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This work was performed to dig into the phytochemical composition and bioactivities of Nocardiopsis sp. UR67 associated with the marine sponge Callyspongia sp. It was fermented in suspension and immobilised in calcium alginate bead cultures. The ethyl acetate extracts, afforded from the broth in each case named EG-49 and J-48g, respectively, revealed 16 chemical principles mostly belonging to polyketides, macrolides, and peptides. EG-49 and J-48g displayed anti-Candida albicans activity with IC50 values of 8.1 and 8.3 µg/mL, and a substantial cytotoxic effect against lung adenocarcinoma H1650 at IC50 12.6 and 13.7 µg/mL, respectively. However, only EG-49 exhibited a noteworthy anti-trypanosomal activity at 7.5 µg/mL. Molecular docking of the characterised compounds against Trypanosoma brucei trypanothione reductase demonstrated the highest binding models of griseochelin-methyl ester (9) and filipin-II (11), which drew considerable significance of the metabolites derived from Nocardiopsis sp. UR67 developing potential T. brucei trypanothione reductase inhibitors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Chelonaplysilla genus possesses a numerous bioactive diterpenes with anti-inflammatory and cytotoxic effects. The current study aimed to assess the chemical composition of C. erecta crude extract (CECE) based on its metabolomic profile that has been integrated with neural network-based virtual screening and molecular docking using liquid chromatography with high resolution mass spectrometry (LCHR-MS). In addition to the estimation of the antitumor activity of the same extract via anti-interleukin-17A (IL-17) action, along with its formulated spanlastics preparation. The CECE markedly displayed growth inhibition for HepG-2 cells at IC50 value 16.5 ± 0.8 μg/mL, whereas the spanlastic formulation revealed more eminent antitumor effect against Caco-2 cells (IC50 = 2.8 ± 0.03 μg/mL). Among the dereplicated compounds, macfarlandin F (16) and pourewanone (25) demonstrated the highest potential with co-crystallized ligand 63 O within the active site of IL-17A in molecular docking studies. These findings rationalized the antitumor mechanism of marine organism for future chemotherapeutic applications. [ABSTRACT FROM AUTHOR]

The continuous impedance of Pseudomonas aeruginosa to traditional antibacterial drugs due to biofilm formation resulted in a growing necessity to develop effective antibiofilm formation treatments. Thus, such a study was conducted to search for the natural metabolites from the endophytic Penicillium chrysoginum AJEF2 as a source of prospective antibiofilm-forming agents. Generally, the OSMAC (one strain many compounds) approach was undertaken to ascertain that the modified potato dextrose broth (MPDB) culture displayed substantial antibacterial potential towards various human pathogenic microorganisms (MICs = 125–500 µg/mL) and exhibited a remarkable percentage of biofilm inhibition against Pseudomonas aeruginosa clinical isolates by 92.3%. LC-ESI-HRMS analysis of such extract annotated seventeen metabolites that were screened for their inhibitory biofilm formation based on molecular docking simulation on LasR protein-specific quorum sensing. Interestingly, gladiolic acid, 8‑hydroxy-6-methylxanthone-1-carboxylic acid methyl ester, cyclo(L-tryptophanyl- l -tryptophanyl), and citreoanthrasteroid A, showed acceptable interaction energies and formed significant interactions inside the LasR active site. Those results highlight endophytic Penicillium chrysoginum AJEF2 as a potential source for antibiofilm compounds. [Display omitted] • Antimicrobial and anti-biofilm forming activities were displayed by the endophytic P. chrysogenum AJEF2 strain isolated from Artemisia judica. • LC HRMS analysis characterized structurally assorted metabolites, mainly phenolics, benzopyran, benzofuran, coumarins, polyketide, dipeptide, meroterpene, and steroids. • Molecular docking simulation on LasR protein-specific quorum sensing was done. • Gladiolic acid, 8‑hydroxy-6-methylxanthone-1-carboxylic acid methyl ester, cyclo(L-tryptophanyl- l -tryptophanyl) and citreoanthrasteroid A, were the most likely to inhibit the biofilm formation based on molecular docking studies. [ABSTRACT FROM AUTHOR]

Ethanol extracts of Caulerpa racemose, Halimeda opuntia, Padina pavonica, Polycladia myrica, and Turbinaria ornata were tested for anti-Hepatitis C virus activity. H. opuntia ethanol extract exhibited activity against hepatitis C virus (HCV) with IC 50 value of 7.14 µg/mL. LC HR-ESI-MS metabolite profiling of H. opuntia ethanol extract characterized fifteen metabolites, which were screened for their polymerase inhibitory (HCV-796) binding sites based on molecular docking simulation. Interestingly 4,9-diacetoxtudoteal showed good interaction energies and formed significant interactions with the HCV-796 binding site. [Display omitted] Ø Ethanol extracts of Caulerpa racemose, Halimeda opuntia, Padina pavonica, Polycladia myrica , and Turbinaria ornata were tested for anti-Hepatitis C virus activity. Ø H. opuntia ethanol extract has anti-HCV activity, IC 50 = 7.14 µg/mL. LC HR-ESI-MS metabolic profiling of H. opuntia ethanol extract characterized fifteen metabolites. Ø The inhibitory HCV-796 binding site in the HCV polymerase based on molecular docking simulation on the HCV binding site in the HCV polymerase were detected. Ø Interestingly 4,9-diacetoxtudoteal showed good interaction energies and formed significant interactions with the HCV-796 binding site. [ABSTRACT FROM AUTHOR]

