A new pentanorlanostane derivative, cladosporide A, as a characteristic antifungal agent against Aspergillus fumigatus, isolated from Cladosporium sp

In the course of searching for new antifungal agents, a new pentanorlanostane derivative, cladosporide A (1), was isolated along with ergosterol, ergosterol peroxide and 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) from Cladosporium sp. as a characteristic antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established as 3beta,22-dihydroxy-23,24,25,26,27-pentanorlanostane-29-al by spectroscopic and chemical investigation and X-ray crystallographic analysis. Inhibitory activity against A. fumigatus (IC80 0.5-4.0 microg/ml) was observed for cladosporide A (1), but no activity was observed against pathogenic yeasts, Candida albicans and Cryptococcus neoformans, and other pathogenic filamentous fungi, Aspergillus niger and A. flavus. The 4beta-aldehyde residue in 1 might be essential for the antifungal activity, since 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) showed no inhibition against the above four fungi.     

Hybrid isoprenoids from a reeds rhizosphere soil derived actinomycete Streptomyces sp. CHQ-64

Indotertine A (1), a hybrid isoprenoid with a condensed pentacyclic skeleton, together with two related hybrid isoprenoids, drimentines F (2) and G (3), were isolated from a reeds rhizosphere soil derived actinomycete Streptomyces sp. CHQ-64. Their structures including absolute configurations were elucidated by spectroscopic methods, X-ray single crystal diffraction analysis, and TDDFT ECD calculations. Drimentines G (3) showed strong cytotoxicity against human cancer cells lines with IC(50)'s down to 1.01 μM, while 1 and 2 showed no significant activity.     

Two new antimicrobial metabolites from the endophytic fungus, Seimatosporium sp

Two new acaranoic acids, named seimatoporic acid A and B (1, and 2), together with six known compounds, R-(-)-mellein (3), cis-4-hydroxymellein (4), trans-4-hydroxymellein (5), 4R-hydroxy-5-methylmellein (6), (-)-5-hydroxymethylmellein (7), and ergosterol (8) were isolated from an endophytic fungus, Seimatosporium sp, by a bioassay-guided procedure. The structures of the new compounds have been assigned from analysis of the 1H and 13C NMR spectra, DEPT, and by 2D COSY, HMQC, HMBC and NOESY experiments. A mixture of compounds 1 and 2 showed strong antifungal activity against Botrytis cinerea, Septoria tritici, and Pyricularia oryzae.     

Nitrogenous sesquiterpenes from the Thai marine sponge Halichondria sp.

Five nitrogenous sesquiterpenes having an isonitrile [(−)-axisonitrile-3], a formamide [(+)-axamide-3, axamide-2 and (3S^*,5R^*,6R^*,9R^*)-3-formamido-1(10)-cadinene], and an amine [(−)-halichamine] functionality were isolated from the Thai marine sponge Halichondria sp., together with two steroids, ergosterol and ergosterol peroxide. (−)-Axisonitrile-3 was isolated from the natural source for the first time, while (+)-axamide-3 and (−)-halichamine were new metabolites. The structures of these compounds were elucidated on the basis of their spectroscopic data and by chemical transformations. All sesquiterpenes were tested for their cytotoxic activity against six cancer cell lines (HeLa, HuCCA-1, A549, MOLT-3, HepG2, MDA-MB231). Only (−)-axisonitrile-3 showed strong activity to the HepG2 cell line with an IC₅₀ value of 1.3 μM.     

Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana

Three new prenylated xanthones, mangostenones C (1), D (2), and E (3), together with 16 known xanthones 4-19, were isolated from the young fruit (7-week maturity stage) of Garcinia mangostana. The structural elucidation of the new compounds was mainly established on the basis of 1D and 2D NMR and HR-MS spectroscopic analysis. Compound 1 showed cytotoxic properties against three human cancer cell lines, epidermoid carcinoma of the mouth (KB), breast cancer (BC-1), and small cell lung cancer (NCI-H187), with IC50 values of 2.8, 3.53, and 3.72 microg/ml, respectively. Among the isolates, alpha-mangostin (12), the major metabolite, exhibited the most potent effects against the BC-1 cells with an IC50 value of 0.92 microg/ml, an activity greater than that of the standard drug ellipticine (IC50 = 1.46 microg/ml). Compound 12 also showed the highest activity against KB cells, while gartanin (10) displayed the strongest activity against the NCI-H187 cells at the respective IC50 values of 2.08 microg/ml and 1.08 microg/ml.     

