Three new sterigmatocystin analogues from marine-derived fungus Aspergillus versicolor MF359

During the systematic screening of active compounds from marine-derived fungi, the extract of a strain of Aspergillus versicolor MF359 isolated from a marine sponge of Hymeniacidon perleve was identified for detailed chemical investigation. Three new secondary metabolites, named hemiacetal sterigmatocystin (1), acyl-hemiacetal sterigmatocystin (2), and 5-methoxydihydrosterigmatocystin (3), together with a known compound, aversin (4), were characterized. 1 represents a first structure of sterigmatocystin hemiacetal from nature. The antibacterial activities of these identified compounds were evaluated against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Compound 3 showed activity against S. aureus and B. subtilis with MIC values of 12.5 and 3.125 μg/mL, respectively.     

Madurastatin B3, a rare aziridine derivative from actinomycete <Emphasis Type="Italic">Nocardiopsis</Emphasis> sp. LS150010 with potent anti-tuberculosis activity

Since the discovery of the first antibiotic, natural products have played an important role in chemistry, biology and medicine. To explore the potential of bioactive compounds from microbes isolated from the southeast of Tibet, China, a crude extract library was constructed and screened against Staphylococcus aureus. The strain Nocardiopsis sp. LS150010 was scaled up and subjected to further chemical studies, resulting in the identification of N-salicyloyl-2-aminopropan-1,3-diol (2) and its rare aziridine derivative, madurastatin B3 (1). Their structures were determined by detailed analysis of 1D, 2D NMR and HRMS data. Compounds 1 and 2 displayed significant inhibitory activity against S. aureus and methicillin resistant S. aureus, with MIC values of 6.25 µg/mL. Compound 1 also showed potent inhibitory activity against Bacillus subtilis and Escherichia coli, as well as activity in a Mycobacterium tuberculosis Bacillus Calmette-Guérin infected THP-1 cell model.     

Microbial transformation of 20(S)-protopanaxatriol by Absidia corymbifera and their cytotoxic activities against two human prostate cancer cell lines

Seven hydroxylates of 20(S)-protopanaxatriol (1) transformed by Absidia corymbifera AS 3.3387 were isolated and identified by spectral methods including 2D-NMR. Among them, 7β-hydroxyl-20(S)-protopanaxatriol (2), 7α-hydroxyl-20(S)-protopanaxatriol (3), and 7β, 15α-dihydroxyl-20(S)-protopanaxatriol (7) are new compounds. The metabolites 2, 6, 7, and 8 showed the more potent inhibitory effects against DU-145 and PC-3 cell lines than the substrate.     

Combination of 1,4-naphthoquinone with benzothiazoles had selective algicidal effects against harmful algae

A series of naphthoquinone-benzothiazole conjugates were synthesized as algicides, and their efficacies against harmful algal blooming species, such as Chattonella marina, Heterosigma akashiwo and Cochlodinium polykrikoides, were examined. The introduction of substituted benzothiazole at the C2 position of 1,4-naphthoquinone (compounds 1–9) resulted in higher algicidal activity against C. polykrikoides than the C6 conjugates (compounds 10–20). On the other hand, of the C6 conjugates, compounds 11 and 12 exhibited better algicidal activity against H. akashiwo, C. marina, and C. polykrikoides than the C2 conjugates. Further structure-activity analysis indicated that a replacement of the methoxy groups with hydroxyl groups (compounds 21–26) decreased the algicidal activity significantly. Among the various synthetic naphthoquinonebezothiazole conjugates tested, compound 12 was found to affect the most significant decrease in the level of C. polykrikoides growth, with an IC₅₀ of 0.19 μM. Compound 11 was found to be the most potent inhibitor against H. akashiwo and C. polykrikoides, with IC₅₀ values of 0.32 and 0.12 μM, respectively. Overall, these results highlight a possible method for controlling and inhibiting red tide forming algae using NQ derivatives.     

