A detailed analysis of a Philippine specimen of the marine echinoderm Comanthus sp. yielded fifte... more A detailed analysis of a Philippine specimen of the marine echinoderm Comanthus sp. yielded fifteen compounds including four anthraquinones identified as 1'-deoxyrhodoptilometrin (1) along with its 6-O-sulfate derivative (3), and rhodoptilometrin (2) with its 6-O-sulfate derivative (4). In addition five naphthpyrones including comaparvin (5), 6-methoxycomaparvin (6), 6-methoxycomaparvin-5-methylether (7), 6-methoxycomaparvin-5-methylether-8-O-sulfate (8), and 6-hydroxycomaparvin-8-O-sulfate (9) were likewise isolated and identified. Further compounds include steroids and a nucleoside derivative. The structures of the isolated compounds were unambiguously elucidated based on HRESIMS analysis, 1D and 2D NMR, and by comparison with the literature. For compounds 2 and 4 the absolute configurations were identified for the first time using the Mosher reaction. Both compounds are (S)-(-) enantiomers. All isolated compounds were evaluated for their cytotoxic activities against cancer cells using the (MTT) assay and compared to the well known marine cancer drug candidate kahalalide F (EC50=6.3 µg/mL). 1'-Deoxyrhodoptilometrine (1) and an unseparable mixture of comaparvin (5) and 6-methoxycomaparvin (6) exhibited pronounced cytotoxicity against mouse lymphoma L5178Y cells with EC50 values of 2.3 and 5.2 µg/mL, respectively.
Fungal endophytes are microorganisms that live inside the interior tissues of living plants witho... more Fungal endophytes are microorganisms that live inside the interior tissues of living plants without bringing on any dangerous reactions [1]. Based on the total exploration results, endophytes are clearly a rich and solid wellspring of bioactive and novel compounds with tremendous restorative potential. As a part of our ongoing research focusing on the discovery of natural products from fungal endophytes [2], an endophytic fungal strain, Chaetomium globosum (HG423571), was isolated from the inner healthy tissues of Avena sativa (Gramineae) growing in Morocco. The aim of the present study was to extract, explore, and characterize natural products produced by Chaetomium globosum and to evaluate their antitubercular, antibacterial, and cytotoxic activities. The crude ethyl acetate (EtOAc) extract of solid rice cultures of Chaetomium globosum was subjected to liquid-liquid fractionation between 90% MeOH and n-hexane. The aqueous methanolic fraction was purified by different types of chromatography using different stationary phases (silica gel and Sephadex LH-20). Final purification was achieved by semi-preparative reversed-phase HPLC to afford four known compounds (1-4); the structures were elucidated by NMR spectroscopy and high-resolution ESI mass spectrometry. Compound 1 was isolated as a brown amorphous powder. Its UV spectrum showed O max (MeOH) at 207.1, 286.0, and 293.5 nm, suggesting the existence of an indole moiety in the structure. The molecular formula of 1 was deduced to be C 31 H 30 N 6 O 6 S 4 based on HR-ESI-MS, revealing a prominent peak at m/z 733.0994 [M + Na] + (calcd 733.1002, C 31 H 30 N 6 NaO 6 S 4) and indicating the presence of 20 degrees of unsaturation. For the 13 C NMR spectrum of 1, see Table 1. Further spectral data of 1, including 1 H and 13 C NMR (Table 1), together with 2D NMR such as 1 H-1 H COSY, HMBC, and HMQC, determine unambiguously the chemical structure of compound (1).
Bioactivity-guided chemical investigation of a co-culture of marine-derived micro-organisms has y... more Bioactivity-guided chemical investigation of a co-culture of marine-derived micro-organisms has yielded one new steroid, 7β-hydroxycholesterol-1β-carboxylic acid (1) with an unprecedented carboxylic acid group at C-1, together with three known steroidal metabolites (2-4). The chemical structures and stereochemistry of the isolated compounds were unambiguously determined based on extensive 1D, 2D NMR and HR-ESI-MS measurements. The isolated compounds were assessed for their cytotoxic activity against four different human tumour cell lines K562 (leukaemia), HCT116 (colon), A2780 (ovary) and its cisplatin-resistant mutant (A2780 CisR), and they revealed moderate activities with IC50 values ranging from 10.0 to 100.0 μM.
