Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. II. Structure elucidation

The structures of citridones A, B, B' and C, new potentiators of miconazole activity against Candida albicans produced by Penicillium sp. FKI-1938, were elucidated by various spectroscopic analyses including UV, NMR, and MS and degradation experiments. Although citridones B and B' were isolated as a mixture, each structure was also elucidated, indicating that they exist in equilibrium of hemiacetal epimerization. Citridones A, B and B' have a similar phenylfuropyridone moiety.     

Yaequinolones, new insecticidal antibiotics produced by Penicillium sp. FKI-2140. II. Structural elucidation

The structure and relative stereochemistry of yaequinolones, fungal insecticidal antibiotics, were elucidated by spectroscopic studies, including NMR spectral analyses. Yaequinolones possess a p-methoxyphenylquinolinone skeleton modified with different isoprenyl-derived side chains.     

Yaequinolones, new insecticidal antibiotics produced by Penicillium sp. FKI-2140. I. Taxonomy, fermentation, isolation and biological activity

New nine insecticidal antibiotics designated yaequinolones were isolated from the culture broth of the fungal strain Penicillium sp. FKI-2140 by solvent extraction, centrifugal partition chromatography and HPLC. Yaequinolones showed growth inhibitory activity against brine shrimp (Artemia salina). Among them, yaequinolone F has the most potent activity with MIC value of 0.19 microg/ml.     

Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. I. Taxonomy, fermentation, isolation and biological properties

New phenylfuropyridinones and related compounds, designated citridones A, B, B' and C, were isolated along with known CJ-16,173, from the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel column chromatography and HPLC. Citridones (75 microM) potentiate the miconazole activity against Candida albicans, decreasing the IC50 value of miconazole from 14.5 nM to 3.5 to approximately 6.3 nM.     

Paecilaminol, a new NADH-fumarate reductase inhibitor, produced by Paecilomyces sp. FKI-0550

A new NADH-fumarate reductase inhibitor, paecilaminol, was isolated from the cultured broth of a fungus Paecilomyces sp. FKI-0550. It is an amino alcohol compound, the structure being established as 2-amino-14,16-dimethyl-3-octadecanol. Paecilaminol exhibited an IC50 value of 5.1 microM against Ascaris suum NADH-fumarate reductase.     

Verticipyrone, a new NADH-fumarate reductase inhibitor, produced by Verticillium sp. FKI-1083

A new NADH-fumarate reductase inhibitor, verticipyrone, was isolated from the cultured broth of a fungus, Verticillium sp. FKI-1083. The structure was established as (E)-2-methoxy-3,5-dimethyl-6-(3-methyl-2-undecenyl)-4H-pyran-4-one. Verticipyrone exhibited an IC50 value of 0.88 nM against NADH-fumarate reductase of Ascaris suum. Verticipyrone inhibited both Ascaris and bovine heart complex I, and its synthetic analogue, 8,9-dihydro-8-hydroxyverticipyrone, showed good selectivity against Ascaris complex I.     

New sesquicillins, insecticidal antibiotics produced by Albophoma sp. FKI-1778

Four new antibiotics, sesquicillins B to E were isolated from the culture broth of Albophoma sp. FKI-1778 together with known sesquicillin (sesquicillin A in this paper). The structures of sesquicillins were elucidated by spectroscopic studies including various NMR experiments. All sesquicillins have a common pyrano-diterpene skeleton. Sesquicillins showed moderate inhibitory activity against the growth of Artemia salina (brine shrimps) and Jurkat cells.     

New isochaetochromin, an inhibitor of triacylglycerol synthesis in mammalian cells, produced by Penicillium sp. FKI-4942: II. structure elucidation

The structure of a new congener of chaetochromin, an inhibitor of triacylglycerol synthesis in CHO-K1 cells produced by Penicillium sp. FKI-4942, was elucidated by spectroscopic methods, including various NMR experiments. Isochaetochromin A(1) has a bis-naphtho-γ-pyrone moiety.     