The current biologically guided study aimed the in vitro investigation of cytotoxic activity, identification of the phytochemical content of Moluccella laevis L. aerial parts and supporting this activity by a molecular docking study. Aqueous fraction demonstrated the most potent cytotoxic effect against CACO-2 with IC50 = 0.067 ± 0.01 μg/mL. Furthermore, EtOAc fraction showed a remarkable cytotoxic activity against MCF-7 cell line with IC50 = 0.35 ± 0.02 μg/mL. Consequently, total ethanolic extract (TEE) and its fractions were subjected to LC-HR-ESI-MS metabolic profiling to discover the constituents that possibly underlie their cytotoxicity. Twenty compounds were tentatively identified from metabolic analysis. Furthermore, eight compounds were isolated. In silico docking study revealed that stachydrine is more likely to account for the antiproliferative activity of both EtOAc and aqueous fractions, probably via its moderate inhibition of receptor tyrosine kinases. [ABSTRACT FROM AUTHOR]

• The chemical composition of Amphilophium paniculatum (L.) leaves was investigated. • Many structurally varied metabolites were identified for the first time in the genus. • Various metabolites from this underexplored species showed key chemotaxonomic value. • The binding ability of A. paniculatum compounds to SARS-CoV-2 Mpro was explored. • The docked flavonoids, phenylethanoids, and lignans showed the highest binding to Mpro. Bignoniaceae plants are multipurpose herbal remedies with privileged chemical and biological profiles; nevertheless, some members in this family, e.g. Amphilophium species, have been scarcely investigated. Therefore, this work explores the chemical complexity of the underexplored species, Amphilophium paniculatum (L.) Kunth as a potential source of inhibitory phytochemicals against the recently emerging coronavirus disease (COVID-19). Overall, 13 structurally varied metabolites were isolated from the ethyl acetate and n -butanol fractions of A. paniculatum leaves for the first time in the genus and identified by different spectral techniques, including 1H and 13C NMR, DEPT, and HR–ESI–MS analyses. The characterized compounds (1–13) , along with those previously obtained by our group from the same species (14–22) revealed varying binding affinities to the active site of SARS-CoV-2 Mpro, among which, eight molecules exhibited lower binding energies (–9.54 to –7.45 kcal/mol) than the ligand N3 (–7.44 kcal/mol); with polyphenolic metabolites, namely flavonoids, phenylethanoids, and lignans had the most stable interactions, respectively. These results highlighted the noteworthy diversity of A. paniculatum metabolites and their marked homogeneity with those produced by other Bignoniaceae plants, which would help expand our phytochemical and chemotaxonomic knowledge on this species. Coupling such phytochemical data with molecular docking studies could also allow a time- and cost-effective search for potential anti-COVID-19 agents. [ABSTRACT FROM AUTHOR]

Chemical profiles of total alcohol extract and various derived fractions of aerial parts of Zinnia elegans were studied. Accordingly, eight flavonoids were isolated from the ethyl acetate derived fraction based on the antioxidant assay-guided purification, using DPPH and phosphomolybdate complex assays. Eventually, the binding affinities and features of the eight isolated flavonoids were investigated using the molecular docking technique towards SARS-CoV-2 and human targets –namely main protease (Mpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), receptor-binding domain (RBD), helicase (NSP13), human angiotensin‐converting enzyme 2 (ACE2), and human neuropilin-1 (NRP1). Docking calculations unveiled the surpass binding affinity of glabrisoflavone with Mpro, PLpro, RdRp, RBD, NSP13, ACE2, and NRP1, with docking scores of −9.2, −7.4, −6.9, −6.9, −8.5, −9.0, and −7.6 kcal/mol, respectively. Binding mode analysis manifested the capability of glabrisoflavone to form several hydrogen bonds with the key amino acid residues inside the active sites of the targets. Besides, 25 ns molecular dynamics (MD) simulations combined with molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations were executed to inspect the binding affinity of glabrisoflavone and compared to an anti-HIV-1 protease inhibitor (darunavir). MM-GBSA calculations demonstrated greater glabrisoflavone affinity for the PLpro, RdRp, RBD and NRP1 over darunavir. Nevertheless, MM-GBSA calculations displayed equal or lower glabrisoflavone affinity against Mpro, NSP13 and ACE2 compared to darunavir. The current study obviously emphasizes the fitness of the glabrisoflavone as an auspicious clinical drug candidate for further development and future in vivo and in vitro evaluations towards viral targets and human targets. [Display omitted] • Eight flavonoids were isolated from Erythrina suberosa is a medicinal plant known aerial parts of Zinnia elegans. • Various fractions of plant are screened for antioxidant activity. • The isolated flavonoids were subjected to molecular docking studies towards SARS-CoV-2. [ABSTRACT FROM AUTHOR]