Journal of King Saud University - Science, Jul 1, 2020
Chemical exploration of mangrove-rhizosphere-associated fungus Emericella sp. strain SWR1718 (Asp... more Chemical exploration of mangrove-rhizosphere-associated fungus Emericella sp. strain SWR1718 (Aspergillaceae) was performed through various chromatographic workup procedures. The achieved results afforded one new natural compound, emericelactone E (1) in addition to known compounds (2-7). The planar structures of the purified compounds were unambiguously carried out using several spectroscopic methods. Both relative and absolute configurations of compound 1 were carefully determined based on NOESY experiments, coupling constants and comparing its optical rotation with related congeners. Moreover, a plausible biosynthetic pathway of 1 and its related derivatives is reported for the first time in our study. The cytotoxic potential of isolated metabolites was assessed toward three human tumor cell lines where some of them exhibited moderate activities compared to paclitaxel as a standard anticancer.
Three quercetin-3-O-glycosides (1–3) were obtained from the endophytic fungus Nigrospora oryzae i... more Three quercetin-3-O-glycosides (1–3) were obtained from the endophytic fungus Nigrospora oryzae isolated from leaves of the Nigerian mistletoe Loranthus micranthus. The compounds were unequivocally identified based on their one and two dimensional NMR spectra and on their mass spectra. A fourth flavonoid glycoside (4) was tentatively identified as a luteolin monoglycoside. Comparative HPLC analyses of extracts of the endophyte and of the host plant indicated that compounds (1–3) were present as minor constituents in the extract of the host plant Loranthus micranthus whereas the latter was dominated by different gallic acid and by catechin derivatives that were missing in the endophyte extract. The presence of flavonoid glycosides in a fungal endophyte is remarkable and is unequivocally confirmed here for the first time. So far, compounds (1–3) were only known as commonly occurring plant secondary metabolites. This study adds further evidence to the remarkable plasticity of fungal secondary metabolism which has repeatedly been shown to produce the same compounds as present in plants.
Chemical investigation of the mycelial extract of a mixed culture of two marine alga-derived fung... more Chemical investigation of the mycelial extract of a mixed culture of two marine alga-derived fungal strains of the genus Aspergillus has yielded one new cyclotripeptide, psychrophilin E (1), the recently reported oxepin-containing alkaloids, protuboxepin A (2) and oxepinamide E (3), together with three other polyketide derivatives (4-6). The chemical structure and relative and absolute configurations of psychrophilin E (1) were unambiguously established based on HRMS, 1D, 2D NMR and chiral-phase HPLC analysis of its hydrolysate. All the isolated compounds were assessed for their anti-proliferative activity against four different human cancer cell lines and some of them revealed selective activities.