Antimicrobial Efficacy of Synthetic Pyranochromenones and (Coumarinyloxy)acetamides

Four (1, 2, 4 and 6) synthetic quaternary ammonium derivatives of pyranochromenones and (coumarinyloxy)acetamides were synthesized and investigated for their antimicrobial efficacy on MRSA (Methicillin-resistant Staphylococcus aureus), and multi-drug resistant Pseudomonas aeruginosa, Salmonella enteritidis and Mycobacterium tuberculosis H37Rv strain. One of the four compounds screened i.e. N,N,N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1), demonstrated significant activity against S. aureus, P. aeruginosa and M. tuberculosis with MIC value of 16, 35, and 15.62 µg/ml respectively. The cytotoxicity evaluation of compound 1 on A549 cell lines showed it to be a safe antimicrobial molecule, TEM study suggested that the compound led to the rupture of the bacterial cell walls.     

Isolation and Antibiotic Screening of Fungi from a Hydrothermal Vent Site and Characterization of Secondary Metabolites from a <Emphasis Type="Italic">Penicillium</Emphasis> Isolate

Five new compounds were isolated from Penicillium sp. Y-5-2 including an austin derivative 4, four isocoumarins 9, 11, 12, and 13, together with two known isocoumarins 8 and 10, and six known austin derivatives 1, 2, 3, 5, 6, and 7 and one phenol 14. Their structures and relative configurations were established by spectroscopic means. The absolute configurations of 4, 11, and 13 were defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. The cyclization of the pentan-2-ol pendant at C-3 in compound 13 allowed the assignment of a new 2,3,4,4a,6,10b-hexahydro-1H-benzo[c]chromene isocoumarin skeleton. New compounds 9, 11, and 13 revealed inhibitory activities against E. coli at MIC values around 32 μg/mL. The known compound 14 showed potent antibiotic activity against Staphylococcus aureus and Bacillus subtilis with MIC values 8 and 2 μg/mL, respectively, with no cytotoxicity when tested in vitro. A rapid and efficient technique for selecting antibiotic fungal strain among eight marine-derived fungi was also described.     

Two novel hydroperoxylated products of 20(S)-protopanaxadiol produced by Mucor racemosus and their cytotoxic activities against human prostate cancer cells

Microbial transformation of 20(S)-protopanaxadiol (1) by Mucor racemosus AS 3.205 yielded two novel hydroperoxylated metabolites and three known hydroxylated metabolites. The structures of the metabolites were identified as 26-hydroxyl-20(S)-protopanaxadiol (2), 23,24-en-25-hydroxyl-20(S)-protopanaxadiol (3), 25,26-en-24(R)-hydroperoxyl-20(S)-protopanaxadiol (4), 23,24-en-25-hydroperoxyl-20(S)-protopanaxadiol (5), and 25-hydroxyl-20(S)-protopanaxadiol (6). 4 and 5 are new compounds. Metabolites 2, 4, and 5 showed the more potent inhibitory effects against DU-145 and PC-3 cell lines than the substrate.     

Four anti-protozoal and anti-bacterial compounds from Tapirira guianensis

Tapirira guianensis is a common tree used in traditional medicine in French Guiana against several infectious diseases (malaria, leishmaniasis, bacteria, etc.). The bioassay-guided purification of CH₂Cl₂ bark extract led to the isolation of four cyclic alkyl polyol derivatives: 4,6,2′-trihydroxy-6-[10′(Z)-heptadecenyl]-1-cyclohexen-2-one (1a), 1,4,6-trihydroxy-1,2′-epoxy-6-[10′(Z)-heptadecenyl]-2-cyclohexene (1b), 1,4,5,2′-tetrahydroxy-1-[10′(Z)-heptadecenyl]-2-cyclohexene (2), and 1,3,4,6-tetrahydroxy-1,2′-epoxy-6-[10′(Z)-heptadecenyl]-cyclohexane (3). The structures were established on the basis of 1D and 2D NMR analyses. The anti-leishmanial, anti-plasmodial, anti-bacterial (on Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli), and anti-fungal (on Candida albicans) activities of the extracts and of these original compounds were evaluated. Two showed medicinal interest supporting the traditional uses of the plant. The structures were established through spectral analyses of the isolates and their derivatives.     

Anticancer and antifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2-14). The copper(II) complexes (2a-14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, ¹H and ¹³C NMR, AAS, UV-Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2-8 and 2a-8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G₂. Several derivatives were shown to be active comparable to that of cisplatin.     

