The endophytic Aspergillus strains: A bountiful source of natural products.

Fungi that invade plant inner tissues without inducing disease symptoms are known as fungal endophytes. They represent a promising and tremendous reservoir of natural products with valuable biological potentials for application in medicine, agriculture and industry. Among the numerous existing endophytic fungi, Aspergillus strains constitute one of the most prolific sources of secondary metabolites with diverse chemical classes and interesting biological activities. This review covers the literature of the year 2020, reporting the isolation of 202 compounds obtained from more than 10 different endophytic Aspergillus species associated with different host plants. Analysis and interpretation of the collected data revealed that chemical investigation of endophytes belonging to the genus Aspergillus may greatly contribute to the discovery of potential drug leads. The isolated metabolites were chemically various and exhibited diverse biological activities such as antibacterial, anti-cancer, anti-plasmodial, anti-inflammatory, antioxidant, immunosuppressive and antifungal activities. Moreover, adoption of advanced technology in molecular biology together with modern chemical tools is anticipated to improve the discovery of new biopharmaceuticals from this valuable microbial world in the future.

New Cytotoxic Cerebrosides from the Red Sea Cucumber Holothuria spinifera Supported by In-Silico Studies.

Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC50 values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC50 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.

Antiproliferative activity of new pentacyclic triterpene and a saponin from Gladiolus segetum Ker-Gawl corms supported by molecular docking study.

A new triterpenoidal saponin identified as 3-O-[ß-d-glucopyranosyl-(1 → 2)-ß-d-glucopyranosyl-(1 → 4)-ß-d-xylopyranosyl]-2ß,3ß,16α-trihydroxyolean-12-en-23,28-dioic acid-28-O-α-l-rhamnopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl-(1 → 2)-α-l-arabinopyranoside 1 together with a new oleanane triterpene identified as 2ß,3ß,13α,22α-tetrahydroxy olean-23,28-dioic acid 2 and 6 known compounds (3-8) have been isolated from Gladiolus segetum Ker-Gawl corms. The structural elucidation of the isolated compounds was confirmed using different chemical and spectroscopic methods, including 1D and 2D NMR experiments as well as HR-ESI-MS. Moreover, the in vitro cytotoxic activity of the fractions and that of the isolated compounds 1-8 were investigated against five human cancer cell lines (PC-3, A-549, HePG-2, MCF-7 and HCT-116) using doxorubicin as a reference drug. The results showed that the saponin fraction exhibited potent in vitro cytotoxic activity against the five human cancer cell lines, whereas the maximum activity was exhibited against the PC-3 and A-549 cell lines with the IC50 values of 1.13 and 1.98 µg mL-1, respectively. In addition, compound 1 exhibited potent activity against A-549 and PC-3 with the IC50 values of 2.41 µg mL-1 and 3.45 µg mL-1, respectively. Interestingly, compound 2 showed the maximum activity against PC-3 with an IC50 of 2.01 µg mL-1. These biological results were in harmony with that of the molecular modeling study, which showed that the cytotoxic activity of compound 2 might occur through the inhibition of the HER-2 enzyme.

Inhibition of SARS-CoV-2 main protease by phenolic compounds from Manilkara hexandra (Roxb.) Dubard assisted by metabolite profiling and in silico virtual screening.

SARS-CoV-2 is a novel coronavirus that was first identified during the outbreak in Wuhan, China in 2019. It is an acute respiratory illness that can transfer among human beings. Natural products can provide a rich resource for novel antiviral drugs. They can interfere with viral proteins such as viral proteases, polymerases, and entry proteins. Several naturally occurring flavonoids were reported to have antiviral activity against different types of RNA and DNA viruses. A methanolic extract of Manilkara hexandra (Roxb.) Dubard leaves is rich in phenolic compounds, mainly flavonoids. Metabolic profiling of the secondary metabolites of Manilkara hexandra (Roxb.) Dubard leaves methanolic extract (MLME), and bark ethyl acetate (MBEE) extract using LC-HRESIMS resulted in the isolation of 18 compounds belonging to a variety of constituents, among which phenolic compounds, flavones, flavonol glycosides and triterpenes were predominant. Besides, four compounds (I-IV) were isolated and identified as myricetin I, myricitrin II, mearnsitrin III, and mearnsetin-3-O-ß-d-rutinoside IV (compound IV is isolated for the first time from genus Manilkara) and dereplicated in a metabolomic study as compounds 3, 5, 6, and 12, respectively. The molecular docking study showed that rutin, myricitrin, mearnsitrin, and quercetin 3-O-ß-d-glucoside have strong interaction with SARS-CoV-2 protease with high binding energy of -8.2072, -7.1973, -7.5855, and -7.6750, respectively. Interestingly, the results proved that rutin which is a citrus flavonoid glycoside exhibits the strongest inhibition effect to the SARS-CoV-2 protease enzyme. Consequently, it can contribute to developing an effective antiviral drug lead against the SARS-CoV-2 pandemic.

Xanthone and lignan glycosides from the aerial parts of Polygonum bellardii all growing in Egypt.

A new long chain fatty alcohol acetate identified as 17-hydroxypentacosanyl acetate, (1) together with a new xanthone identified as 1,8-Dihydroxy-3,6-dimethoxy-xanthone-5-O-[α-L-rhamnopyranosyl-(1''→2')]-ß-D-glucopyranoside (3), as well as two new lignans identified as (+)-Lyoniresinol-3a-O-[α-L-rhamnopyranosyl-(1'''→6'')]-ß-D-glucopyranoside (4) and (+)-Isolariciresinol-3a-O-[α-L-rhamnopyranosyl-(1'''→2'')-α-L-rhamnopyranosyl-(1''''→6'')]-ß-D-glucopyranoside (5), in addition to ß-sitosterol-3-O-acetate (2) were isolated from the methanolic extract of the aerial parts of Polygonum bellardii growing in Egypt. Their structures were elucidated on the basis of different chemical and spectroscopic evidences. The total extract and its fractions, in addition to compounds (3, 4 and 5) showed significant antioxidant potential by DPPH(·) scavenging activity technique.