Cytotoxic naphthoquinone and a new succinate ester from the soil fungus Fusarium solani PSU-RSPG227

A new naphthoquinone, solaninaphthoquione (1), and a new succinate ester derivative, 4-(4-hydroxyphenethoxy)-4-oxobutanoic acid (2), were isolated from the soil fungus Fusarium solani PSU-RSPG227 together with five previously reported compounds; javanicin (3), monaspilosin (4), aspergillol B (5), tyrosol (6) and 4-hydroxyphenylacetic acid (7). Their structures were elucidated primarily by NMR spectroscopic data. Due to paucity of materials, compounds 2, 4 and 5 as well as analogues of 5 were prepared for biological activity evaluation. Compound 1 showed significant cytotoxic activity against breast cancer (MCF-7) cells and mild cytotoxic activity against oral human carcinoma (KB) cells (IC₅₀ values of 21.3 and 22.6 μM, respectively) compared to standard compounds. Compound 1 also displayed weak antimalarial activity (IC₅₀ of 26.1 μM).     

Curvularin derivatives from the soil-derived fungus Aspergillus polyporicola PSU-RSPG187

Two new curvularin derivatives, curvulopyran (1) and ent-curvulone A (2), along with ten known compounds including five cytochalasins and five curvularins, were isolated from a culture broth of the soil-derived fungus Aspergillus polyporicola PSU-RSPG187. Their structures were determined by spectroscopic methods. Known aspochalasin D displayed moderate antifungal activity against flucytosine–resistant Cryptococcus neoformans with an MIC value of 32 μg/mL and showed no cytotoxic activity against noncancerous cell lines. In addition, known α,β–dehydrocurvularin exhibited potential cytotoxic activity against both KB and MCF-7 cell lines with the IC₅₀ values of 11.26 and 19.50 μM. Unfortunately, it was strongly active against Vero cell lines.     

Pyranones from kiwi-associated fungus Fusarium tricinctum and their antibacterial activity

Four new pyrone derivatives, fusaritricins A–D (1−4), together with five known analogues, were obtained from the kiwi endophytic fungus Fusarium tricinctum. Their structures were established by extensive spectroscopic data analysis and their absolute configurations were determined by quantum chemical calculations. Compounds 1, 2, 3, and 9 exhibited antibacterial activity against plant pathogen Pseudomonas syringae pv. Actinidiae (Psa) with MIC values of 128, 128, 64, and 64 µg/mL, respectively. This is the first report of anti-Psa activity of pyrone derivatives.     

Trichothecenes from the fungus Acremonium crotocinigenum BCC 20012

Two new trichothecenes (1 and 2) and a new chloroderivative of a trichothecene analogue (3) together with four known trichothecenes, crotocin, trichothecin, 8-deoxytrichothecinol B, and a trichothecene analogue, were isolated from the fungus Acremonium crotocinigenum BCC 20012. The structures of these compounds were elucidated by extensive spectroscopic analysis. Among the tested metabolites, trichothecin itself showed strongest antimalarial activity against Plasmodium falciparum K1, and cytotoxic activity against Vero cell lines with IC₅₀ values of 0.05 and 0.13 μg/mL, respectively.     

Pyrone derivatives from the marine-derived fungus Nigrospora sp. PSU-F18

Pyrones, named nigrosporapyrones A-D (1-4), and five known compounds were isolated from the marine-derived fungus Nigrospora PSU-F18. Their structures were elucidated on the basis of spectroscopic evidence. The antibacterial activity against the standard Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus was evaluated.     

Antimycobacterial dihydronaphthalenone from the endophytic fungus Nodulisporium sp. of Antidesma ghaesembilla

Two new dihydronaphthalenones (1, 2) with four known compounds (3–6) were isolated as secondary metabolites of the endophytic fungus Nodulisporium sp. from Antidesma ghaesembilla. Their chemical structures were established based on 1D and 2D NMR spectroscopic data and HR-ESI–MS analyses. The relative configuration of 2 was confirmed by single crystal X-ray crystallographic analysis. A new isofuranonaphthalenone 2 displayed antimycobacterial and antimalarial activities with IC₅₀ values of 3.125 and 11.3 μg/mL, respectively.     