Synthesis, crystal structures and in vitro antibacterial activity of two novel organotin(IV) complexes

Two triorganotin(IV) carboxylates [nBu₃SnOL]_n (KK1) and [Ph₃SnOL]_n (KK2) have been prepared by the reactions of (E)-3-(4-(diphenylamino)phenyl)acrylic acid (HL) with n(Bu₃Sn)₂O and Ph₃Sn(OH), respectively. Complexes KK1 and KK2 have been structurally characterized by IR, elemental analysis and X-ray crystallography, confirming that both complexes possess infinite 1D chain structures. It’s exciting to discover that KK1 and KK2 exhibit strong solid-state luminescence emission while the HL almost quenches. Furthermore, both complexes were assayed for in vitro antibacterial activity against two Gram-positive bacterial strains (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and two Gram-negative bacterial strains (Pseudomonas aeruginosa ATCC 13525 and Escherichia coli ATCC 35218) by MTT method. Complex KK2 exhibited powerful antibacterial activities against S. aureus with MIC value of 0.78 μg/mL, which was superior to the positive controls penicillin G. On the basis of the biological results, structure-activity relationships were discussed.     

Di- and polynuclear silver(I) saccharinate complexes of tertiary diphosphane ligands: synthesis, structures, in vitro DNA binding, and antibacterial and anticancer properties

A series of new silver(I) saccharinate (sac) complexes, [Ag₂(sac)₂(μ-dppm)H₂O]·H₂O (1), {[Ag₂(μ-sac)₂(μ-dppe)]·3H₂O·CH₂Cl₂} _n (2), [Ag₂(μ-sac)₂(μ-dppp)] _n (3), and [Ag(sac)(μ-dppb)] _n (4) [dppm is 1,1-bis(diphenylphosphino)methane, dppe is 1,2-bis(diphenylphosphino)ethane, dppp is 1,3-bis(diphenylphosphino)propane, and dppb is 1,4-bis(diphenylphosphino)butane], have been synthesized and characterized by C, H, N elemental analysis, IR spectroscopy, ¹H NMR, ¹³C NMR, and ³¹P NMR spectroscopy, electrospray ionization mass spectrometry, and thermogravimetry–differential thermal analysis. Single-crystal X-ray studies show that the diphosphanes act as bridging ligands to yield a dinuclear complex (1) and one-dimensional coordination polymers (2 and 4), whereas the sac ligand adopts a μ₂-N/O bridging mode in 2, and is N-coordinated in 1 and 4. The interaction of the silver(I) complexes with fish sperm DNA was investigated using UV–vis spectroscopy, fluorescence spectroscopy, and agarose gel electrophoresis. The binding studies indicate that the silver(I) complexes can interact with fish sperm DNA through intercalation, and complexes 1 and 3 have the highest binding affinity. The gel electrophoresis assay further confirms the binding of the complexes with the pBR322 plasmid DNA. The minimum inhibitory concentrations of the complexes indicate that complex 1 exhibits very high antibacterial activity against standard bacterial strains of Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus, being much higher than those of AgNO₃, silver sulfadiazine, ciprofloxacin, and gentamicin. Moreover, complexes 1–3 exhibit very high cytotoxic activity against A549 and MCF-7 cancer cell lines, compared with AgNO₃ and cisplatin. The bacterial and cell growth inhibitions of the silver(I) complexes are closely related to their DNA binding affinities.     

Production of macrolide antibiotics from a cytotoxic soil <Emphasis Type="Italic">Streptomyces</Emphasis> sp. strain ZDB

Crude extract from a culture of a soil Streptomyces sp. strain ZDB showed toxicity towards Artemia salina and antimicrobial activity against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Chlorella vulgaris, and Chlorella sorokiniana. Large scale fermentation of the strain led to the isolation of the macrolide antibiotics, bafilomycins A1 (1), B1 (2), and D (3) together with nonactic acid (4) and bostrycoidin-9-methyl ether (5). Structures of the antibiotics were determined based on spectral data analysis. We describe the isolation of the compounds and characterization of the producing strain.     