The structure of a new cardenolide diglycoside and the biological activities of eleven cardenolide diglycosides from Nerium oleander

A new cardenolide diglycoside (1) was isolated from Nerium oleander together with ten known cardenolide diglycosides 2-11. The structure of compound 1 was established on the basis of their spectroscopic data. The in vitro anti-inflammatory activity of compounds 1-11 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 2-5 were active at an IC(50) value of less than 0.8 μM. The cytotoxicity of compounds 1-11 was evaluated against three human cell lines normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). Compound 3 was active toward VA-13 cells, and compounds 2-5 were active toward HepG2 cells at IC(50) values of less than 1.3 μM. The multidrug resistance (MDR)-reversal activity of compounds 1-11 was evaluated on the basis of the amount of calcein in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 1 and 8 showed moderate effects on calcein accumulation.     

Panduratins D-I, novel secondary metabolites from rhizomes of Boesenbergia pandurata

Investigation of the non-polar fraction of Boesenbergia pandurata of Myanmar led to the identification of six novel secondary metabolites, panduratins D-I (1-6), together with known diastereomers, panduratins B1 (7) and B2 (8). Their structures were determined based on extensive spectroscopic analysis. The in vitro preferential cytotoxicity of all isolates was examined against human pancreatic PANC-1 cancer cells under nutrient-deprived conditions. All exhibited a mild activity.     

Antimicrobial,Antioxidant and Antiproliferative Secondary Metabolites from Inonotus nidus-pici

Inonotus nidus-pici is a sterile conk which produces macrofungus, a neglected Central-Eastern European relative of the prized Inonotus obliquus, also known as chaga. Investigation of the methanol extract of the poroid fungus I. nidus-pici resulted in the isolation of citropremide (1), 3,4-dihydroxybenzalacetone (2) , lanosterol (3), ergost-6,8,22-trien-3β-ol (4), and ergosterol peroxide (5). The structures of fungal compounds were determined on the basis of one- and two-dimensional NMR and MS spectroscopic analysis. Compounds 1–2 and 4–5 were evaluated for their antioxidant and antimicrobial properties against several bacterial and fungal strains. 3,4-dihydroxybenzalacetone (2) and ergost-6,8,22-trien-3β-ol (4) demonstrated moderate antimicrobial activity, while the former possessed notable antioxidant activity in DPPH assay. The antiproliferative examinations performed on three human cancer (MES-SA, MES-SA/Dx5, A431) cell lines demonstrated that compounds 4 and 5 have notable cytotoxic activity with IC values in micromolar range. The current study represents the first report on the chemical profile of I. nidus-pici, providing a comprehensive study on the isolation and structure determination of bioactive secondary metabolites of this macrofungus.     

Nitrile-Containing Fischerindoles from the Cultured Cyanobacterium Fischerella sp

Chemical investigation of the cultured cyanobacterium Fischerella sp. (SAG strain number 46.79) led to the isolation of four nitrile-containing indole alkaloids, namely 12-epi-fischerindole I nitrile (1), deschloro 12-epi-fischerindole I nitrile (2), 12-epi-fischerindole W nitrile (3), and deschloro 12-epi-fischerindole W nitrile (4) along with a known metabolite hapalosin. The structures were determined by detailed spectroscopic analyses on the basis of 1D and 2D NMR and HRESIMS data. All isolates were evaluated for cytotoxicity against human cancer cells and for 20S proteasome inhibition. Deschloro 12-epi-fischerindole I nitrile (2) was found to be weakly cytotoxic against HT-29 cells with an ED(50) value of 23 μM. Hapalosin showed weak cytotoxicity against HT-29 and MCF-7 cells with ED(50) values of 22 and 27 μM, respectively, as well as moderate 20S proteasome inhibition with an IC(50) value of 12 μM. Compounds 1-4 all contain a nitrile moiety instead of the isonitrile found in all fischerindoles reported to date. Compounds 3 and 4 also display a new carbon skeleton, in which a six-membered ring replaces the five-membered ring normally found in fischerindole-type alkaloids.     

Cytotoxic sterols from marine-derived fungus Pennicillium sp

A new sterol, ergosta-8(14), 22-diene-3,5,6,7-tetraol(3beta, 5alpha, 6beta, 7alpha, 22E) (1), together with four known sterols ergosta-8(9), 22-diene-3,5,6,7-tetraol (3beta, 5alpha, 6beta, 7alpha, 22E) (2), 5alpha,8alpha-epidioxy-24(S)-methylcholesta-6,22-diene-3beta-ol (3), 5alpha,8alpha-epidioxy-24(S)-methylcholesta-6,9(11), 22-triene-3beta-ol (4), 3beta,5alpha,9alpha-trihydroxyergosta-7,22-diene-6-one (5) was isolated from marine fungus Pennicillium sp. Their structures were determined based on chemical analysis and spectral methods (IR, 1D and 2D NMR, HR-FAB-MS). Compounds 1-5 were evaluated for cytotoxicity against human liver cancer cell (Hep G), and most of them exhibited potent activity. Compound 1 display the highest potency with IC50 values 10.4 microg mL-1.     

