Terretonin N: A New Meroterpenoid from Nocardiopsis sp.

Hamed A, Abdel-Razek AS, Frese M, et al. Terretonin N: A New Meroterpenoid from Nocardiopsis sp. Molecules. 2018;23(2): 299.Terretonin N (1), a new highly oxygenated and unique tetracyclic 6-hydroxymeroterpenoid, was isolated together with seven known compounds from the ethyl acetate extract of a solid-state fermented culture of Nocardiopsis sp. Their structures were elucidated by spectroscopic analysis. The structure and absolute configuration of 1 were unambiguously determined by X-ray crystallography. The isolation and taxonomic characterization of Nocardiopsis sp. is reported. The antimicrobial activity and cytotoxicity of the strain extract and compound 1 were studied using different microorganisms and a cervix carcinoma cell line, respectively

Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla.

Kaaniche F, Hamed A, Abdel-Razek AS, et al. Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla. PLoS ONE. 2019;14(6): E0217627.Over the last decades, endophytic fungi represent a new source of pharmacologically active secondary metabolites based on the underlying assumption that they live symbiotically within their plant host. In the present study, a new endophytic fungus was isolated from Rauwolfia macrophylla, a medicinal plant from Cameroon. The fungus showed a highest homology to Curvularia sp. based on complete nucleotide sequence data generated from the internal transcribed spacer (ITS) of ribosomal DNA region. Large scale fermentation, working-up and separation of the strain extract using different chromatographic techniques afforded three bioactive compounds: 2'-deoxyribolactone (1), hexylitaconic acid (2) and ergosterol (3). The chemical structures of compounds 1-3 were confirmed by 1 and 2D NMR spectroscopy and mass spectrometry, and comparison with corresponding literature data. Biologically, the antimicrobial, antioxidant activities and the acetylcholinesterase inhibitory of the isolated compounds were studied

Penicisteroid C: New polyoxygenated steroid produced by co-culturing of Streptomyces piomogenus with Aspergillus niger

Abdel-Razek AS, Hamed A, Frese M, Sewald N, Shaaban M. Penicisteroid C: New polyoxygenated steroid produced by co-culturing of Streptomyces piomogenus with Aspergillus niger. Steroids. 2018;138:21-25.Penicisteroid C, a new polyoxygenated steroid was isolated from co-cultivation of Streptomyces piomogenus AS63D and Aspergillus niger using solid-state fermentation on rice medium. Additional diverse eleven known metabolites were identified: Fumigaclavine C, fumiquinazoline C, physcion, methylsulochrin, methyllinoleate, glycerol linoleate, cerebroside A, thymine, adenine, thymidine and adenosine. The structure of penicisteroid C was determined by HRESIMS, 1D and 2D NMR data. The antimicrobial and in vitro cytotoxic activities of the microbial extract and penicisteroid C were reported as well

Ecological and Phytochemical Studies on Euphorbia retusa (Forssk.) from Egyptian Habitat

This study deals with the ecology, phytochemistry, and biological activity investigation of Euphorbia retusa, belonging to Euphorbiaceae family, obtained from Egypt. Ecologically, Euphorbia retusa secretes white sap inhibiting the growth of the other species, so Euphorbia retusa is forming complete patches. Phytochemical study of the plant was visualized intensively based on its extraction with a protic organic solvent, working up and purifying its entire bioactive compounds using a series of different chromatographic techniques. A broad range of diverse compounds were isolated, namely, 1-hexacosanol (1), 3β-hydroxy-24-methylene-9,19-cyclolanostane; 24-methylenecycloartanol (2), 3β-hydroxy-9,19-cyclolanostane; cyclolaudanol (3), 3β,24S-Ergost-5-en-ol (4), and methyllinoleate. Additionally, GC-MS analysis of the unpolar fractions detected the existence of n-dodecane, methyllaurate, 6,10,14-trimethyl-pentadecan-2-one (5), 6,10-dimethyl-undecan-2-one (6), 2-methyl-hexadecanal (7), methylpalmitate, methyl-9,12,15-octadecatrienoate (8), and n-heneicosane (9). A full assignment for compounds 2 and 3 using 1 and 2 DNMR was carried out herein for the first time. The antimicrobial activity of the strain extract and obtained compounds was studied using a panel of pathogenic bacterial strains. The in vitro cytotoxicity of the compounds as well as the crude extract was studied against the human cervix carcinoma cell line (KB-3-1)

Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II

Hamed A, Abdelwahab AB, Soltan MM, Stammler H-G, Shaaban M. Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II. Journal of Molecular Structure . 2022;1258: 132655.Butyrolactone I is a natural butenolide that has been isolated from the culture broth of the thermophilic fungus Aspergillus terreus TM8. Its structure was determined by HR-ESI-MS as well as NMR spectroscopic data. The crystal structure and absolute configuration of butyrolactone I are reported herein for the first time based on single crystal X-ray diffraction. Butyrolactone I is known as a highly selective inhibitor of cyclin-dependent protein kinases which inhibits cell cycle progression at the G(1)/S and G(2)/M transitions. Through this study, we investigate the action of butyrolactone I against the human topoisomerase II (topo II) and vascular endothelial growth factor receptor2 (VEGFR2) kinase. The molecular docking results introduced butyrolactone I either as a catalytic inhibitor against topo II alpha or a poison to topo II beta while the first mechanism is the most likely to take place. Contrarily to topo II, butyrolactone I displayed a low affinity toward VEGFR2 kinase. In the light of the molecular docking investigation, butyrolactone I, in synchronizing to a catalytic inhibitor and poison control, was subjected to the in vitro topo II alpha relaxation assay. The results revealed the capability of butyrolactone I to suppress the relaxation of the supercoiled DNA plasmid in a concentration-dependent manner, with IC50 value of 6.64 mu M. Interestingly, this IC50 was more comparable to the catalytic inhibitor (staurosporine) rather than the poison one (doxorubicin). (c) 2022 Elsevier B.V. All rights reserved.& nbsp

Synthesis of novel feruloyl dipeptides with proapoptotic potential against different cancer cell lines.

Hamed A, Frese M, Elgaafary M, et al. Synthesis of novel feruloyl dipeptides with proapoptotic potential against different cancer cell lines. Bioorganic chemistry. 2020;97: 103678.In this study, a series of novel N-feruloyl dipeptides (10-17) have been synthesized through the coupling of N-feruloyl amino acids (6-9) with glycine/alanine methyl ester hydrochloride. Structures of the peptides were assigned using 1D and 2D NMR and HRESIMS. According to initial in vitro cytotoxic screening against the cervix carcinoma cell line KB-3-1, aromatic dipeptides (12, 13, 16, 17) were the most potent ones among all tested feruloyl dipeptides. Accordingly, these peptides were further intensively investigated as potential anticancer agents against a panel of ten cancer cell lines from different tissue origin. Based on that, compound 17 showed the strongest cytotoxic efficiency towards the whole panel of tested cell lines with IC50 values from 2.1 to 7.9muM. By contrast, the dipeptides 12, 13 and 16 showed moderate to weak cytotoxicity (IC50 16.1-28.3 or >30, 5.7-21.9 and 3.9-21.2 or ≥30muM, respectively). Mechanistically, compound 17 induced a strong dissipation of the mitochondrial transmembrane potential and an early activation of caspase 3/7 in the triple-negative MDA-MB-231 breast cancer cell line. In an in vivo model, compound 17 inhibited growth, proliferation and induced apoptosis in MDA-MB-231 xenografted onto the chick chorioallantoic membrane. All the synthesized compounds were also tested against a set of pathogenic bacterial strains, displaying no potential activity. Copyright © 2020 Elsevier Inc. All rights reserved

Coumamarin: a first coumarinyl calcium complex isolated from nature.