Stemphones, novel potentiators of imipenem activity against methicillin-resistant staphylococcus aureus, produced by Aspergillus sp. FKI-2136

A fungal strain FKI-2136 identified as genus Aspergillus was found to produce potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus (MRSA). Two new compounds designated stemphones B and C were isolated along with a structurally related known compound cochlioquinone D from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and preparative HPLC. These compounds have a common tetracyclic quinone skeleton. Stemphone C potentiated imipenem activity against the MRSA 512 fold by decreasing MIC value of imipenem from 16 microg/ml to 0.03 microg/ml.     

Tensidols, new potentiators of antifungal miconazole activity, produced by Aspergillus niger FKI-2342

Two new furopyrrols, designated tensidols A and B, were isolated from the culture broth of Aspergillus niger FKI-2342 by solvent extraction, silica gel column chromatography and HPLC. Their structures were elucidated and shown to have the common skeleton of 6-benzyl-6H-furo[2,3-b]pyrrole. Tensidols A and B potentiated miconazole activity against Candida albicans. Tensidols also showed moderate antimicrobial activity only against Pyricularia oryzae.     

In vitro and in vivo assessement of the antimalarial activity of sergeolide

The antimalarial activity of sergeolide (a quassinoid from PICROLEMMA PSEUDOCOFFEA) was investigated both, IN VITRO on PLASMODIUM FALCIPARUM cultures and IN VIVO through a classical test of schizontocidal action against PLASMODIUM BERGHEI in mice. Sergeolide showed a very strong antiplasmodial activity IN VITRO as well as IN VIVO. Low concentrations (0.006 microg/ml) were able to fully inhibit the IN VITRO growth of chloroquine-sensitive and resistant strains of P. FALCIPARUM. Small amounts (0.26 mg/kg/day) markedly reduced the virulence of experimentally induced P. BERGHEI infection in mice. However, sergeolide, because of its high toxicity (LD 50: 1.8 mg/kg), does not seem, in its present form to be useful for malaria curative treatment.     

New insecticidal antibiotics, hydroxyfungerins A and B, produced by Metarhizium sp. FKI-1079

New insecticidal antibiotics designated hydroxyfungerins A and B were isolated from the culture broth of a fungal strain Metarhizium sp. FKI-1079 together with a known compound, fungerin. The structures of hydroxyfungerins A and B were elucidated by spectroscopic studies including various NMR experiments. Hydroxyfungerins A and B showed growth inhibitory activity against brine shrimps, Artemia salina.     

In vitro and in vivo antimalarial activity of derivatives of 1,10-phenanthroline framework

A series of trisubstituted 1,10-phenanthrolines was prepared. These compounds exhibited mild to high biological activities in vitro both toward chloroquino-resistant FcB1-Columbia and FcM29-Cameron strains and Nigerian chloroquino-sensitive strain of Plasmodium falciparum. Cytotoxicity of the most active compounds was estimated showing that one compound (10) exhibited a selective activity against malaria parasite (selectivity indexes of 52 and 144). Antiplasmodial activity of this derivative was optimized by N-10 alkylation and the phenanthrolinium salt (15) submitted to an in vivo study using mice infected by P. vinckei petteri showing an ED50 of 7.86 mg/kg/day.     

Synthesis and in vitro and in vivo antimalarial activity of new 4-anilinoquinolines

A new series of 4-anilinoquinolines with two proton-accepting side chains has been synthesized. Antimalarial activity and levels of cytotoxicity upon both MRC-5 cells and macrophages were found to be highly dependent upon the features of these side chains. Several compounds were found to be active in the low nanomolar range, against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. From among them, a morpholino derivative cured mice infected by Plasmodium berghei and displayed a lower toxicity than amodiaquine upon mouse macrophages.     

