Phytochemical analysis and anti-infective potential of fungal endophytes isolated from Nigella sativa seeds.

Endophytic fungi, particularly from higher plants have proven to be a rich source of antimicrobial secondary metabolites. The purpose of this study is to examine the antimicrobial potential of three endophytic fungi Aspergillus sp. SA1, Aspergillus sp. SA2, and Aspergillus sp. SA3, cultivated from Nigella sativa seeds against Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (ATCC 13883), MRSA (ATCC 33591), and human pathogen Candida albicans (ATCC 10231). Furthermore, the most active cultivated endophytic fungi were molecularly identified via internal transcribed spacer (ITS) sequencing. HR-ESIMS guided approach has been used successfully in chemical profiling of 26 known bioactive secondary metabolites (1-26), which belongs to different classes of natural compounds such as polyketides, benzenoids, quinones, alcohols, phenols or alkaloids. Finally, in-silico interactions within active site of fungal Cyp51 and bacterial DNA gyrase revealed possibility of being a hit-target for such metabolites as antimicrobials.

Promising Cytotoxic butenolides from the Soybean endophytic fungus Aspergillus terreus: a combined molecular docking and in-vitro studies.

AIM: This study aimed to use one strain many compounds approach (OSMAC) to investigate the cytotoxic potential of Aspergillus terreus associated with soybean versus several cancer cell lines, by means of in-silico and in vitro approaches. METHODS AND RESULTS: Fermentation of the isolated strain was done on five media. The derived extracts were investigated for their inhibitory activities against three human cancer cell lines; mammary gland breast cancer (MCF-7), colorectal adenocarcinoma (Caco-2), and hepatocellular carcinoma (HepG2) using MTT Assay. The fungal mycelia fermented in Modified Potato Dextrose Broth (MPDB) was the most cytotoxic extract against HepG2, MCF-7, and Caco-2 cell lines with IC50 4.2 ± 0.13, 5.9 ± 0.013 and 7.3 ± 0.004 µg mL-1, respectively. MPDB extract was scaled up resulting in the isolation of six metabolites; three fatty acids (1, 2, and 4), one sterol (3) and two butenolides (5 and 6) by column chromatography. The isolated compounds (1-6) were screened through a molecular docking approach for their binding aptitude to various active sites. butyrolactone-I (5) revealed a significant interaction within the CDK2 active site, while aspulvinone E (6) showed promising binding affinity to FLT3 and EGFR active sites that was confirmed by in vitro CDK2, FLT3 and EGFR inhibitory activity. Finally, the in vitro cytotoxic activities of butyrolactone-I (5) and aspulvinone E (6) revealed the antiproliferative activity of butyrolactone-I (5), against HepG2 cell line (IC50 = 17.85 ± 0.32 µM). CONCLUSION: Molecular docking analysis and in vitro assays suggested the CDK2/A2 inhibitory potential of butyrolactone-I (5) in addition to the promising interaction abilities of aspulvinone E (6) with EGFR and FLT3 active sites as a possible mechanism of their biological activities.

Metabolomic profiling and cytotoxic potential of three endophytic fungi of the genera Aspergillus, Penicillium and Fusarium isolated from Nigella sativa seeds assisted with docking studies.

The main aim of our study is to investigate the anticancer potential of our cultivated entophytic fungal strains from Nigella sativa seeds. The strains were identified by sequencing of the partial 18S rRNA gene and the internal transcribed spacer (ITS) region as Aspergillus sp. (SA4), Penicillium sp. (SA5), and Fusarium sp. (SA6). We carried out metabolic profiling for three fungal strains to investigate their metabolites diversity. Profiling of the different extracts revealed their richness in diverse metabolites and consequently fourteen compounds (1-14) were annotated. In addition, the obtained extracts were examined against three cell lines HepG2, MCF-7 and Caco-2 showed activity with IC50 values in the range of 1.95-39.7 µg/mL. Finally, molecular docking study was performed showing questinol as the lowest glide binding score value (-5.925 kcal/mol) among all identified compounds. Our results showed Nigella sativa-associated endophytes as a promising source for further studies to look for anticancer secondary metabolites.

Metabolomic profiling and antioxidant potential of three fungal endophytes derived from Artemisia annua and Medicago sativa.

In this work, three fungal endophytes identified as Aspergillus terreus (AFL, AFSt and AFR), were studied for their antioxidant potential. LC-MS-based metabolomics, followed by multivariate statistical analysis were then applied to comprehensively profile their extracts. The three fungal endophytes revealed interesting antioxidant potential, in particular, the strain isolated from the Artemisia annua leaves (AFL), which was rich in different types of phenolic metabolites. Additionally, all fungal-derived ethyl acetate extracts showed potent inhibition against the prooxidant xanthine oxidase. Multivariate analysis (PCA and PLS-DA) demonstrated a unique chemical fingerprint for each strain, where phenolics, coumarins, and polyketides were the discriminative metabolites of the three fungal strains. The present findings highlighted the power of metabolomics in the chemotaxonomical classification of closely related strains. It also asserted the role of fungal endophytes in the management of oxidative stress, particularly when they are utilized in the production of fermented food products.