Browsing by Author "Abdelmohsen, Usama Ramadan"

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Chemical and biological studies on the soft coral Nephthea sp
(Royal Society of Chemistry, 2021-06) Abdelhafez, Omnia Hesham; Fahim, John Refaat; El Masri, Ramy R.; Salem, M. Alaraby; Desoukey, Samar Yehia; Ahmed, Safwat; Kamel, Mohamed Salah; Pimentel-Elardo, Sheila Marie; Nodwell, Justin R; Abdelmohsen, Usama Ramadan
Soft corals belonging to the family Nephtheidae have been appreciated as marine sources of diverse metabolites with promising anticancer potential. In view of that, the current work investigates the anti- proliferative potential of the crude extract, different fractions, and green synthesized silver nanoparticles (AgNPs) of the Red Sea soft coral, Nephthea sp. against a panel of tumor cell lines. The metabolic pool of the soft coral under study was also explored via an LC-HR-ESI-MS metabolomics approach, followed by molecular docking analysis of the characterized metabolites against the target proteins, EGFR, VEGFR, and HER2 (erbB2) that are known to be involved in cancer cell proliferation, growth, and survival. Overall, the n- butanol fraction of Nephthea sp. exhibited the highest inhibitory activities against MCF7 (breast cancer) and A549 (lung cancer) cell lines, with interesting IC50 values of 2.30 0.07 and 3.12 0.10 mg ml 1 , respectively, whereas the maximum growth inhibition of HL60 (leukemia) cells was recorded by the total extract (IC50 ¼ 2.78 0.09 mg ml 1 ). More interestingly, the anti-proliferative potential of the total soft coral extract was evidently improved when packaged in the form of biogenic AgNPs, particularly against A549 and MCF7 tumor cells, showing IC50 values of 0.72 0.06 and 9.32 0.57 mg ml 1 , respectively. On the other hand, metabolic profiling of Nephthea sp. resulted in the annotation of structurally diverse terpenoids, some of which displayed considerable binding affinities and molecular interactions with the studied target proteins, suggesting their possible contribution to the anti-proliferative properties of Nephthea sp. via inhibition of tyrosine kinases, especially the EGFR type. Taken together, the present findings highlighted the relevance of Nephthea sp. to future anticancer drug discovery and provided a base for further work on the green synthesis of a range of bioactive NPs from marine soft corals.
Chemical and biological studies on the soft coral Nephthea sp.
(Royal Society of Chemistry, 2021-06) Abdelhafez, Omnia Hesham; Fahim, John Refaat; El Masri, Ramy R; Salem, M. Alaraby; Desoukey, Samar Yehia; Ahmed, Safwat; Kamel, Mohamed Salah; Pimentel-Elardo, Sheila Marie; Nodwell, Justin R; Abdelmohsen, Usama Ramadan
Soft corals belonging to the family Nephtheidae have been appreciated as marine sources of diverse metabolites with promising anticancer potential. In view of that, the current work investigates the anti- proliferative potential of the crude extract, different fractions, and green synthesized silver nanoparticles (AgNPs) of the Red Sea soft coral, Nephthea sp. against a panel of tumor cell lines. The metabolic pool of the soft coral under study was also explored via an LC-HR-ESI-MS metabolomics approach, followed by molecular docking analysis of the characterized metabolites against the target proteins, EGFR, VEGFR, and HER2 (erbB2) that are known to be involved in cancer cell proliferation, growth, and survival. Overall, the n- butanol fraction of Nephthea sp. exhibited the highest inhibitory activities against MCF7 (breast cancer) and A549 (lung cancer) cell lines, with interesting IC50 values of 2.30 0.07 and 3.12 0.10 mg ml 1 , respectively, whereas the maximum growth inhibition of HL60 (leukemia) cells was recorded by the total extract (IC50 ¼ 2.78 0.09 mg ml 1 ). More interestingly, the anti-proliferative potential of the total soft coral extract was evidently improved when packaged in the form of biogenic AgNPs, particularly against A549 and MCF7 tumor cells, showing IC50 values of 0.72 0.06 and 9.32 0.57 mg ml 1 , respectively. On the other hand, metabolic profiling of Nephthea sp. resulted in the annotation of structurally diverse terpenoids, some of which displayed considerable binding affinities and molecular interactions with the studied target proteins, suggesting their possible contribution to the anti-proliferative properties of Nephthea sp. via inhibition of tyrosine kinases, especially the EGFR type. Taken together, the present findings highlighted the relevance of Nephthea sp. to future anticancer drug discovery and provided a base for further work on the green synthesis of a range of bioactive NPs from marine soft corals.