Cytotoxic metabolites from the Okinawan ascidian Diplosoma virens

The unstable isomeric compounds 5-hydroxy-7-prop-2-en-(E)-ylidene-7,7adihydro-2H-cyclopenta[b]pyran-6-one (1) and 5-hydroxy-7-prop-2-en-(Z)-ylidene-7,7adihydro-2H-cyclopenta[b]pyran-6-one (2), previously described as antimicrobial metabolites from the sponge Ulosa sp., were isolated and identified as major components of the ascidian Diplosoma virens. In this paper, full spectral data for 2 and complete 13CNMR data for 1, based on 2D NMR measurements, are provided for the first time. Compounds 1 and 2 showed cytotoxity against HCT116 cells (human colorectal cancer cells) by triggering apoptotic cell death.     

Cytotoxic and anti-oxidant activities of lanostane-type triterpenes isolated from Poria cocos

A new lanostane-type triterpene, 29-hydroxypolyporenic acid C (8), was isolated from the dried sclerotia of Poria cocos together with eight other known compounds pachymic acid (1), dehydropachymic acid (2), 3-acetyloxy-16alpha-hydroxytrametenolic acid (3), polyporenic acid C (4), 3-epi-dehydropachymic acid (5), 3-epi-dehydrotumulosic acid (6), tumulosic acid (7), and dehydrotumulosic acid (9). The compounds were identified by spectral analysis and comparison with spectroscopic data reported in the literatures. Although none of the nine (1 to 9) compounds showed promising antioxidant activity, 1 through 6 and 8 showed good cytotoxicity against human lung cancer cell line A549 and human prostate cancer cell line DU145. Interestingly, all these compounds exhibited better cytotoxicity towards A549 than DU145 cells.     

Synthesis and in vitro antitumor activity of 1,3,4-oxadiazole derivatives based on benzisoselenazolone

A series of novel 1,3,4-oxadiazole derivatives based on benzisoselenazolone has been prepared and tested for antiproliferative activity in vitro against the cells of human cancer cell lines: SSMC-7721 (human liver cancer cell), MCF-7 (human breast cancer cell) and A549 (human lung cancer cell). All the compounds obtained exhibited antiproliferative activity and showed selective cytotoxicity against different cancer cells. Compounds 7d and 7i showed significant antiproliferative activities against MCF-7 cells, with IC50 values of 1.07 and 1.76?μM respectively. Compound 7d were found to be the most potent compound against SSMC-7721 cells, with IC50 values 4.46?μM.     

含1,2,3-三氮唑基团的新型四氧杂杯[2]芳烃[2]嘧啶衍生物的合成与抗肿瘤活性研究

以4-氯-2-甲硫基-6-丙炔氧基嘧啶为原料,依次经Williamson醚合成、氧化和聚合反应制得新型四氧杂杯[2]芳烃[2]嘧啶母体(4),并通过点击化学反应合成了4个结构新颖的含1,2,3-三氮唑基团的四氧杂杯[2]芳烃[2]嘧啶衍生物(5a^5d),其结构经1H MNR,13C MNR和HR-MS(ESI)表征。采用MTT法研究了5a^5d对人宫颈癌细胞(Hela),人乳腺癌细胞(MCF-7),人肝癌细胞(HepG2)和人肺癌细胞(A549)的体外抗肿瘤活性。结果表明:化合物5a对MCF-7具有明显的抑制活性,在50μM浓度下抑制率可达82%,优于阳性对照药5-氟尿嘧啶。     

Cytotoxic Withaphysalins from Physalis minima

A novel withanolide, withaphysalin P ( 1 ) with a nine‐membered ring, and six other new withaphysalins, 2 – 7 , together with the three known withaphysalins 8 – 10 were isolated from Physalis minima L. The structures were deduced by means of spectroscopic analyses, and that of withaphysalin P ( 1 ) was confirmed by a single‐crystal X‐ray diffraction analysis. Plausible biosynthetic pathways were postulated (Scheme 1). All compounds were tested for their antiproliferative activities toward the human colorectal‐carcinoma HCT‐116 cells and human nonsmall‐cell lung‐cancer NCI‐H460 cells (Table 4). Compounds 1 – 3, 7 – 10, 7a , and 7b displayed moderate cytotoxic activity against the two human cancer cell lines.     