Fortschritte der Chemie Organischer Naturstoffe, 2011
treatment of disease (2, 3). An analysis of the origin of drugs developed between 1981 and 2007 i... more treatment of disease (2, 3). An analysis of the origin of drugs developed between 1981 and 2007 indicated that almost half of the drugs approved since 1994 were based on natural products (2, 3). Over 20 new drugs launched into the pharmaceutical market between 2000 and 2005 represent natural products (2, 3), whereas more than 13 natural-product-related drugs were approved from 2004 to 2007; four of them represent the first members of new classes of drugs: the peptide ziconotide, and the small molecules ixabepilone, retapamulin, and trabectedin (ET-743) (Fig. 1) (3, 4). Interestingly, over a hundred natural-productderived compounds are currently undergoing clinical trials and at least a hundred similar substances are under preclinical development, with most of these derived from leads from plant and microbial sources (3). In spite of challenges facing drug discovery from plants, including the legal and logistical difficulties involved in the procurement of plant materials, and the lengthy and costly process of bioassay-guided fractionation and compound isolation, plants still provide new drug leads that prove to be of potential preclinical and/or clinical use against serious ailments such as cancer, malaria, Alzheimer's disease, and AIDS (5). The family Meliaceae (= Mahogany family, order Sapindales) is an angiosperm plant family of mostly trees and shrubs together with a few herbaceous plants. This family includes about 50 genera and 550 species, with a panotropical geographical distribution. Two genera, namely, Swietenia (Mahogany) and Khaya (African mahogany), are important sources of high-quality woods for building shelters and furniture due to their physical properties and also due to their resistance to insect invasion (6). The genus Aglaia Lour. (Fig. 2) is the largest genus of the family Meliaceae, comprising about 120 woody species ranging from small to large trees up to 40 m high, mainly distributed in the
The redox-sensitive nuclear factor kappa-B (NF-κB) signaling pathway is an important cellular pat... more The redox-sensitive nuclear factor kappa-B (NF-κB) signaling pathway is an important cellular pathway often misregulated in various cancer cells. Therefore, blockade of NF-κB signaling in cancer cells presents a promising strategy and enormous effort has been invested to identify potent and specific inhibitors. The aim of this study was the identification of new compounds derived from marine organisms that act as NF-κB inhibitors and to identify their mechanism of action. In the present work a bioassay-guided investigation of a Philippine specimen of the marine echinoderm Comanthus sp. yielded ten compounds evenly divided into anthraquinones and naphthopyrones. From these compounds only two naphthopyrones, comaparvin and 6-methoxycomaparvin exhibited noteworthy inhibitory activity against tumor necrosis factor-alpha (TNF-α) induced NF-κB activation in rat hepatoma cells and human breast cancer cells. Comaparvin at concentrations between 50 μM and 100 μM reduces chymotrypsin-like proteasomal activity, blocks nuclear translocation of NF-κB and effectively inhibits TNF-α induced IκB phosphorylation suggesting a role of this compound in targeting IκB kinase (IKK). Furthermore, comaparvin sensitized cancer cells to apoptotic effects mediated by the pro-inflammatory cytokine TNF-α. These results correlate with downregulation of TNF-α induced expression of protective NF-κB target genes like MnSOD, XIAP or A20. In conclusion we identified the naphthopyrone comaparvin isolated from the marine echinoderm Comanthus sp. as a new inhibitor of the NF-κB signaling pathway acting by targeting both proteasome function and IκB phosphorylation likely by direct inhibitory effect on IKKβ activity.
A new acylic jasplakinolide congener (2), another acyclic derivative requiring revision (4), toge... more A new acylic jasplakinolide congener (2), another acyclic derivative requiring revision (4), together with two jasplakinolide derivatives including the parent compound jasplakinolide (1) were isolated from the Indonesian marine sponge Jaspis splendens. The chemical structures of the new and known compounds were unambiguously elucidated based on HRESIMS and exhaustive 1D and 2D NMR spectral analysis as well as a comparison of their NMR data with those of jasplakinolide (1). The isolated jasplakinolides inhibited the growth of mouse lymphoma (L5178Y) cells in vitro with IC 50 values in the low micromolar to nanomolar range.
Chemical investigation of the sponge derived fungus Arthrinium sp. following fermentation on soli... more Chemical investigation of the sponge derived fungus Arthrinium sp. following fermentation on solid rice medium led to the isolation of two new meroterpenoidal alcohols spiroarthrinols A (1) and B (2) together with eighteen known compounds (3-20). The structures and relative configuration of the new compounds were unambiguously determined based on HRESIMS and extensive 1D and 2D NMR spectroscopic analyses. In addition, a plausible biosynthetic pathway for the new compounds spiroarthrinols A (1) and B (2) was postulated encompassing a mixed polyketide/terpenoid pathway. When assessed for their antiproliferative activity against Caco-2 cell lines, none of the isolated compounds showed significant cytotoxicity.