Antibacterial clerodane diterpenes from Goldenrod (Solidago virgaurea)

Nine clerodane diterpenes, solidagoic acids C-I (1-7), cleroda-3,13(14)-dien-16,15:18,19-diolide (8) and cleroda-3,13(14)-dien-15,16:18,19-diolide (9) were isolated and characterised from the ethanol-ethyl acetate (1:1) extract of Solidago virgaurea. The structures were determined by NMR spectroscopic analysis. Several displayed moderate antibacterial activity against Staphylococcus aureus.     

Mono- and digalactosyldiacylglycerols: potent nitric oxide inhibitors from the marine microalga Nannochloropsis granulata

Chemical investigation of a marine microalga, Nannochloropsis granulata, led to the isolation of four digalactosyldiacylglycerols namely, (2S)-1-O-eicosapentaenoyl-2-O-palmitoyl-3-O-(β-d-galactopyranosyl-6-1α-d-galactopyranosyl)-glycerol (1), (2S)-1-O-eicosapentaenoyl-2-O-palmitoleoyl-3-O-(β-d-galactopyranosyl-6-1α-d-galactopyranosyl)-glycerol (2), (2S)-1-O-eicosapentaenoyl-2-O-myristoyl-3-O-(β-d-galactopyranosyl-6-1α-d-galactopyranosyl)-glycerol (3), and (2S)-1,2-bis-O-eicosapentaenoyl-3-O-(β-d-galactopyranosyl-6-1α-d-galactopyranosyl)-glycerol (4), together with their monogalactosyl analogs (5–8). Among the isolated galactolipids 2 and 3 were new natural products. Complete stereochemistry of 1, 4, 5, 7, and 8 was determined for the first time by both spectroscopic techniques and classical degradation methods. Both mono- and digalactosyldiacylglycerols isolated from N. granulata possessed strong nitric oxide (NO) inhibitory activity against lipopolysaccharide-induced NO production in RAW264.7 macrophage cells through downregulation of inducible nitric oxide synthase expression indicating the possible use as anti-inflammatory agents.     

Synthesis of Pyrrolo[2′,3′:4,5]Furo[3,2-c]Pyridine-2-Carboxylic Acids

1H-Pyrrolo[2′,3′:4,5]furo[3,2-c]pyridine-2-carboxylic acid (6a) and its 1-methyl (6b) and 1-benzyl (6c) derivatives were synthesized. 3-(5-Methoxycarbonyl-4H-furo[3,2-b]-pyrrole-2-yl)propenoic acid (1) was converted to the corresponding azide 2, which in turn was cyclized to give 3 by heating in diphenylether. The pyridone 3 obtained was aromatized with phosphorus oxychloride, then reduced with zinc in acetic acid to give methyl 1H-pyrrolo[2′,3′:4,5]furo[3,2-c]pyridine-2-carboxylate (5), which by hydrolysis gave the corresponding carboxylic acid 6a.     

Antimicrobial ergosteroids and pyrrole derivatives from halotolerant Aspergillus flocculosus PT05-1 cultured in a hypersaline medium

In order to obtain more structurally novel and bioactive lead compounds for subsequent drug discovery, we have shifted the focus of our study from traditional microbial resources to ‘extremophiles’. In this study, a halotolerant fungus Aspergillus flocculosus PT05-1 was isolated from the sediment of Putian saltern of Fujian Province of China in a hypersaline medium. Two new compounds, (22R,23S)-epoxy-3β,11α,14β,16β-tetrahydroxyergosta-5,7-dien-12-one (1) and 6-(1H-pyrrol-2-yl)hexa-1,3,5-trienyl-4-methoxy-2H-pyran-2-one (5) (existed as a pair of epimers with the configuration of 1E,3Z,5E and 1E,3E,5E separately), along with nine known compounds were isolated and identified from the fermentation broth of A. flocculosus PT05-1 grown at a 10 % saline medium. New ergosteroid 1 together with 7-nor-ergosterolide (2) and 3β-hydroxyergosta-8,24(28)-dien-7-one (3) showed cytotoxicity against HL-60 and BEL-7402 cells with IC₅₀ values of 12–18 μM, and antimicrobial activity against Enterobacter aerogenes, Pseudomonas aeruginosa, and Candida albicans with MIC values of 1.6–15 μM, respectively. New compound 5 exhibited antibacterial effect on E. aerogenes with MIC value of 3.7 μM. This study also showed great prospects in developing medicinal resources from extremophiles.     

