-((8R)-hydroxypropyl)-2-methyl-5,6-dihydro-4H-pyran-4-one (2), together with four known compounds were isolated from the marine-derived fungus Cladosporium halotolerans FS702. The structures of these compounds were determined on the basis of extensive spectroscopic analysis including 1D/2D NMR, IR, UV, HRESIMS, ECD calculations as well as the modified Mosher's method. Cytotoxic assay results showed that compound 2 had significant cytotoxic activity against SF-268, MCF-7, HepG-2, and A549 cells lines with IC50 values of 0.16, 0.47, 0.33 and 0.23 µM, respectively.

Exploring colorant production by amazonian filamentous fungi: Stability and applications.

The aim of this study was to investigate the production, stability and applicability of colorants produced by filamentous fungi isolated from soil samples from the Amazon. Initially, the isolates were evaluated in a screening for the production of colorants. The influences of cultivation and nutritional conditions on the production of colorants by fungal isolates were investigated. The colorants produced by selected fungal isolates were chemically characterized using the Liquid Chromatography-Mass Spectrometry technique. The antimicrobial and cytotoxic activities, stability evaluation and applicability of the colorants were investigated. As results, we observed that the isolates Penicillium sclerotiorum P3SO224, Clonostachys rosea P2SO329 and Penicillium gravinicasei P3SO332 stood out since they produced the most intense colorants. Compounds produced by Penicillium sclerotiorum P3SO224 and Clonostachys rosea P2SO329 were identified as sclerotiorin and penicillic acid. The colorant fraction (EtOAc) produced by these species has antimicrobial activity, stability at temperature and at different pHs, stability when exposure to light and UV, and when exposed to different concentrations of salts, as well as being nontoxic and having the ability to dye fabrics and be used as a pigment in creams and soap. Considering the results found in this study, it was concluded that fungi from the soil in the Amazon have the potential to produce colorants with applications in the textile and pharmaceutical industries.

Aspertaichamide a, a novel cytotoxic prenylated indole alkaloid possessing a bicyclo[2.2.2]diazaoctane framework from a marine algal-derived endophytic fungus aspergillus taichungensis 299.

Filamentous fungi belonging to the genus Aspergillus are prodigious producers of alkaloids, particularly prenylated indole alkaloids, that often exhibit structurally diversified skeletons and potent biological activities. In this study, five prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane core ring system, including a novel derivative, namely aspertaichamide A (1), as well as four known compounds, (+)-stephacidin A (2), sclerotiamide (3), (-)-versicolamide B (4), and (+)-versicolamide B (5), were isolated and identified from A. taichungensis 299, an endophytic fungus obtained from the marine red alga Gelidium amansii. The chemical structures of the compounds were elucidated by comprehensive NMR and HRESIMS spectroscopic analyses. In addition to the previously reported prenylated indole alkaloids, aspertaichamide A (1) was characterized as having an unusual ring structure with the fusion of a 3-pyrrolidone dimethylbenzopyran to the bicyclo[2.2.2]diazaoctane moiety, which was rare in these kinds of compounds. The absolute configuration of 1 was determined by TDDFT-ECD calculations. In vitro cytotoxic assays revealed that the novel compound 1 possessed selective cytotoxic activity against five human tumor cell lines (A549, HeLa, HepG2, HCT-116, and AGS), with IC50 values of 1.7-48.5 µM. Most importantly, compound 1 decreased the viability of AGS cells in a concentration-dependent manner with an IC50 value of 1.7 µM. Further studies indicated that 1 may induce AGS cells programmed cell death via the apoptotic pathway.

Tapping into Tapajos: antibacterial potential of fungal strains isolated from decaying wood in the Brazilian Amazon.