Phytochemical analysis of a crude ethyl acetate (EtOAc) extract derived from endophytic fungus Fu... more Phytochemical analysis of a crude ethyl acetate (EtOAc) extract derived from endophytic fungus Fusarium verticillioides strain WF18 afforded one new polyketide metabolite, fusaisocoumarin A (1), along with two known compounds, emodin (2) and sesquiterpenoid phytohormone (+)-abscisic acid (ABA) (3). Chemical structures of isolated compounds were elucidated based on HRESIMS together with 1D-and 2D-NMR spectroscopic analyses. Interestingly, all isolated compounds revealed pronounced antifungal activity against certain endophytic fungal strains namely; Aspergillus austroafricanus strain Eis.1, Aspergillus versicolor strain EIS2, Phoma fungicola strain AT100, Aspergillus tubingensis strain AN103 along with Candida albicans ATCC 90029 with MIC (minimum inhibitory concentration) range from 0.3 to 1.3 mg/mL. The biosynthesis of antifungal compounds and the phytohormone (+)-abscisic acid (ABA) illustrates an example of the crosstalks between the host plant and its endophyte in which the endophytic fungus produces metabolites defending the host plant against environmental stresses and also against other fungal phytopathogens.
respectively). SE11 caused a decrease in ERK phosphorylation which may be a consequence of the in... more respectively). SE11 caused a decrease in ERK phosphorylation which may be a consequence of the inhibition of EGF receptor kinase by this compound. Since an inhibition of the EGF receptor/MAPK pathway is an important target for diverse cytostatic drugs, we suggest that the anthraquinone derivative 1′-deoxyrhodoptilometrin (SE11) may be an interesting lead structure for the development of new anticancer drugs.
Abstract Chemical exploration of Crepis sancta (L.) Bornm. (Asteraceae) aerial parts afforded two... more Abstract Chemical exploration of Crepis sancta (L.) Bornm. (Asteraceae) aerial parts afforded two new eudesmane sesquiterpenes (1 and 2) together with three known congeners (3-5) and two known methylated flavonoids (6 and 7). Structure elucidation of the new compounds was unambiguously performed based on HRESIMS, 1D and 2D NMR spectroscopic analyses. All isolated compounds were subjected to an in vitro cytotoxicity assay against mouse lymphoma (L5178Y) cells, revealing moderate activities with IC50 ranging from 7.9 to 21.0 μM.
A detailed analysis of a Philippine specimen of the marine echinoderm Comanthus sp. yielded fifte... more A detailed analysis of a Philippine specimen of the marine echinoderm Comanthus sp. yielded fifteen compounds including four anthraquinones identified as 1'-deoxyrhodoptilometrin (1) along with its 6-O-sulfate derivative (3), and rhodoptilometrin (2) with its 6-O-sulfate derivative (4). In addition five naphthpyrones including comaparvin (5), 6-methoxycomaparvin (6), 6-methoxycomaparvin-5-methylether (7), 6-methoxycomaparvin-5-methylether-8-O-sulfate (8), and 6-hydroxycomaparvin-8-O-sulfate (9) were likewise isolated and identified. Further compounds include steroids and a nucleoside derivative. The structures of the isolated compounds were unambiguously elucidated based on HRESIMS analysis, 1D and 2D NMR, and by comparison with the literature. For compounds 2 and 4 the absolute configurations were identified for the first time using the Mosher reaction. Both compounds are (S)-(-) enantiomers. All isolated compounds were evaluated for their cytotoxic activities against cancer cells using the (MTT) assay and compared to the well known marine cancer drug candidate kahalalide F (EC50=6.3 µg/mL). 1'-Deoxyrhodoptilometrine (1) and an unseparable mixture of comaparvin (5) and 6-methoxycomaparvin (6) exhibited pronounced cytotoxicity against mouse lymphoma L5178Y cells with EC50 values of 2.3 and 5.2 µg/mL, respectively.