Bioactive azaphilones from the fungus Penicillium multicolor CM01

Two new azaphilones, dechloroisochromophilone II (1) and epi-isochromophilone III (2), a new natural product, 5-hydroxy-4-methoxy-5,6-dihydro-2H-pyran-2-one (3), together with eleven known compounds, 4–14 were isolated from the fungus, Penicillium multicolor CM01. Their structures were elucidated by spectroscopic methods. Compounds 2, 8, 10 and 11 exhibited antimalarial activity against Plasmodium falciparum (IC₅₀ 2.1–7.8 μg/mL), while compounds 9 and 10 showed antimycobacterial activity against Mycobacterium tuberculosis (MIC 6.2 and 50.0 μg/mL, respectively). Compounds 2, 4, and 7–11 showed cytotoxicity against three cancer cell lines, KB, MCF-7 and NCI-H187 (IC₅₀ 2.2–35.2 μg/mL). In addition, compounds 1, 5–8 and 11 showed a minimum inhibition requirement to acetylcholinesterase (AChE) assay in the range of 0.03–0.25 nM.     

Cytosporone derivatives from the endophytic fungus Phomopsis sp. PSU-H188

Two new cytosporone derivatives (1 and 2) were isolated from the endophytic fungus Phomopsis sp. PSU-H188 together with 19 known compounds. Their structures were elucidated by analysis of spectroscopic data. Known mycoepoxydiene showed potent cytotoxic activity towards both MCF-7 and noncancerous Vero cell lines with the respective IC₅₀ values of 9.27 and 4.06 μM. It exhibited inhibition on glucose output in mouse primary hepatocytes with the IC₅₀ value of 16.06 μM, but did not show cytotoxicity on primary mouse hepatocytes. Additionally, known cytosporone B displayed protective activity against INS-1 832/13 pancreatic β-cells by an EC₅₀ value of 11.08 μM whereas known diaporthalasin displayed antibacterial activity against methicillin-resistant Staphylococcus aureus with an MIC value of 4 μg/mL. Both of them were noncytotoxic to Vero cells.     

New indole-diterpenoids from the algal-associated fungus Aspergillus nidulans

Two new compounds, including a chlorinated indole-diterpenoid 19-hydroxypenitrem A (1) and its dechlorinated derivative 19-hydroxypenitrem E (2), along with two known congeners (3 and 4), were isolated and identified from the cultures of Aspergillus nidulans EN-330, an endophytic fungus obtained from the marine red alga Polysiphonia scopulorum var. villum. Their structures and absolute configurations were assigned on the basis of 1D and 2D NMR and CD experiments. Compounds 1–4 exhibited cytotoxic activity against brine shrimp with LD₅₀ values of 3.2, 4.6, 1.7, and 8.7 μM, respectively. Besides, the chlorinated 19-hydroxypenitrem A (1) showed antimicrobial activity against four human- and aqua-pathogens. Preliminary SAR study revealed that the Cl-substitution at C-6 enhanced the cytotoxic activity against brine shrimp and antimicrobial activity, while the 19-OH substitution suppressed the activity.     

Adenylate cyclase from the phytopathogenic fungus Alternaria solani

Abstract Adenylate cyclase activity of Alternaria solani bound to the particulate cell fraction was solubilized by 2.5% Ficoll. The apparent K _m of the solubilized enzyme for adenosine 5'-triphosphate was 2.5 mM, and it required Mn²⁺ for maximum activity. M _r as determined by gel filtration was approximately 500. Fluoride ions at millimolar concentrations, GTP, adenosine, and N⁶-phenylisopropyl adenosine at micromolar concentrations did not stimulate adenylate cyclase activity. The enzyme was inhibited 25–55% by millimolar concentrations of 2'-deoxyadenosine, 2'-0 methyl adenosine, 9-β- d -arabinofuranosyl adenosine and 2'-3'-isopropylidene adenosine. Partially purified enzyme obtained after DEAE-BioGel chromatography was very unstable. The amount of extractable enzyme activity varied during the fungal growth cycle.     

Metabolites from the endophytic fungus Phomopsis sp. PSU-D15

From the endophytic fungus Phomopsis sp. PSU-D15, three metabolites named as phomoenamide (1), phomonitroester (2) and deacetylphomoxanthone B (3), were isolated together with three known compounds, dicerandrol A (4), (1S,2S,4S)-p-menthane-1,2,4-triol (5) and uridine. Their structures were elucidated by spectroscopic methods. Phomoenamide (1) exhibited moderate in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Ra.     