The emergence of bacterial resistance to antimicrobials poses a significant health threat. To address this issue, exploring the fungal diversity in freshwater environments in the Amazon Forest has potential in the search for new antimicrobials. This study aimed to investigate the production of antibacterial metabolites by aquatic fungi from Amazon lakes, specifically Lake Juá and Lake Maicá (Brazil-PA). The fungal isolates were obtained from wood fragments submerged in these lakes, and the ethyl acetate extracts were evaluated for antibacterial activity against Staphylococcus aureus ATCC 25923, S. aureus (MRSA), ATCC 43300, Escherichia coli ATCC 25922, and E. coli (ESBL) NCTC 13353. Additionally, toxicity of the extracts (EtOAc with antimicrobial activity) against human fibroblasts MRC-5 was investigated. The study identified 40 fungal strains with antimicrobial screening, and the ethyl acetate extracts of Fluviatispora C34, Helicascus C18, Monodictys C15, and Fusarium solani LM6281 exhibited antibacterial activity. F. solani LM6281 showed the lowest minimum inhibitory concentration (MIC) of 50 µg/mL against S. aureus strains and MIC of 100 µg/mL against E. coli strains including ESBL. The cytotoxicity (IC50) of the extract (EtOAc) of F. solani LM6281 was 34.5 µg/mL. Preliminary studies of the TLC culture and RNM-H from the extract (EtOAc) of F. solani suggested the presence of substances from the class of terpenes, quinones, phenolics, and flavonoids. This study highlights the potential of submerged wood fungi in the Amazon region to produce antibacterial substances, thus identifying them as sources of novel bioactive compounds with potential use in the pharmaceutical industry and regional bioeconomy.

Biogenic synthesis of novel nanomaterials and their applications.

Despite the many benefits derived from the unique features and practicality of nanoparticles, the release of their toxic by-products or products from the synthesis stage into the environment could negatively impact natural resources and organisms. The physical and chemical methods for nanoparticle synthesis involve high energy consumption and the use of hazardous chemicals, respectively, going against the principles of green chemistry. Biological methods of synthesis that rely on extracts from a broad range of natural plants, and microorganisms, such as fungi, bacteria, algae, and yeast, have emerged as viable alternatives to the physical and chemical methods. Nanoparticles synthesized through biogenic pathways are particularly useful for biological applications that have high concerns about contamination. Herein, we review the physical and chemical methods of nanoparticle synthesis and present a detailed overview of the biogenic methods used for the synthesis of different nanoparticles. The major points discussed in this study are the following: (1) the fundamentals of the physical and chemical methods of nanoparticle syntheses, (2) the use of different biological precursors (microorganisms and plant extracts) to synthesize gold, silver, selenium, iron, and other metal nanoparticles, and (3) the applications of biogenic nanoparticles in diverse fields of study, including the environment, health, material science, and analytical chemistry.

Peptides from Marine-Derived Fungi: Chemistry and Biological Activities.

Marine natural products are well-recognized as potential resources to fill the pipeline of drug leads to enter the pharmaceutical industry. In this circumstance, marine-derived fungi are one of the unique sources of bioactive secondary metabolites due to their capacity to produce diverse polyketides and peptides with unique structures and diverse biological activities. The present review covers the peptides from marine-derived fungi reported from the literature published from January 1991 to June 2023, and various scientific databases, including Elsevier, ACS publications, Taylor and Francis, Wiley Online Library, MDPI, Springer, Thieme, Bentham, ProQuest, and the Marine Pharmacology website, are used for a literature search. This review focuses on chemical characteristics, sources, and biological and pharmacological activities of 366 marine fungal peptides belonging to various classes, such as linear, cyclic, and depsipeptides. Among 30 marine-derived fungal genera, isolated from marine macro-organisms such as marine algae, sponges, coral, and mangrove plants, as well as deep sea sediments, species of Aspergillus were found to produce the highest number of peptides (174 peptides), followed by Penicillium (23 peptides), Acremonium (22 peptides), Eurotium (18 peptides), Trichoderma (18 peptides), Simplicillium (17 peptides), and Beauveria (12 peptides). The cytotoxic activity against a broad spectrum of human cancer cell lines was the predominant biological activity of the reported marine peptides (32%), whereas antibacterial, antifungal, antiviral, anti-inflammatory, and various enzyme inhibition activities ranged from 7% to 20%. In the first part of this review, the chemistry of marine peptides is discussed and followed by their biological activity.

New Fusarin Derivatives from the Marine Algicolous Fungus Penicillium steckii SCSIO41040.