Dereplication Analysis and Antitrypanosomal Potential of the Red Sea Sponge Amphimedon sp. Supported by Molecular Modelling
(Springer, 2020-03) Hisham Shady, Nourhan; Elfakharany, Zeinab; Salem, M. Alaraby; Ahmed, Safwat; Fouad, Mostafa A.; Salah Kamel, Mohamed; Krischke, Markus; Mueller, Martin J.; Abdelmohsen, Usama Ramadan
The present investigation was oriented to the discovery of chemical compounds from the Red Sea sponge Amphimedon sp., as a source of active agents against Trypanosoma brucei, the causal agent of human sleeping sickness. Dereplication analysis of the active fraction from Amphimedon sp. using liquid chromatography coupled with high-resolution mass spectrometry revealed the chemical richness of this sponge with diverse alkaloidal classes such as purine, manzamine, bis-piperidine, and pyridine. Activity-guided fractionation of the total extract showed the antitrypanosomal activity concentrated in the ethyl acetate fraction (IC50 = 3.8 μg/ml). In silico modelling was carried out on the dereplicated compounds to provide an insight into their antitrypanosomal mechanism of action with docking study on eight trypanosomal proteins. Molecular dynamics was run for the complex of zamamidine D and ornithine decarboxylase, which illustrated that zamamidine D has the highest affinity to the ornithine decarboxylase enzyme. These results highlight the valuable chemical profile of Amphimedon sp., as a lead source for antitrypanosomal natural products.
Increment of Lysosomal Biogenesis by Combined Extracts of Gum Arabic, Parsley, and Corn Silk: A Reparative Mechanism in Mice Renal Cells
(Hindawi, 07/11/2020) Helmy, Aya; El-Shazly, Mohamed; Omar, Nesreen; Rabeh, Mohamed; Abdelmohsen, Usama Ramadan; Tash, Reham; Salem, Mohammad Alaraby; Samir, Ahmed; Elshamy, Ali; Singab, Abdel Nasser B.
Gum Arabic (GA), parsley, and corn silk have been traditionally used for renal failure patients worldwide. This study aimed at probing the mechanism of the combined extracts, namely, GA (3 g/kg/day), parsley (1 g/kg/day), and corn silk (200 mg/kg/day), as nephroprotective agents in mice after amikacin (1.2 g/kg) single dose through exploration of their action on G-protein coupled receptors (GPR) 41 and 43 and the ensuing lysosomal biogenesis. Western blotting was employed for renal levels of bcl-2-associated X protein (BAX) and cytosolic cathepsin D; cell death markers, nuclear transcription factor EB (TFEB), and lysosomal associated membrane protein-1 (LAMP-1); and lysosomal biogenesis indicators. Liquid chromatography–mass spectrometry (LC-MS) and docking were also employed. After amikacin treatment, BAX and cathepsin D levels were upregulated while LAMP-1 and nuclear TFEB levels were inhibited. The combined extracts inhibited BAX and cytosolic cathepsin D but upregulated LAMP-1 and nuclear TFEB levels. Docking confirmed GPR modulatory signaling. The combined extracts showed GPR signal modulatory properties that triggered lysosome synthesis and contributed to reversing the adverse effects of amikacin on renal tissues.