Hamed A, Abdel-Razek AS, Frese M, et al. Coumamarin: a first coumarinyl calcium complex isolated from nature. Journal of antibiotics. 2019;72(10):729-735.The first calcium complex from nature, Coumamarin (1), 7-hydroxy-3-methoxy-2-oxo-2H-chromene-6-carboxylate Ca(II) complex, was isolated from Aspergillus sydowii ASTI, together with diorcinol (2), violaceol I (3), hydroxysydonic acid (4), cyclo (Trp-Phe), kojic acid, ergosterol, and uracil. The producing strain was isolated from marine water sample collected from Tiran Island, Red Sea, Egypt. Structure 1 was assigned by intensive 1D, 2D NMR, HR-ESIMS, and X-ray crystallography as well. Coumamarin is potentially active against certain tested bacteria and yeasts, while showing no cytotoxic activity against human cervix carcinoma cell line (KB-3-1). Taxonomically, the fungus was identified by phylogenetic analysis of its 18S rRNA gene sequence

Diverse Bioactive Secondary Metabolites from Aspergillus terreus: Antimicrobial, Anticancer and Anti- SARS-CoV-2 Activity Studies

Hamed A, Abdel-Razek AS, Abdelwahab AHMEDB, et al. Diverse Bioactive Secondary Metabolites from Aspergillus terreus: Antimicrobial, Anticancer and Anti- SARS-CoV-2 Activity Studies. 2023.The recently reported microbial natural product N-benzoyl-tryptophane (1) along with twenty-two diverse known bioactive compounds were isolated from the marine Aspergillus terreus LGO13 after its re-cultivation using liquid culture fermentation. Structures of the isolated compounds were established on the basis of HR-ESIMS 1D/2D NMR spectroscopy, and comparison with literature data. The antimicrobial, cytotoxicity, and antiviral activities of the microbial extract and the obtained compounds were investigated using a set of microorganisms, cervix carcinoma KB-3-1, non-small cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulation was employed to explore the theoretical targets of the isolated metabolites as anti-SARS-CoV-2 agents. Chaetominine (2) seemed to be a potential candidate against papain-like protease (PLpro), one of the viral proteins being aimed by recent research as a possible target of anti-covid agents. Inspired by the MD results, we accordingly assessed the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2. Fumitremorgin C (6) showed a high selectivity index (SI = 20.3), while chaetominine (2) and azaspirofuran A (9) showed moderate selectivity index (SI = 6.6 and 3.2, respectively). These results showed a promising antiviral activity of Fumitremorgin C against SARS-CoV-2 virus

Thiazolidinedione Derivatives: In Silico, In Vitro, In Vivo, Antioxidant and Anti-Diabetic Evaluation

This work aimed to synthesize a new antihyperglycemic thiazolidinedione based on the spectral data. The DFTB3LYP6-311G** level of theory was used to investigate the frontier molecular orbitals (FMOs), chemical reactivity and map the molecular electrostatic potentials (MEPs) to explain how the synthesized compounds interacted with the receptor. The molecular docking simulations into the active sites of PPAR-γ and α-amylase were performed. The in vitro potency of these compounds via α-amylase and radical scavenging were evaluated. The data revealed that compounds (4–6) have higher potency than the reference drugs. The anti-diabetic and anti-hyperlipidemic activities for thiazolidine-2,4-dione have been investigated in vivo using the alloxan-induced diabetic rat model along with the 30 days of treatment protocol. The investigated compounds didn’t show obvious reduction of blood glucose during pre-treatments compared to diabetic control, while after 30 days of treatments, the blood glucose level was lower than that of the diabetic control. Compounds (4–7) were able to regulate hyperlipidemia levels (cholesterol, triglyceride, high-density lipoproteins and low- and very-low-density lipoproteins) to nearly normal value at the 30th day

Crystal structure and configuration revision of 9-hydroxy-7,8-dehydro-sarcotrocheliol and sarcotrocheliol

Hamed A, Issa MY, Ghani MA, et al. Crystal structure and configuration revision of 9-hydroxy-7,8-dehydro-sarcotrocheliol and sarcotrocheliol . Natural product research. 2019;33(20):3029-3032