Five new fusarin derivatives, steckfusarins A-E (1-5), and two known natural products (6, 7), were isolated and identified from the marine algicolous fungus Penicillium steckii SCSIO 41040. The new compounds, including absolute configurations, were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). All new compounds were evaluated for their antioxidant, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, antioxidant, cholesterol-lowering, acetyl cholinesterase (AChE) enzyme and 6-phosphofructo-2-kinase (PFKFB3) and phosphatidylinositol-3-kinase (PI3K) inhibitory activities. The biological evaluation results revealed that compound 1 exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH), with an IC50 value of 74.5 µg/mL. In addition, compound 1 also showed weak anti-inflammatory activity at a concentration of 20 µM.

Cytotoxic Epipolythiodioxopiperazines from the Deep-Sea-Derived Fungus Exophiala mesophila MCCC 3A00939.

Four new aranotin-type epipolythiodioxopiperazines, graphiumins K-N (1-4), along with four known analogues (5-8), were isolated from the deep-sea-derived fungus Exophiala mesophila MCCC 3A00939. Their structures were elucidated by detailed interpretation of NMR and mass spectrometric data. The absolute configuration of the isolates was deduced by a single-crystal X-ray diffraction analysis and the comparisons of experimental electronic circular dichroism (ECD) data with calculated ECD spectra. Graphiumins K (1) and L (2) exhibited cytotoxic activities against the K562, H69AR, and MDA-MB-231 cancer cells with IC50 values ranging from 2.3 to 5.9 µM.

Antimicrobial, antioxidant, and cytotoxic properties of endophytic fungi isolated from Thysanolaena maxima Roxb., Dracaena spicata Roxb. and Aglaonema hookerianum Schott.

BACKGROUND: Endophytic fungi have recently been recognized as an impressive source of natural biomolecules. The primary objective of the research was to isolate fungal endophytes from Thysanolaena maxima Roxb., Dracaena spicata Roxb. and Aglaonema hookerianum Schott. of Bangladesh and assess their pharmacological potentialities focusing on antimicrobial, antioxidant, and cytotoxic properties. METHODS: The fungal isolates were identified up to the genus level by analyzing their macroscopic and microscopic characteristics. Ethyl acetate extracts of all the fungal isolates were screened for different bioactivities, including antimicrobial (disc diffusion method), antioxidant (DPPH scavenging assay), and cytotoxic (brine shrimp lethality bioassay) activities. RESULTS: Among the thirteen isolates, Fusarium sp. was the most recognized genus, while the others belonged to Colletotrichum sp. and Pestalotia sp. Comparing the bioactivity of all the extracts, Fusarium sp. was shown to be the most effective endophyte, followed by Colletotrichum sp. and Pestalotia sp. In the antimicrobial study, two isolates of Fusarium sp. (internal strain nos. DSLE-1 and AHPE-4) showed inhibitory activity against all the tested bacteria and the highest zone of inhibition (15.5 ± 0.4 mm) was exerted by AHPE-4 against Bacillus subtillis. All the fungal isolates produced mild to moderate free radical scavenging activity, where the highest antioxidant activity was revealed by one isolate of Fusarium sp. (internal strain no. AHPE-3) with an IC50 value of 84.94 ± 0.41 µg/mL. The majority of Fusarium sp. isolates exhibited notable cytotoxic activity, where AHPE-4 exhibited the highest cytotoxicity, having the LC50 value of 14.33 ± 4.5 µg/mL. CONCLUSION: The findings of the study endorsed that the fungal endophytes isolated from T. maxima, D. spicata, and A. hookerianum hold potential as valuable origins of bioactive substances. Nevertheless, more comprehensive research is warranted, which could develop novel natural compounds from these endophytes to treat various infectious and cancerous diseases.

A Pair of Undescribed Alkaloid Enantiomers from Marine Sponge-Derived Fungus Hamigera avellanea and Their Antimicrobial and Cytotoxic Activities.

