Niosomes as promising approach for enhancing the cytotoxicity of Hemimycale sp. total crude extract supported with in-silico studies.

The crude extract of Hemimycale sp. marine sponge was evaluated as a cytotoxic drug against different cell lines; whereas it exhibited promising selective activity toward the breast cancer cell line only with IC50 value 199.6 ± 0.00512 µg/ml. Moreover, its cytotoxic activity against the breast cancer cell line was reevaluated upon forming total extract-loaded niosomes. This revealed an IC50 value of 44.35 ± 0.011128 µg/ml, indicating the potential contribution of niosomes in boosting cell penetration and activity as a result. Owing to highlight the bioactive constituents responsible for the cytotoxic activity, metabolomics profiling of Hemimycale sp. was performed using liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) revealing tentative identification of phytoconstituents clusters like as, diterpenes, sesterterpenes and sterols. Additionally, the cytotoxic activity of the crude extract was explained on the molecular level, whereas the dereplicated compounds were evaluated in silico against the Epidermal Growth Factor Receptor tyrosine kinase (EGFR). The sesterterpenoid derivatives phorbaketal A acetate (12) and secoepoxy ansellone A (13) together with mycalol-522 (17) showed the best binding energy.

Evaluation of the anti-infective potential of the seed endophytic fungi of Corchorus olitorius through metabolomics and molecular docking approach.

BACKGROUND: Endophytic fungi are very rich sources of natural antibacterial and antifungal compounds. The main aim of this study is to isolate the fungal endophytes from the medicinal plant Corchorus olitorius seeds (F. Malvaceae), followed by antimicrobial screening against various bacterial and fungal strains. RESULTS: Seven endophytic fungal strains belonging to different three genera were isolated, including Penicillium, Fusarium, and Aspergillus. The seven isolated endophytic strains revealed selective noticeable activity against Escherichia coli (ATCC25922) with varied IC50s ranging from 1.19 to 10 µg /mL, in which Aspergillus sp. (Ar 6) exhibited the strongest potency against E. coli (ATCC 25,922) and candida albicans (ATCC 10,231) with IC50s 1.19 and 15 µg /mL, respectively. Therefore, the chemical profiling of Aspergillus sp. (Ar 6) crude extract was performed using LC-HR-ESI-MS and led to the dereplication of sixteen compounds of various classes (1-16). In-silico analysis of the dereplicated metabolites led to highlighting the compounds responsible for the antimicrobial activity of Aspergillus sp. extract. Moreover, molecular docking showed the potential targets of the metabolites; Astellatol (5), Aspergillipeptide A (10), and Emericellamide C (14) against E. coli and C. albicans. CONCLUSION: These results will expand the knowledge of endophytes and provide us with new approaches to face the global antibiotic resistance problem and the future production of undiscovered compounds different from the antibiotics classes.

Cytotoxic polyhydroxy sterols from the Egyptian Red Sea soft coral Sarcophyton acutum.

The methanolic extract and its sub-extracts (viz, n-hexane, DCM, EtOAc and MeOH) of the soft coral Sarcophyton acutum were evaluated as anti-Leishmania major and as anticancer (against the HepG2, MCF-7, and A549 cell lines) using the MTT assay. Six polyhydroxy sterols (1-6) were isolated from the most active cytotoxic and anti-leishmanial EtOAc-soluble fraction. Their structures were established as two new polyhydroxy sterols, acutumosterols A (1) and B (2), and four known structural analogues (3-6) by intensive spectroscopic analyses, and by comparison with data of related compounds. Compound 4 exerted noticeable cytotoxicity against HepG2 cell line (IC50 17.2 ± 1.5 µg/mL), while the other pure isolates showed weak to moderate cytotoxicity (24.8 ± 2.8-57.2 ± 5.2). The results were discussed in relation to the structural features of these closely related sterols.

Induction of Secondary Metabolites from the Marine-Derived Fungus Aspergillus versicolor through Co-cultivation with Bacillus subtilis.

A new cyclic pentapeptide, cotteslosin C (1: ), a new aflaquinolone, 22-epi-aflaquinolone B (3: ), and two new anthraquinones (9: and 10: ), along with thirty known compounds (2, 4:  - 8, 11:  - 34: ) were isolated from a co-culture of the sponge-associated fungus Aspergillus versicolor with Bacillus subtilis. The new metabolites were only detected in the co-culture extract, but not when the fungus was grown under axenic conditions. Furthermore, the co-culture extract exhibited an enhanced accumulation of the known constituents versicolorin B (14: ), averufin (16: ), and sterigmatocyctin (19: ) by factors of 1.5, 2.0, and 4.7, respectively, compared to the axenic fungal culture. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR spectra and mass spectrometry as well as by comparison with literature data. The absolute configuration of compounds 3, 9: , and 10: was determined by ECD (electronic circular dichroism) analysis aided by TDDFT-ECD (time-dependent density functional theory electronic circular dichroism) calculations. Compounds 15, 18:  - 21: , and 26: exhibited strong to moderate cytotoxic activity against the mouse lymphoma cell line L5178Y, with IC50 values ranging from 2.0 to 21.2 µM, while compounds 14, 16, 31, 32: , and 33: displayed moderate inhibitory activities against several gram-positive bacteria, with MIC values ranging from 12.5 to 50 µM.

Tanzawaic acid derivatives from freshwater sediment-derived fungus Penicillium sp.

Chemical investigation of a freshwater sediment-derived fungus, Penicillium sp. (S1a1), led to the isolation of three new tanzawaic acid derivatives, including penitanzchroman (1), tanzawaic acids Y (2) and Z (3), along with six known tanzawaic acid analogues (4-9), three known isochromans (10-12) and two known benzoquinones (13 and 14). The structures of the new compounds were established based on high-resolution mass spectrometry, and detailed analysis of one- and two-dimensional NMR spectroscopy. The relative configuration of the new compounds was assigned on the basis of NMR spectroscopic data including ROESY spectra. The absolute configuration was determined based on the specific optical rotation, in addition to biogenetic considerations in comparison with related co-isolated known metabolites. Penitanzchroman (1) constitutes a hitherto unprecedented skeleton, formed of tanzawaic acid A (5) and (3S)-6-hydroxy-8-methoxy-3,5-dimethylisochroman (10) linked by a CC bond. Moreover, all compounds were evaluated for their antibacterial and cytotoxic activities.

Aureobasidin, new antifouling metabolite from marine-derived fungus Aureobasidium sp.

Two antifouling compounds, aureobasidin (1), a new ester with an unusual 4,6-dihydroxydecanoic acid residue, and (3R,5S)-3,5-dihydroxydecanoic acid (2), were isolated from the marine-derived fungus Aureobasidium sp., in addition to (5R,3Z)-5-hydroxydec-3-enoic acid (3) and (R)-3-hydroxydecanoic acid (4). The structures were unambiguously established by IR, 1D and 2D NMR spectroscopic and mass spectral data. Compounds 1-3 were found to be active against Bacillus subtilis, Escherichia coli and Staphyllococcus aureus. Compound 3 showed fungistatic activity against Candida albicans.

Cesdiurins I-III, steroidal saponins from Cestrum diurnum L.

Phytochemical investigation of a methanolic extract of leaves of Cestrum diurnum L (Solanaceae) resulted in isolation of several furostanol steroidal saponins, named cesdiurins I-III (1-3). Their structures of the isolated compounds were determined by spectroscopic analyses, including by use of 1D and 2D NMR spectroscopic techniques as well as by mass spectral analyses.