Fungal endophytes are microorganisms that live inside the interior tissues of living plants witho... more Fungal endophytes are microorganisms that live inside the interior tissues of living plants without bringing on any dangerous reactions [1]. Based on the total exploration results, endophytes are clearly a rich and solid wellspring of bioactive and novel compounds with tremendous restorative potential. As a part of our ongoing research focusing on the discovery of natural products from fungal endophytes [2], an endophytic fungal strain, Chaetomium globosum (HG423571), was isolated from the inner healthy tissues of Avena sativa (Gramineae) growing in Morocco. The aim of the present study was to extract, explore, and characterize natural products produced by Chaetomium globosum and to evaluate their antitubercular, antibacterial, and cytotoxic activities. The crude ethyl acetate (EtOAc) extract of solid rice cultures of Chaetomium globosum was subjected to liquid-liquid fractionation between 90% MeOH and n-hexane. The aqueous methanolic fraction was purified by different types of chromatography using different stationary phases (silica gel and Sephadex LH-20). Final purification was achieved by semi-preparative reversed-phase HPLC to afford four known compounds (1-4); the structures were elucidated by NMR spectroscopy and high-resolution ESI mass spectrometry. Compound 1 was isolated as a brown amorphous powder. Its UV spectrum showed O max (MeOH) at 207.1, 286.0, and 293.5 nm, suggesting the existence of an indole moiety in the structure. The molecular formula of 1 was deduced to be C 31 H 30 N 6 O 6 S 4 based on HR-ESI-MS, revealing a prominent peak at m/z 733.0994 [M + Na] + (calcd 733.1002, C 31 H 30 N 6 NaO 6 S 4) and indicating the presence of 20 degrees of unsaturation. For the 13 C NMR spectrum of 1, see Table 1. Further spectral data of 1, including 1 H and 13 C NMR (Table 1), together with 2D NMR such as 1 H-1 H COSY, HMBC, and HMQC, determine unambiguously the chemical structure of compound (1).
Bioactivity-guided chemical investigation of a co-culture of marine-derived micro-organisms has y... more Bioactivity-guided chemical investigation of a co-culture of marine-derived micro-organisms has yielded one new steroid, 7β-hydroxycholesterol-1β-carboxylic acid (1) with an unprecedented carboxylic acid group at C-1, together with three known steroidal metabolites (2-4). The chemical structures and stereochemistry of the isolated compounds were unambiguously determined based on extensive 1D, 2D NMR and HR-ESI-MS measurements. The isolated compounds were assessed for their cytotoxic activity against four different human tumour cell lines K562 (leukaemia), HCT116 (colon), A2780 (ovary) and its cisplatin-resistant mutant (A2780 CisR), and they revealed moderate activities with IC50 values ranging from 10.0 to 100.0 μM.
Journal of King Saud University - Science, Jul 1, 2020
Chemical exploration of mangrove-rhizosphere-associated fungus Emericella sp. strain SWR1718 (Asp... more Chemical exploration of mangrove-rhizosphere-associated fungus Emericella sp. strain SWR1718 (Aspergillaceae) was performed through various chromatographic workup procedures. The achieved results afforded one new natural compound, emericelactone E (1) in addition to known compounds (2-7). The planar structures of the purified compounds were unambiguously carried out using several spectroscopic methods. Both relative and absolute configurations of compound 1 were carefully determined based on NOESY experiments, coupling constants and comparing its optical rotation with related congeners. Moreover, a plausible biosynthetic pathway of 1 and its related derivatives is reported for the first time in our study. The cytotoxic potential of isolated metabolites was assessed toward three human tumor cell lines where some of them exhibited moderate activities compared to paclitaxel as a standard anticancer.
Three quercetin-3-O-glycosides (1–3) were obtained from the endophytic fungus Nigrospora oryzae i... more Three quercetin-3-O-glycosides (1–3) were obtained from the endophytic fungus Nigrospora oryzae isolated from leaves of the Nigerian mistletoe Loranthus micranthus. The compounds were unequivocally identified based on their one and two dimensional NMR spectra and on their mass spectra. A fourth flavonoid glycoside (4) was tentatively identified as a luteolin monoglycoside. Comparative HPLC analyses of extracts of the endophyte and of the host plant indicated that compounds (1–3) were present as minor constituents in the extract of the host plant Loranthus micranthus whereas the latter was dominated by different gallic acid and by catechin derivatives that were missing in the endophyte extract. The presence of flavonoid glycosides in a fungal endophyte is remarkable and is unequivocally confirmed here for the first time. So far, compounds (1–3) were only known as commonly occurring plant secondary metabolites. This study adds further evidence to the remarkable plasticity of fungal secondary metabolism which has repeatedly been shown to produce the same compounds as present in plants.
