Metabolomic tools to assess the chemistry and bioactivity of endophytic aspergillus strain

Endophytic fungi associated with medicinal plants are a potential source of novel chemistry and biology that may find applications as pharmaceutical and agrochemical drugs. In this study, a combination of metabolomics and bioactivity-guided approaches were employed to isolate anticancer secondary metabolites from an endophytic Aspergillus aculeatus. The endophyte was isolated from the Egyptian medicinal plant Terminalia laxiflora and identified using molecular biological methods. Metabolomics and dereplication studies were accomplished by utilizing the MZmine software coupled with the universal Dictionary of Natural Products database. Metabolic profiling, with aid of multivariate data analysis, was performed at different stages of the growth curve to choose the optimised method suitable for up-scaling. The optimised culture method yielded a crude extract abundant with biologically-active secondary metabolites. Crude extracts were fractionated using different high-throughput chromatographic techniques. Purified compounds were identified by HRESI-MS, 1D and 2D-NMR. This study introduced a new method of dereplication utilising both high-resolution mass spectrometry and NMR spectroscopy. The metabolites were putatively identified by applying a chemotaxonomic filter. We also present a short review on the diverse chemistry of terrestrial endophytic strains of Aspergillus, which has become a part of our dereplication work and this will be of wide interest to those working in this field. This article is protected by copyright. All rights reserved

Anthraquinones and naphthopyrones from the marine echinoderm comanthus sp

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

Protein kinase inhibitors from Indonesian sponge Axynissa sp

This article discusses protein kinase inhibitors from Indonesian sponge Axynissa sp

Isolation and structure identification of new alkaloids from the sponge Rhabdastrella rowi

Has conducted research on chemical components Rhabdastrella rowi sea sponges were collected from Bali, Indonesia. Penelitian ini bertujuan untuk mengisolasi dan mengidentifikasi struktur metabolit sekunder spons tersebut dan menguji aktivitas sitotoksisnya terhadap kultur sel limfoma tikus L5178Y. This study aimed to isolate and identify the structure of the secondary metabolites of sponges and test sitotoksisnya activity against L5178Y mouse lymphoma cell culture. Isolasi dilakukan dengan menggunakan berbagai tehnik kromatografi. Isolation was done by using various chromatographic techniques. Metode spektroskopi resonansi magnetic inti serta spektrometri massa digunakan untuk mengidentifikasi struktur kimia isolat. Method of magnetic resonance spectroscopy and mass spectrometry core is used to identify the chemical structure of isolates. Pengujian sitotoksisitas pada kultur sel limfoma tikus L5178Y dilakukan dengan menggunakan MTT assay. Cytotoxicity test on L5178Y mouse lymphoma cell culture by using MTT assay

Callyaerin g, a new cytotoxic cyclic peptide from the marine sponge callyspongia aerizusa

From the ethyl acetate fraction of the Indonesian sponge Callyspongia aerizusa extract, a new cyclic peptide named callyaerin G was isolated. Its structure was elucidated by extensive 1D and 2D NMR (1H NMR, TOCSY and ROESY) studies and mass spectrometric data (ESI- and FAB-MS). The stereochemistry was determined by Marfey's analysis. Callyaerin G was found to exhibit cytotoxic activity when tested against different cancer cell lines

Protein kinase inhibitors from the endophytic fungus stemphylium globuliferum

The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded eight new secondary metabolites, alterporriol F, alterporriol G and its atropisomer H, alterporriol I and its atropisomer J, altersolanol K, altersolanol L and stemphypyrone, beside eight known compounds. The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H exhibited considerable cytotoxicity against L5178Y cells with an EC50 value of 2.7 µg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for protein kinase inhibitory activity in an assay involving 24 different kinases. Compounds methylalaternin, macrosporin, altersolanol A and the mixture of alterporriol G and H were the most potent and also selective inhibitors, displaying EC50 values between 0.64 and 1.4 µg/mL toward individual kinases

Protein kinase inhibitors from the endophytic fungus alternaria sp isolated from polygonum senegalense growing in egypt

Protein kinases, which function as components of signal transduction pathways, play a central role in diverse biological processes, such as control of cell growth, metabolism, differentiation, and apoptosis [1]. Identification of the key roles of protein kinases in cancer has led to extensive efforts to develop kinase inhibitors for the treatment of a wide range of cancers [2]. In continuation of our efforts to discover natural protein kinase inhibitors we studied extracts of liquid and rice cultures of the fungal endophyte Alternaria sp. isolated from the Egyptian medicinal plant Polygonum senegalense. Chromatographic separation of the extracts yielded the known compounds alternariol (1), alternariol 5-O-methyl ether (2), altenusin (3), 2,5-dimethyl-7-hydroxychromone (4), tenuazonic acid (5), altertoxin I (6), talaroflavone (7), and altenuene (8), in addition to seven new metabolites (9-15). The structures of the compounds were unambiguously established on the basis of NMR spectroscopic and mass spectrometric data. Compounds 1-3, 9, and 12 showed cytotoxic activity toward L5178Y mouse lymphoma cell line with EC50 values ranging from 1.7 to 7.8µg/mL. When analyzed in vitro for their inhibitory potential against 24 different protein kinases, compounds 1-3, 6, 9, and 11-13 inhibited several of these enzymes (IC50 values 0.22-9.8µg/mL)