Publications

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2022
El Gaafary, M., F. R. Saber, E. A. Mahrous, R. M. Ashour, M. O. N. A. M. OKBA, L. Jin, S. J. Lang, M. Schmiech, T. Simmet, and T. Syrovets, "The phloroglucinol calcitrinone A, a novel mitochondria-targeting agent, induces cell death in breast cancer cells", Food and Chemical Toxicology, vol. 162: Elsevier, pp. 112896, 2022. Abstract
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2021
El Gaafary, M., J. Lehner, A. M. Fouda, A. Hamed, J. Ulrich, T. Simmet, T. Syrovets, and A. M. El-Agrody, "Synthesis and evaluation of antitumor activity of 9-methoxy-1H-benzo [f] chromene derivatives", Bioorganic Chemistry, vol. 116: Elsevier, pp. 105402, 2021. Abstract
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El Gaafary, M., A. M. Fouda, H. M. Mohamed, A. Hamed, H. K. A. El-Mawgoud, L. Jin, J. Ulrich, T. Simmet, T. Syrovets, and A. M. El-Agrody, "Synthesis of $\beta$-Enaminonitrile-Linked 8-Methoxy-1H-Benzo [f] Chromene Moieties and Analysis of Their Antitumor Mechanisms", Frontiers in chemistry, vol. 9: Frontiers Media SA, 2021. Abstract
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El Gaafary, M., T. Syrovets, H. M. Mohamed, A. A. Elhenawy, A. M. El-Agrody, A. El-Galil E. Amr, H. A. Ghabbour, and A. A. Almehizia, "Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2, 5-dichlorophenyl)-8-methoxy-1 H-benzo [f] chromene-2-carbonitrile", Crystals, vol. 11, no. 2: MDPI, pp. 184, 2021. Abstract
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2020
Lang, S. J., M. Schmiech, S. Hafner, C. Paetz, K. Werner, and M. El Gaafary, "Chrysosplenol d, a Flavonol from Artemisia annua, Induces ERK1/2-Mediated Apoptosis in Triple Negative Human Breast Cancer Cells", Int. J. Mol. Sci. , vol. 21, pp. 4090, 2020.
Jin, L., M. Schmiech, M. El Gaafary, and X. Zhang, "A comparative study on root and bark extracts of Eleutherococcus senticosus and their effects on human macrophages", Phytomedicine , vol. 68, pp. 153181, 2020.
Nasr, S., M. Rady, A. Sebak, I. Gomaa, W. A. L. I. D. FAYAD, and M. El Gaafary, "A Naturally Derived Carrier for Photodynamic Treatment of Squamous Cell Carcinoma: In Vitro and In Vivo Models", Pharmaceutics , vol. 12, pp. 494, 2020.
Hamed, A., M. Frese, M. El Gaafary, and T. Syrovets, "Synthesis of novel feruloyl dipeptides with proapoptotic potential against different cancer cell lines", Bioorganic Chemistry , vol. 97, pp. 103678, 2020.
Hamed, A., M. Frese, M. El Gaafary, T. Syrovets, N. Sewald, T. Simmet, and M. Shaaban, "Synthesis of novel feruloyl dipeptides with proapoptotic potential against different cancer cell lines", Bioorganic chemistry, vol. 97: Elsevier, pp. 103678, 2020. Abstract
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2019
2016
Ezzat, S. M., M. El Gaafary, A. M. Elsayed, O. M. Sabry, Z. Y. Ali, S. Hafner, M. Schmiech, L. Jin, T. Syrovets, and T. Simmet, "The Cardenolide Glycoside Acovenoside A Affords Protective Activity in Doxorubicin-Induced Cardiotoxicity in Mice.", The Journal of pharmacology and experimental therapeutics, vol. 358, issue 2, pp. 262-70, 2016 Aug. Abstract

The current study aimed to investigate the protective effect of the cardenolide glycoside acovenoside A (AcoA) against doxorubicin-induced cardiotoxicity in mice. AcoA was isolated from the pericarps of Acokanthera oppositifolia to chemical homogeneity and characterized by means of one- and two-dimensional nuclear magnetic resonance spectroscopy. AcoA exhibited relatively low toxicity in mice (LD50 = 223.3 mg/kg bw). Repeated administration of doxorubicin induced cardiotoxicity manifested by reduced activity of myocardial membrane-bound ion pumps and elevated serum biomarkers of myocardial dysfunction, oxidative stress, and inflammation. Pretreatment of doxorubicin-exposed mice with AcoA (11.16 or 22.33 mg/kg bw, i.p.) for 2 weeks after 2 weeks of combined administration of AcoA and doxorubicin protected the animals dose dependently against doxorubicin-induced cardiotoxicity as indicated by normalization of the levels of different myocardial markers of oxidative stress (malondialdehyde, nitric oxide, total antioxidant capacity, and cardiac glutathione), serum myocardial diagnostic marker enzymes (serum cardiac troponin T, creatine kinase isoenzyme MB, aspartate aminotransferase, and lactate dehydrogenase), and inflammatory markers (c-reactive protein, tumor necrosis factor-α, and interleukin-6), as well as myocardial Na(+)/K(+)-ATPase activity. These effects were attributed to the negative impact of AcoA on transcription factors nuclear factor κB and interferon regulatory factor 3/7. Thus acovenoside A might act as a cardioprotective agent to prevent doxorubicin-induced cardiotoxicity.