Chemical investigation of the mycelial extract of a mixed culture of two marine alga-derived fung... more Chemical investigation of the mycelial extract of a mixed culture of two marine alga-derived fungal strains of the genus Aspergillus has yielded one new cyclotripeptide, psychrophilin E (1), the recently reported oxepin-containing alkaloids, protuboxepin A (2) and oxepinamide E (3), together with three other polyketide derivatives (4-6). The chemical structure and relative and absolute configurations of psychrophilin E (1) were unambiguously established based on HRMS, 1D, 2D NMR and chiral-phase HPLC analysis of its hydrolysate. All the isolated compounds were assessed for their anti-proliferative activity against four different human cancer cell lines and some of them revealed selective activities.
Fortschritte der Chemie Organischer Naturstoffe, 2011
treatment of disease (2, 3). An analysis of the origin of drugs developed between 1981 and 2007 i... more treatment of disease (2, 3). An analysis of the origin of drugs developed between 1981 and 2007 indicated that almost half of the drugs approved since 1994 were based on natural products (2, 3). Over 20 new drugs launched into the pharmaceutical market between 2000 and 2005 represent natural products (2, 3), whereas more than 13 natural-product-related drugs were approved from 2004 to 2007; four of them represent the first members of new classes of drugs: the peptide ziconotide, and the small molecules ixabepilone, retapamulin, and trabectedin (ET-743) (Fig. 1) (3, 4). Interestingly, over a hundred natural-productderived compounds are currently undergoing clinical trials and at least a hundred similar substances are under preclinical development, with most of these derived from leads from plant and microbial sources (3). In spite of challenges facing drug discovery from plants, including the legal and logistical difficulties involved in the procurement of plant materials, and the lengthy and costly process of bioassay-guided fractionation and compound isolation, plants still provide new drug leads that prove to be of potential preclinical and/or clinical use against serious ailments such as cancer, malaria, Alzheimer's disease, and AIDS (5). The family Meliaceae (= Mahogany family, order Sapindales) is an angiosperm plant family of mostly trees and shrubs together with a few herbaceous plants. This family includes about 50 genera and 550 species, with a panotropical geographical distribution. Two genera, namely, Swietenia (Mahogany) and Khaya (African mahogany), are important sources of high-quality woods for building shelters and furniture due to their physical properties and also due to their resistance to insect invasion (6). The genus Aglaia Lour. (Fig. 2) is the largest genus of the family Meliaceae, comprising about 120 woody species ranging from small to large trees up to 40 m high, mainly distributed in the
The redox-sensitive nuclear factor kappa-B (NF-κB) signaling pathway is an important cellular pat... more The redox-sensitive nuclear factor kappa-B (NF-κB) signaling pathway is an important cellular pathway often misregulated in various cancer cells. Therefore, blockade of NF-κB signaling in cancer cells presents a promising strategy and enormous effort has been invested to identify potent and specific inhibitors. The aim of this study was the identification of new compounds derived from marine organisms that act as NF-κB inhibitors and to identify their mechanism of action. In the present work a bioassay-guided investigation of a Philippine specimen of the marine echinoderm Comanthus sp. yielded ten compounds evenly divided into anthraquinones and naphthopyrones. From these compounds only two naphthopyrones, comaparvin and 6-methoxycomaparvin exhibited noteworthy inhibitory activity against tumor necrosis factor-alpha (TNF-α) induced NF-κB activation in rat hepatoma cells and human breast cancer cells. Comaparvin at concentrations between 50 μM and 100 μM reduces chymotrypsin-like proteasomal activity, blocks nuclear translocation of NF-κB and effectively inhibits TNF-α induced IκB phosphorylation suggesting a role of this compound in targeting IκB kinase (IKK). Furthermore, comaparvin sensitized cancer cells to apoptotic effects mediated by the pro-inflammatory cytokine TNF-α. These results correlate with downregulation of TNF-α induced expression of protective NF-κB target genes like MnSOD, XIAP or A20. In conclusion we identified the naphthopyrone comaparvin isolated from the marine echinoderm Comanthus sp. as a new inhibitor of the NF-κB signaling pathway acting by targeting both proteasome function and IκB phosphorylation likely by direct inhibitory effect on IKKβ activity.