A double-stranded RNA mycovirus from the plant pathogenic fungus, Fusarium solani f. sp. robiniae

Abstract Two kinds of double-stranded RNA (dsRNA), estimated to be 1.9 and 1.7 kb in size, were detected in the plant pathogenic fungus, Fusarium solani f. sp. robiniae . Isometric virus-like particles (VLPs), 30 nm in diameter, were recovered from cell extracts as a discrete band when centrifuged through a CsCl density gradient. The dsRNA molecules extracted from VLP preparations were identical in electrophoretic mobility to the dsRNAs obtained directly from cells. SDS-PAGE analysis of the VLPs revealed a single polypeptide of 38 kDa. The dsRNAs obtained directly from cells. SDS-PAGE analysis of the asexual cycle).     

Diphenyl ether and benzophenone derivatives from the marine mangrove-derived fungus Penicillium sp. MA-37

Further investigation of the marine mangrove-derived fungal strain Penicillium sp. MA-37 led to the isolation of one new benzophenone, iso-monodictyphenone (1), two new diphenyl ether derivatives penikellides A (2) and B (3), and two known analogs monodictyphenone (4) and 6-[2-hydroxy-6-(hydroxymethyl)-4-methylphenoxy]-2-methoxy-3-(1-methoxy-3-methylbutyl)benzoic acid (5). The structures of these compounds were elucidated by spectroscopic analyses including 1D- and 2D-NMR and mass spectrometry. The brine shrimp lethality and antibacterial activity against five aquaculture pathogens were evaluated.     

Purification and characterization of a lectin from endophytic fungus Fusarium solani having complex sugar specificity

A lectin from the mycelial extract of an endophytic strain of Fusarium solani was purified. Its hemagglutinating activity was inhibited by glycoproteins possessing N-linked as well as O-linked glycans. The thermodynamics and kinetics of binding of glycans and glycoproteins to F. solani lectin was studied using surface plasmon resonance. The lectin showed high affinity for asialofetuin, asialomucin, asialofibrinogen, and thyroglobulin; and comparatively low affinity for mucin, fetuin, fibrinogen, and holotransferrin. Glycoproteins showed several fold higher affinity than their corresponding glycans with significant contribution from enthalpy and positive entropy, suggesting the involvement of non-polar protein-protein interaction. Moreover, the higher affinity of the glycoproteins was due to their faster association rates and low activation energy.     

Abietane Diterpenes from Hyptis suaveolens

Investigation of the constituents of the whole plant of Hyptis suaveolens led to the isolation of three new abietane diterpenes, isosuaveolic acid ( 1 ), 8α,9α‐epoxysuaveolic acid ( 2 ), and 14‐O‐methylsuaveolic acid ( 3 ), together with eleven known compounds. The structures of 1 – 3 were established by spectroscopic methods and chemical correlations. Some isolates were tested for their antimycobacterial and cytotoxic activities.     

Two new cycloartane-type triterpenoids and one new flavanone from the leaves of Dasymaschalon dasymaschalum and their biological activity

Two new cycloartane-type triterpenoids, 3β-hydroxy-21-O-acetyl-24-methylenecycloartane (3) and 3β,21-dihydroxy-24,31-epoxy-24-methylenecycloartane (4), one new flavanone, 7-hydroxy-6,8-dimethoxyflavanone (5), two new natural products, 2-hydroxybenzyl benzoate (7) and 2-phenyl-2-acetoxyethyl benzoate (8), and ten known compounds, 3β-hydroxy-24-methylenecycloartane (1), 3β,21-dihydroxy-24-methylenecycloartane (2), desmosdumotin B (6), artabotrene (9), (?)-senepoxide (10), (+)-crotepoxide (11), (?)-1,6-desoxypipoxide (12), rotundol (13), cassipourol (14) and (+)-spathulenol (15) were isolated from the leaves of Dasymaschalon dasymaschalum. The structures of the new compounds were elucidated by spectroscopic analysis and of the known compounds by comparison of their physical, UV, IR, ¹H and ¹³C NMR data with those of published compounds. Antimycobacterial, antiplasmodial and cytotoxic activities of the isolates, except 8 and 10 were evaluated. Compounds 1, 4, 5, 11, 12 and 15 exhibited potent cytotoxic activities against human lung cancer cell lines (NCI-H187) with respective IC₅₀ values of 4.67, 7.82, 1.85, 6.33, 3.07 and 6.68 μg/mL.     