From marine sponge-associated fungus Hamigera avellanea, thirteen secondary metabolites including a pair of undescribed alkaloid enantiomers (+)-hamiavemin A (4S) (+)-1 and (-)-hamiavemin A (4R) (-)-1. Compound 1 was enantiomers resolved by the Chiralpak AS-3 column, using a hexane/isopropanol mobile phase. Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configuration of (+)-1 and (-)-1 were assigned tentatively by ECD calculations. Among the isolates, compound 6 showed strongest antibacterial activity against Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus, Escherichia coli, Salmonella enterica, and Candida albicans with the MIC values of 2, 2, 16, 32, 64, and 16 µg/mL, respectively, which were stronger than that of the positive control compound, kanamycin (MIC values ranging from 4 to 128 µg/mL). In addition, compounds 1, 2, and 9 showed moderate cytotoxic activity against three cancer cell lines, HepG2, A549, and MCF-7 with the IC50 values ranging from 55.35±1.70 to 83.02±2.85 µg/mL.

( ±)-Dibrevianamides Q1 and Q2, the key precursors of asperginulin A from a marine-derived fungus.

Two pairs of new dimeric diketopiperazine alkaloids, ( ±)-dibrevianamides Q1 and Q2 (( ±)-1 and ( ±)-2), together with seven previously reported analogues (( ±)-3, 4-6, and ( ±)-7) were obtained from a marine-derived fungus Aspergillus sp. The structures of ( ±)-1 and ( ±)-2 were clarified using comprehensive spectroscopic analyses, the calculated ECD, and DP4 + probability methods. Speculated from the biogenesis, ( ±)-dibrevianamides Q1 and Q2 (( ±)-1 and ( ±)-2) might be the key precursor of [2 + 2] diketopiperazine dimers (( ±)-3). Compounds ( +)-1 and ( -)-2 displayed anti-H1N1 virus activity with IC50 values of 12.6 and 19.5 µM. Compound ( +)-1 showed significant activity against Mycobacterium tuberculosis (MIC, 10.2 µg/mL). KEY POINTS: • Two pairs of new dimeric diketopiperazine alkaloids were obtained from the marine-derived fungus Aspergillus sp. • The structures of the new compounds were clarified using comprehensive spectroscopic analyses, the calculated ECD, and DP4 + probability methods. • ( ±)-Dibrevianamides Q1 and Q2 were speculated to be the key precursor of [2 + 2] diketopiperazine dimers ( ±)-asperginulin A.

Fascinating Furanosteroids and Their Pharmacological Profile.

This review article delves into the realm of furanosteroids and related isoprenoid lipids derived from diverse terrestrial and marine sources, exploring their wide array of biological activities and potential pharmacological applications. Fungi, fungal endophytes, plants, and various marine organisms, including sponges, corals, molluscs, and other invertebrates, have proven to be abundant reservoirs of these compounds. The biological activities exhibited by furanosteroids and related lipids encompass anticancer, cytotoxic effects against various cancer cell lines, antiviral, and antifungal effects. Notably, the discovery of exceptional compounds such as nakiterpiosin, malabaricol, dysideasterols, and cortistatins has revealed their potent anti-tuberculosis, antibacterial, and anti-hepatitis C attributes. These compounds also exhibit activity in inhibiting protein kinase C, phospholipase A2, and eliciting cytotoxicity against cancer cells. This comprehensive study emphasizes the significance of furanosteroids and related lipids as valuable natural products with promising therapeutic potential. The remarkable biodiversity found in both terrestrial and marine ecosystems offers an extensive resource for unearthing novel biologically active compounds, paving the way for future drug development and advancements in biomedical research. This review presents a compilation of data obtained from various studies conducted by different authors who employed the PASS software 9.1 to evaluate the biological activity of natural furanosteroids and compounds closely related to them. The utilization of the PASS software in this context offers valuable advantages, such as screening large chemical libraries, identifying compounds for subsequent experimental investigations, and gaining insights into potential biological activities based on their structural features. Nevertheless, it is crucial to emphasize that experimental validation remains indispensable for confirming the predicted activities.

Characteristics and potential clinical applications of the extracellular vesicles of human pathogenic Fungi.

Extracellular vesicles (EVs) are a heterogeneous group of lipid membrane-enclosed compartments that contain different biomolecules and are released by almost all living cells, including fungal genera. Fungal EVs contain multiple bioactive components that perform various biological functions, such as stimulation of the host immune system, transport of virulence factors, induction of biofilm formation, and mediation of host-pathogen interactions. In this review, we summarize the current knowledge on EVs of human pathogenic fungi, mainly focusing on their biogenesis, composition, and biological effects. We also discuss the potential markers and therapeutic applications of fungal EVs.