A new acylic jasplakinolide congener (2), another acyclic derivative requiring revision (4), toge... more A new acylic jasplakinolide congener (2), another acyclic derivative requiring revision (4), together with two jasplakinolide derivatives including the parent compound jasplakinolide (1) were isolated from the Indonesian marine sponge Jaspis splendens. The chemical structures of the new and known compounds were unambiguously elucidated based on HRESIMS and exhaustive 1D and 2D NMR spectral analysis as well as a comparison of their NMR data with those of jasplakinolide (1). The isolated jasplakinolides inhibited the growth of mouse lymphoma (L5178Y) cells in vitro with IC 50 values in the low micromolar to nanomolar range.
Chemical investigation of the sponge derived fungus Arthrinium sp. following fermentation on soli... more Chemical investigation of the sponge derived fungus Arthrinium sp. following fermentation on solid rice medium led to the isolation of two new meroterpenoidal alcohols spiroarthrinols A (1) and B (2) together with eighteen known compounds (3-20). The structures and relative configuration of the new compounds were unambiguously determined based on HRESIMS and extensive 1D and 2D NMR spectroscopic analyses. In addition, a plausible biosynthetic pathway for the new compounds spiroarthrinols A (1) and B (2) was postulated encompassing a mixed polyketide/terpenoid pathway. When assessed for their antiproliferative activity against Caco-2 cell lines, none of the isolated compounds showed significant cytotoxicity.
Phytochemical analysis of a crude ethyl acetate (EtOAc) extract derived from endophytic fungus Fu... more Phytochemical analysis of a crude ethyl acetate (EtOAc) extract derived from endophytic fungus Fusarium verticillioides strain WF18 afforded one new polyketide metabolite, fusaisocoumarin A (1), along with two known compounds, emodin (2) and sesquiterpenoid phytohormone (+)-abscisic acid (ABA) (3). Chemical structures of isolated compounds were elucidated based on HRESIMS together with 1D-and 2D-NMR spectroscopic analyses. Interestingly, all isolated compounds revealed pronounced antifungal activity against certain endophytic fungal strains namely; Aspergillus austroafricanus strain Eis.1, Aspergillus versicolor strain EIS2, Phoma fungicola strain AT100, Aspergillus tubingensis strain AN103 along with Candida albicans ATCC 90029 with MIC (minimum inhibitory concentration) range from 0.3 to 1.3 mg/mL. The biosynthesis of antifungal compounds and the phytohormone (+)-abscisic acid (ABA) illustrates an example of the crosstalks between the host plant and its endophyte in which the endophytic fungus produces metabolites defending the host plant against environmental stresses and also against other fungal phytopathogens.
respectively). SE11 caused a decrease in ERK phosphorylation which may be a consequence of the in... more respectively). SE11 caused a decrease in ERK phosphorylation which may be a consequence of the inhibition of EGF receptor kinase by this compound. Since an inhibition of the EGF receptor/MAPK pathway is an important target for diverse cytostatic drugs, we suggest that the anthraquinone derivative 1′-deoxyrhodoptilometrin (SE11) may be an interesting lead structure for the development of new anticancer drugs.
Abstract Chemical exploration of Crepis sancta (L.) Bornm. (Asteraceae) aerial parts afforded two... more Abstract Chemical exploration of Crepis sancta (L.) Bornm. (Asteraceae) aerial parts afforded two new eudesmane sesquiterpenes (1 and 2) together with three known congeners (3-5) and two known methylated flavonoids (6 and 7). Structure elucidation of the new compounds was unambiguously performed based on HRESIMS, 1D and 2D NMR spectroscopic analyses. All isolated compounds were subjected to an in vitro cytotoxicity assay against mouse lymphoma (L5178Y) cells, revealing moderate activities with IC50 ranging from 7.9 to 21.0 μM.
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