Syrovets, T., B. Buechele, M. El Gaafary, R. M. Ayala, A. Abderrazak, D. Couchie, D. F. Mahmood, R. Elhage, C. Vindis, M. Laffargue, et al., "Anti-inflammatory and antiatherogenic effects of the NLRP3 inflammasome inhibitor arglabin", NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, vol. 389, no. SUPPL 1: SPRINGER ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES, pp. 34–34, 2016. Abstract
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2015
Abderrazak, A., D. Couchie, D. F. Darweesh Mahmood, R. Elhage, C. Vindis, M. Laffargue, V. Matéo, B. Büchele, M. R. Ayala, M. El Gaafary, et al., "Response to Letter Regarding Article, "Anti-inflammatory and Antiatherogenic Effects of the Inflammasome NLRP3 Inhibitor Arglabin in ApoE2.Ki Mice Fed a High-Fat Diet".", Circulation, vol. 132, issue 21, pp. e250-1, 2015 Nov 24. Abstract
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Abderrazak, A., D. Couchie, D. F. Darweesh Mahmood, R. Elhage, C. Vindis, M. Laffargue, V. Matéo, B. Büchele, M. R. Ayala, M. El Gaafary, et al., "Anti-inflammatory and antiatherogenic effects of the NLRP3 inflammasome inhibitor arglabin in ApoE2.Ki mice fed a high-fat diet.", Circulation, vol. 131, issue 12, pp. 1061-70, 2015 Mar 24. Abstract

BACKGROUND: This study was designed to evaluate the effect of arglabin on the NLRP3 inflammasome inhibition and atherosclerotic lesion in ApoE2Ki mice fed a high-fat Western-type diet.

METHODS AND RESULTS: Arglabin was purified, and its chemical identity was confirmed by mass spectrometry. It inhibited, in a concentration-dependent manner, interleukin (IL)-1β and IL-18, but not IL-6 and IL-12, production in lipopolysaccharide and cholesterol crystal-activated cultured mouse peritoneal macrophages, with a maximum effect at ≈50 nmol/L and EC50 values for both cytokines of ≈ 10 nmol/L. Lipopolysaccharide and cholesterol crystals did not induce IL-1β and IL-18 production in Nlrp3(-/-) macrophages. In addition, arglabin activated autophagy as evidenced by the increase in LC3-II protein. Intraperitoneal injection of arglabin (2.5 ng/g body weight twice daily for 13 weeks) into female ApoE2.Ki mice fed a high-fat diet resulted in a decreased IL-1β plasma level compared with vehicle-treated mice (5.2±1.0 versus 11.7±1.1 pg/mL). Surprisingly, arglabin also reduced plasma levels of total cholesterol and triglycerides to 41% and 42%, respectively. Moreover, arglabin oriented the proinflammatory M1 macrophages into the anti-inflammatory M2 phenotype in spleen and arterial lesions. Finally, arglabin treatment markedly reduced the median lesion areas in the sinus and whole aorta to 54% (P=0.02) and 41% (P=0.02), respectively.

CONCLUSIONS: Arglabin reduces inflammation and plasma lipids, increases autophagy, and orients tissue macrophages into an anti-inflammatory phenotype in ApoE2.Ki mice fed a high-fat diet. Consequently, a marked reduction in atherosclerotic lesions was observed. Thus, arglabin may represent a promising new drug to treat inflammation and atherosclerosis.

El Gaafary, M., B. Büchele, T. Syrovets, S. Agnolet, B. Schneider, C. Q. Schmidt, and T. Simmet, "An α-acetoxy-tirucallic acid isomer inhibits Akt/mTOR signaling and induces oxidative stress in prostate cancer cells.", The Journal of pharmacology and experimental therapeutics, vol. 352, issue 1, pp. 33-42, 2015 Jan. Abstract

Here we provide evidence that αATA(8,24) (3α-acetyloxy-tir-8,24-dien-21-oic acid) inhibits Akt/mammalian target of rapamycin (mTOR) signaling. αATA(8,24) and other tirucallic acids were isolated from the acetylated extract of the oleo gum resin of Boswellia serrata to chemical homogeneity. Compared with related tirucallic acids, αATA(8,24) was the most potent inhibitor of the proliferation of androgen-insensitive prostate cancer cells in vitro and in vivo, in prostate cancer xenografted onto chick chorioallantoic membranes. αATA(8,24) induced loss of cell membrane asymmetry, caspase-3 activation, and DNA fragmentation in vitro and in vivo. These effects were selective for cancer cells, because αATA(8,24) exerted no overt toxic effects on peripheral blood mononuclear cells or the chick embryo. At the molecular level, αATA(8,24) inhibited the Akt1 kinase activity. Prior to all biochemical signs of cellular dysfunction, αATA(8,24) induced inhibition of the Akt downstream target mTOR as indicated by dephosphorylation of S6K1. This event was followed by decreased expression of cell cycle regulators, such as cyclin D1, cyclin E, and cyclin B1, as well as cyclin-dependent kinases CDK4 and CDK2 and phosphoretinoblastoma protein, which led to inhibition of the cell-cycle progression. In agreement with the mTOR inhibition, αATA(8,24) and rapamycin increased the volume of acidic vesicular organelles. In contrast to rapamycin, αATA(8,24) destabilized lysosomal and mitochondrial membranes and induced reactive oxygen species production in cancer cells. The ability of αATA(8,24) to inhibit Akt/mTOR signaling and to induce simultaneously oxidative stress could be exploited for the development of novel antitumor therapeutics with a lower profile of toxic side effects.

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