New butenolide derivatives from the marine-derived fungus Paecilomyces variotii with DPPH radical scavenging activity

Bioassay-guided fractionation of the marine-derived endophytic fungus Paecilomyces variotii resulted in the isolation of two new butenolides, namely, butyrolactone IX (1) and aspulvinone O (7), together with eight known related congeners, butyrolactones I, IV, V, and VI (2–5), aspernolide A (6), and aspulvinones H, C, and D (8–10). Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with literature data. All of the isolated butenolides were tested for their activity against DPPH radicals and the results showed that butyrolactones (1–6) possessed potent activity with IC₅₀ values ranging from 38.0 to 186.3 μM, while aspulvinones (7–10) exhibited significant activities with IC₅₀ values ranging from 11.6 to 29.4 μM, which are stronger than that of the positive control BHT (with IC₅₀ 117.7 μM). The preliminary structure–activity relationship was discussed.     

Bioremediation of DDT in soil by genetically improved strains of soil fungus Fusarium solani

Bioremediation of DDT in soil by genetically improved recombinants of the soil fungus Fusarium solani was studied. The parent strains were isolated from soil enriched with DDD or DDE (immediate anaerobic and aerobic degradation products of DDT), as further degradation of these products are slow processes compared to the parent compound. These naturally occurring strains isolated from soil, however, are poor degraders of DDT and differed in their capability to degrade its metabolites such as DDD, DDE, DDOH and DBP and other organochlorine pesticides viz. kelthane and lindane. Synergistic effect was shown by some of these strains, when grown together in the medium containing DDD and kelthane under mixed culture condition. No synergism in DDE degradation was observed with the strains isolated from enriched soil. DDD-induced proteins extracted from individual culture filtrate (exo-enzyme) when subjected to SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) showed complementary polypeptide bands in these strains i.e., each strain produced distinct DDD degrading polypeptide bands and the recombinant or hybrid strains produced all of the bands of the two parents and degraded DDD better than the parental strains. Recombinant hybrid strains with improved dehalogenase activity were raised by parasexual hybridisation of two such complementary isolates viz. isolate 1(P-1) and 4(P-2) showing highest complementation and are compatible for hyphal fusion inducing heterokaryosis. These strains are genetically characterised as Kel⁺Ben^RDBP^-Lin^- and Kel^-Ben^rDBP⁺Lin⁺ respectively.Recombinants with mixed genotype, i.e., Kel⁺Ben^RDBP⁺Lin⁺ showing superior degradation quality for DDT were selected for bioremediation study. Recombination was confirmed by polypeptide band analysis of DDD induced exo-proteins from culture filtrate usingSDS-Polyacrylamide Gel Electrophoresis (PAGE) and RAPD (Random Amplified Polymorphic DNA) of genomic DNA using PCR (Polymerase Chain Reaction) technique. SDS-PAGE showed combination of DDD induced polypeptide bands characteristic of both the parents in the recombinants or the hybrids. PCR study showed the parent specific bands in the recombinant strains confirming gene transformation.     

Isolation, Structure elucidation, and antimycobacterial properties of dimeric naphtho-gamma-pyrones from the marine-derived fungus Aspergillus carbonarius

Two new dimeric naphtho-gamma-pyrones, compounds 1 and 2, were isolated from the AcOEt extract of the fungal strain WZ-4-11 of Aspergillus carbonarius, together with eight known analogues, including 10,10'-bifonsecin B (3), 6'-O-demethylnigerone (4), nigerone (5), isonigerone (6), fonsecin (7), rubrofusarin B (8), TMC 256A1 (9), and flavasperone (10). Their structures were elucidated by means of UV, CD, IR, and 1D- and 2D-NMR spectroscopy, in combination with HR-MS analysis. The fully assigned (1)H- and (13)C-NMR data of 3, and the (13)C-NMR data of 6 are reported for the first time. Compounds 1 and 2 showed weak antimycobacterial activities against Mycobacterium tuberculosis H37Rv, with MIC values of 43.0 and 21.5 microM, resp.