The metabolomic analysis of five Mentha species: cytotoxicity, anti-Helicobacter assessment, and the development of polymeric micelles for enhancing the anti-Helicobacter activity
(Royal Society of chemistry, 1/13/2021) Bakr, Riham O; Tawfike, Ahmed; El-Gizawy, Heba A; Tawfik, Nashwa; Abdelmohsen, Usama Ramadan; Abdelwahab, Miada F.; Alshareef, Walaa A; Fayez, Sahar M.; El-Mancy, Shereen M. S; El-Fishawy, Ahlam M; Abdelkawy, Mostafa A; Fayed, Marwa A. A
Mentha species are medicinally used worldwide and remain attractive for research due to the diversity of their phytoconstituents and large therapeutic indices for various ailments. This study used the metabolomics examination of five Mentha species (M. suaveolens, M. sylvestris, M. piperita, M. longifolia, and M. viridis) to justify their cytotoxicity and their anti-Helicobacter effects. The activities of species were correlated with their phytochemical profiles by orthogonal partial least square discriminant analysis (OPLS-DA). Tentatively characterized phytoconstituents using liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) included 49 compounds: 14 flavonoids, 10 caffeic acid esters, 7 phenolic acids, and other constituents. M. piperita showed the highest cytotoxicity to HepG2 (human hepatoma), MCF-7 (human breast adenocarcinoma), and CACO2 (human colon adenocarcinoma) cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. OPLS-DA and dereplication studies predicted that the cytotoxic activity was related to benzyl glucopyranoside-sulfate, a lignin glycoside. Furthermore, M. viridis was effective in suppressing the growth of Helicobacter pylori at a concentration of 50 mg mL1. OPLS-DA predicted that this activity was related to a dihydroxytrimethoxyflavone. M. viridis extract was formulated with Pluronic® F127 to develop polymeric micelles as a nanocarrier that enhanced the anti-Helicobacter activity of the extract and provided minimum inhibitory concentrations and minimum bactericidal concentrations of 6.5 and 50 mg mL1, respectively. This activity was also correlated to tentatively identified constituents, including rosmarinic acid, catechins, carvone, and piperitone oxide.
Multitarget in silico studies of Ocimum menthiifolium, family Lamiaceae against SARS-CoV-2 supported by molecular dynamics simulation
(Taylor and Francis, 2020-12) Zahran, Eman Maher; Fouad, Mostafa A.; Abdelmohsen, Usama Ramadan; Kamel, Mohamed S; Khalil, Hany Ezzat; Desoukey, Samar Yehia; Salem, Mohammad Alaraby
The novel strain of human coronavirus, emerged in December 2019, which has been designated as SARS-CoV-2, causes a severe acute respiratory syndrome. Since then, it has arisen as a serious threat to the world public health. Since no approved vaccines or drugs has been found to efficiently stop the virulent spread of the virus, progressive inquiries targeting these viruses are urgently needed, especially those from plant sources. Metabolic profiling using LC-HR-ESI-MS of the butanol extract of Ocimum menthiifolium (Lamiaceae) aerial parts yielded 10 compounds including flavonoids, iridoids and phenolics. As it has been previously reported that some flavonoids can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose to examine 14 flavonoids (detected by metabolomics and other compounds isolated via several chromatographic techniques). We investigated their potential binding interactions with the 4 main SARS-CoV-2 targets: Mpro, nsp16/nsp10 complex, ACE2-PD and RBD-S-protein via molecular docking. Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with 9.4, 9.3 and 9.3kcal/mol binding energy, respectively, compared to the control (SAM) with 8.2kcal/mol. Furthermore, the stability of these complexes was studied using molecular dynamics of 150ns, which were then compared to their complexes in the other three targets. MM-PBSA calculations suggested the high stability of acaciin-nsp16 complex with binding energy of 110kJ/mol. This study sheds light on the structure-based design of natural flavonoids as antiSARS-CoV-2 drugs targeting the nsp16/10 complex. Abbreviations: ACE2-PD: Angiotensin converting enzyme 2 protease domain; ARDS: Acute respiratory distress syndrome; COVID-19: Corona virus disease; Mpro: Main protease; MD: Molecular dynamics; PDB: Protein data bank; RBD-S: Receptor binding domain; RMSD: Root mean square deviation; SAM: Sadenosylmethionine; SARS: Severe acute respiratory syndrome