Design and synthesis of an indol derivative as antibacterial agent against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

Several indole derivatives with antibacterial activity have been prepared using different protocols; however, some require special reagents and conditions. The aim of this study involved the synthesis of some indole derivatives using estrone and OTBS-estrone as chemical tools. The synthesis of the indole derivatives involves reactions such as follows: (1) synthesis of two indol derivatives (4 or 5) by reaction of estrone or OTBS-estrone with phenylhydrazine in medium acid; (2) reaction of 4 or 5 with 6-cloro-1-hexyne in medium basic to form two hexynyl-indol (7 or 8); (3) preparation of indol-propargylic alcohol derivatives (10 or 11) by reaction of benzaldehyde with 7 or 8 in medium basic; (4) synthesis of indol-aldehydes (12 or 13) via oxidation of 10 or 11 with DMSO; (5) synthesis of indeno-indol-carbaldehyde (15 or 16) via alkynylation/cyclization of 12 or 13 with hexyne in presence of copper(II); (6) preparation indeno-indol-carbaldehyde complex (19 or 20) via alkynylation/cyclization of 12 or 13 with 1-(hex-5-yn-1-yl)-2-phenyl-1H-imidazole. The antibacterial effect exerted by the indol-steroid derivatives against Streptococcus pneumoniae and Staphylococcus aureus bacteria was evaluated using dilution method and the minimum inhibitory concentration (MIC). The results showed that only the compound 19 inhibit the growth bacterial of S. aureus. In conclusion, these data indicate that antibacterial activity of 19 can be due mainly to functional groups involved in the chemical structure in comparison with the compounds studied.     

Synthesis and antimicrobial evaluation of bile acid tridentate conjugates

Two series of novel bile acid tridentate conjugates with different linkers were synthesized and characterized, and their biological activities in vitro were evaluated. The procedure was straightforward and efficient to be carried out with high overall yield. The antimicrobial activity of the synthesized compounds against Saccharomyces cerevisiae, Aspergillus niger, Escherichia coli and Staphylococcus aureus was investigated in vitro. The best activity of minimal inhibitory concentrations (MICs) for 1c, 1c′, 2c and 2c′ against S. cerevisiae was up to 0.125 μg/mL.     

Synthesis, characterization and biological studies of organotin(IV) complexes with hydrazone ligand

Four organotin(IV) complexes with general formula [RSnCl_n−1(TCB)] [R = Ph₂, n = 2 (2); R = Me, n = 3 (3); R = Bu, n = 3 (4); R = Ph, n = 3 (5)] have been synthesized by direct reaction of thiophene-2-carboxaldehyde benzhydrazone ligand [HTCB, (1)], base and organotin(IV) chloride in absolute methanol under N₂ atmosphere. All organotin(IV) complexes were characterized by elemental analyses, molar conductivity, UV-Vis, FT-IR, ¹H and ¹³C NMR spectral studies. Among them, diphenyltin(IV) complex (2) has also been characterized by X-ray crystallography diffraction analyses. The cytotoxicity of the hydrazone ligand as well as its organotin(IV) complexes (2-5) were determined with Artemia salina. While no-choice bioassay was employed on Coptotermes sp. to evaluate the termiticidal effect of all the complexes. Besides, the ligand (1) and its organotin(IV) complexes (2-4) were also tested against five types of bacteria namely Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi.     

Synthesis of some quinolinyl chalcone analogues and investigation of their anticancer and synergistic anticancer effect with doxorubicin

Two derivatives of 2-(4-acetylanilino)quinolines (IIIa, b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va, b) were further manipulated into cyclic ??,??-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI?CVII). Deethoxycarboxylation of derivatives (VIIa, b) afforded cyclohexenons (VIIIa, b) allowing formation of a mini library of ??,??-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC₅₀ of 5.0 and 2.5 ??M respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 ??M.