Dinapinones, novel inhibitors of triacylglycerol synthesis in mammalian cells, produced by Penicillium pinophilum FKI-3864

Dinapinone A, a novel biaryl dihydronaphthopyranone, was isolated from the culture broth of Penicillium pinophilum FKI-3864 by solvent extraction, silica gel and ODS column chromatography and HPLC. Dinapinone A showed very potent inhibition of triacylglycerol (TG) synthesis in intact Chinese hamster ovary K1 (CHO-K1) cells with an IC(50) value of 0.097?μM. Dinapinone A was found to be a mixture of stereoisomers, resulting in its separation into dinapinones A1 and A2 by HPLC using a C30 reverse-phase column. Dinapinone A1 did not inhibit TG synthesis in CHO-K1 cells even at 12 μM, and dinapinone A2 showed less potent inhibition (IC(50); 0.65 μM) than dinapinone A; however, a mixture of isolated dinapinones A1 and A2 (a 1:1 ratio) recovered the potent TG inhibitory activity (IC(50); 0.054 μM). A similar effect of dinapinone on TG synthesis in intact Raji cells was also observed.     

New verticilides, inhibitors of acyl-CoA:cholesterol acyltransferase, produced by Verticillium sp. FKI-2679

Verticillium sp. FKI-2679, a soil isolate, was found to produce inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT) in a cell-based assay using ACAT1- and ACAT2-expressing CHO cells. Three new compounds, verticilides A2, A3 and B1, were isolated along with a known compound, verticilide A1, from the fermentation broth of the fungus by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Structure elucidation showed that these compounds were new cyclic depsipeptide. Verticilides A1, A2, A3 and B1 showed a degree of selectivity towards ACAT2, with IC(50)s 8.5-11-fold more potent than observed against ACAT1.     

New isochaetochromin, an inhibitor of triacylglycerol synthesis in mammalian cells, produced by Penicillium sp. FKI-4942: I. Taxonomy, fermentation, isolation and biological properties

A new bis-naphtho-γ-pyrone isomer named isochaetochromin A(1) was isolated along with known isochaetochromins B(1) and B(2) from the culture broth of Penicillium sp. FKI-4942 by solvent extraction, silica gel column chromatography and HPLC. Among them, isochaetochromin B(1) showed the most potent inhibitory activity of triacylglycerol synthesis with an IC(50) value of 5.6?μM, followed by isochaetochromins B(2) (IC(50), 11?μM) and A(1) (33?μM).     

Two new meroterpenoids produced by the endophytic fungus Penicillium sp. SXH-65

Two new meroterpenoids, arisugacins I (1) and J (2), together with five known meroterpenoids including arisugacin B (3), arisugacin F (4), arisugacin G (5), territrem B (6) and territrem C (7) were isolated from an endophytic fungus Penicillium sp. SXH-65. Their structures were determined by extensive spectroscopic experiments and comparison with literature data. Their cytotoxicities were evaluated against Hela, HL-60 and K562 cell lines, and only 3 and 4 exhibited weak cytotoxicities against Hela, HL-60 and K562 cell lines with IC₅₀ values ranging from 24 to 60 μM.     

Atpenins, new antifungal antibiotics produced by Penicillium sp. Production, isolation, physico-chemical and biological properties

Penicillium sp. FO-125, a soil isolate, was found to produce a new antifungal antibiotic complex named atpenin. Three components A4, A5 and B were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and HPLC. The molecular formula of atpenins A4, A5 and B were determined to be C15H22NO5Cl, C15H21NO5Cl2 and C15H23NO5, respectively, on the basis of high resolution electron impact mass spectrometry and elemental analysis. They are active against filamentous fungi, especially, Trichophyton sp.     

Atacamycins A-C, 22-membered antitumor macrolactones produced by Streptomyces sp. C38

Three new 22-membered macrolactone antibiotics, atacamycins A-C, were produced by Streptomyces sp. C38, a strain isolated from a hyper-arid soil collected from the Atacama Desert in the north of Chile. The metabolites were discovered in our HPLC-diode array screening and isolated from the mycelium by extraction and chromatographic purification steps. The structures were determined by mass spectrometry and NMR experiments. Atacamycins A, B and C exhibited moderate inhibitory activities against the enzyme phosphodiesterase (PDE-4B2), whereas atacamycin A showed a moderate antiproliferative activity against adeno carcinoma and breast carcinoma cells.