Design and Synthesis of Novel Thioureas Derived from 4‐(4‐Fluorophenoxy)aniline as Anticancer Agents

A new series of thiourea derivatives were obtained by the reaction of 4‐(4‐fluorophenoxy) aniline with different isothiocyanates. Their chemical structures were confirmed by ultraviolet (UV ), infrared (IR ), nuclear magnetic resonance (NMR ), and mass spectral data and elemental analysis. All the synthesized thiourea derivatives were evaluated for their in vitro cancer activity against the human breast cancer cell lines MCF ‐7 (human breast adenocarcinoma) and SKBr ‐3 (human epithelial breast adenocarcinoma). Most of the derivatives exhibited significant anticancer activity. Especially, compound 3 showed the most potent activity (IC₅₀ 20.1 μM ) against SKBr ‐3 when compared with the drugs 5‐fluorouracil and cisplatin, and, most importantly, it did not affect normal breast epithelial cells (4010).     

Copper (II)-Surfactant Complex and Its Nano Analog as Potential Antitumor Agents

The in vitro anticancer activity of copper cetyl trimethyl ammonium bromide (Cu-CTAB)-loaded cyclodextrin nanoparticles on Ehrlich ascites carcinoma (EAC), colon cancer cells (HCT 116), liver cancer cells (HepG-2), breast cancer cells (MCF-7), and cervix cancer cells (Hela) was investigated using MTT due assay. Cyclodextrin nanoparticles loaded with Cu-CTAB exerted in vitro anticancer activity against the previous human cancer cell lines comparable to the activity of free non-entrapped in nanoparticles macro-particle Cu-CTAB. The nano analog was synthesized by physical loading using grinding with ball mill. The ratio between Cu-CTAB and cyclodextrin oligosaccharide was 1 Cu-CTAB: 3 cyclodextrin. The particle size of the nano derivative was determined using the transmitted electron microscope (TEM).     

Rubratoxin C,a new nonadride derivative from an endophytic fungus Penicillium sp. F-14

One new nonadride derivative rubratoxin C （1） together with a known compound rubratoxin B （2） were isolated from an endophytic fungus Penicillium sp. F-14. Their structures were elucidated by various spectroscopic methods. Bioassays showed that 2 had moderate cytotoxic effect against HCT-8, BEL-7402, Ketr3, A2780, MCF-7 and BGC-823 human cancer cell lines, and 1 exhibited weak activity.     

Two novel alkaloids from the stem of Saprosma hainanense and their cytotoxic activities in vitro

Two novel alkaloids, saprosmine A (1) and saprosmine B (2), were isolated from the stem of Saprosma hainanense MERR., along with five known alkaloids: marcanine A (3); cleistopholine (4); 4-methoxycarbonyl-5,10-benzogquinolinequinone (5); liriodenine (6); and quinoline (7). The chemical structures were established on the basis of extensive spectroscopic (IR, 1D-NMR, 2D-NMR, MS) data analysis and by comparison with spectroscopic data reported in the literature. Compounds 1 to 6 were evaluated for in vitro cytotoxic activities against the SPC-A-1 (human lung cancer), BEL-7402 (human hepatocellular carcinoma), SGC-7901 (human gastric cancer), and K-562 (human myelogenous leukaemia) cancer cell lines. Compounds 1 and 2 exhibited weak cytotoxic activities against K-562 cells. Compounds 3 and 5 showed cytotoxic activities against all four cancer cell lines.     

Germacranolides from Carpesium divaricatum: Some New Data on Cytotoxic and Anti-Inflammatory Activity

Carpesium divaricatum Sieb. & Zucc., a traditional medicinal plant used as an inflammation-relieving remedy, is a rich source of terpenoids. At least 40 germacrane-type sesquiterpene lactones, representatives of four different structural groups, were isolated from the plant. Cytotoxicity against cancer cells in vitro is the most frequently described biological activity of the compounds. However, little is known about the selectivity of the cytotoxic effect. The anti-inflammatory activity of the germacranolides is also poorly documented. The objective of the present study was to assess the cytotoxic activity of selected C. divaricatum germacranolides-derivatives of 4,5,8,9-tetrahydroxy-3-oxo-germacran-6,12-olide towards cancer and normal cell lines (including cells of different p53 status). Moreover, to assess the anti-inflammatory effect of the compounds, the release of four proinflammatory cytokines/chemokines (IL-1β, IL-8, TNF-α and CCL2) by lipopolysaccharide-stimulated human neutrophils was measured by ELISA. The investigated sesquiterpene lactones demonstrated nonselective activity towards prostate cancer (Du145 and PC3) and normal prostate epithelial cells (PNT2) as well as against melanoma cells (A375 and HTB140) and keratinocytes (HaCaT). Cytotoxic activity against osteosarcoma cells was independent of their p53 status. In sub-cytotoxic concentrations (0.5–2.5 µM) the studied compounds significantly decreased cytokine/chemokine release by lipopolysaccharide-stimulated human leukocytes.