Publications by authors named "Eman S Habib"

12 Publications

  • Page 1 of 1

VEGFR-Mediated Cytotoxic Activity of Isolated Metabolites: A Biological Evaluation and In Silico Study.

Life (Basel) 2021 Jul 28;11(8). Epub 2021 Jul 28.

Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

Natural products play a remarkable role not only in the synthesis, design, and discovery of new drugs but also as the most prominent source of drugs and bioactive substances. Adding to the search for new sources of safe innovative antitumor drugs, here we reported a phytochemical study on   which revealed promising antiangiogenic agents. Six compounds were isolated and identified as xanthoxyline (), stigmasterol (), oleanolic acid (), salvigenin () rhamnetin () and dihydroquercetin-4'-methyl ether () using nuclear magnetic resonance (NMR) spectroscopic techniques. Compound and are first reported in genus. Both the extract and isolated compounds were evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7). In vivo antiproliferative activity against Ehrlich's ascites carcinoma (EAC) were also assessed. The extract and isolates showed significant reduction in tumor weight, decreased both serum vascular endothelial growth factor B (VEGF-B) levels and vascular endothelial growth factor receptor 2 (VEGFR-2) expression significantly compared to the control EAC group, suggesting an antiangiogenic activity through the inhibition of VEGF signaling. Besides, they displayed reduction in CD34 expression, confirming their antiangiogenic effect. Moreover, the potential affinity of isolated compounds to human estrogen nuclear receptor-alpha (ER-α), the most recognized modulator of VEGFR-2 expression, was virtually estimated through molecular modeling studies. The most promising activity profiles were assigned to the investigated flavonoids, compounds -, as well as the alkyl-phenylketone, compound . Additionally, these four top active compounds showed respective high to intermediate docking scores while possessing preferential binding with ER-α critical pocket residues. Based on the provided data, these isolated compounds illustrated promising inhibitors of VEGF-stimulated angiogenesis, which could be a possible mechanism for their anticancer activity.
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http://dx.doi.org/10.3390/life11080759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398779PMC
July 2021

Chemical profiling, cytotoxic activities through apoptosis induction in MCF-7 cells and molecular docking of bark nonpolar extract.

J Biomol Struct Dyn 2021 Jun 2:1-12. Epub 2021 Jun 2.

Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt.

The chemical constituents of the nonpolar fractions of the bamboo shoot skin were extensively studied. The phytochemical study was divided into two parts: the first deals with isolation of the chemical constituents using different chromatographic techniques that resulted in isolation of four compounds. The chemical structures of the pure isolated compounds were elucidated using different spectroscopic data. The second part deals with identification of the rest of the constituents using the GC technique. Additionally, both crude extract and the pure isolated compounds were investigated for cytotoxic activity. One of the isolated compounds; namely glyceryl 1-monopalmitate showed highly promising effect against the MCF-7 cells with (IC = 19.78 µM) compared to 5-FU (26.98 µM), and it remarkably stimulated apoptotic breast cancer cell death with 31.6-fold (16.13% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Moreover, the identified compounds especially were found to have high binding affinity towards both TPK and VEGFR-2 through the molecular docking studies which highlight its mode of action. HighlightsChemical profiling of bark nonpolar extract was fully identified.Glyceryl 1-monopalmitate showed highly promising effect against the MCF-7 cells with (IC = 19.78 µM) compared to 5-FU (26.98 µM).Glyceryl 1-monopalmitate significantly stimulated apoptotic breast cancer cell death with 31.6-fold by arresting cell cycle at G2/M and preG1 phases.Molecular docking simulation showed good binding affinities towards TPK and VEGFR-2 proteins.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1932599DOI Listing
June 2021

Chemical Constituent Profiling of var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells.

Molecules 2021 Feb 10;26(4). Epub 2021 Feb 10.

Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt.

Different extracts of the Bamboo shoot skin var. pubescens were screened against panel of cancer cell lines and normal one. The cell viability results exhibited that the ethyl acetate extract showed the least vitality percentage of 2.14% of HepG2 cells. Accordingly, it was subjected to chromatographic separation, which resulted in the isolation of a new natural product; 7-hydroxy, 5-methoxy, methyl cinnamate (), together with four known compounds. The structures of the pure isolated compounds were deduced based on different spectroscopic data. The new compound () was screened against the HepG2 and MCF-7 cells and showed IC values of 7.43 and 10.65 µM, respectively. It induced apoptotic cell death in HepG2 with total apoptotic cell death of 58.6% (12.44-fold) compared to 4.71% in control by arresting cell cycle progression at the G1 phase. Finally, compound was validated as EGFR tyrosine kinase inhibitor in both enzymatic levels (IC = 98.65 nM compared to Erlotinib (IC = 78.65 nM). Finally, in silico studies of compound through the molecular docking indicated its high binding affinity towards EGFR protein and the ADME pharmacokinetics indicated it as a drug-like.
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http://dx.doi.org/10.3390/molecules26040940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916669PMC
February 2021

New Antiproliferative Triflavanone from -Isolation, Structure Elucidation and Molecular Docking Studies.

Molecules 2021 Jan 31;26(3). Epub 2021 Jan 31.

Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

In this study isolates from , a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound (), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in : daphnoretin methyl ether (), rutamontine (), neodaphnoretin (), acetyldaphnoretin (), and edgeworthin (); two flavonoids: genkwanin () and -tiliroside (); -hydroxy benzoic acid () and sitosterol glucoside (). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds , and exhibited remarkable cytotoxic activities against HepG2 cells, with IC values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC values of 4.26 and 9.6 μM, respectively. Compound significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. Finally, its apoptosis-inducing activity was further validated through activation of BAX and caspase-9, and inhibition of BCL2 levels. In silico molecular docking experiments revealed a good binding mode profile of the isolates towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK); a common molecular pathway in the development and progression of liver tumors.
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http://dx.doi.org/10.3390/molecules26030739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867015PMC
January 2021

Cytotoxic, Apoptosis-Inducing Activities, and Molecular Docking of a New Sterol from Bamboo Shoot Skin var. pubescens.

Molecules 2020 Nov 30;25(23). Epub 2020 Nov 30.

Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

Phytochemical screening of nonpolar fractions from the methanol extract of the Bamboo shoot skin var. pubescens resulted in the isolation of a new sterol-glucoside-fatty acid derivative (6'--octadeca-8'',11''-dienoyl)-sitosterol-3---d-glucoside (), together with six known compounds. The chemical structures of the pure isolated compounds were deduced based on different spectral data. The isolated compounds were assessed to determine their cytotoxic activity, and the results were confirmed by determining their apoptotic activity. Compound was more cytotoxic against the MCF-7 cells (IC = 25.8 µM) compared to Fluorouracil (5-FU) (26.98 µM), and it significantly stimulated apoptotic breast cancer cell death with 32.6-fold (16.63% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Additionally, RT-PCR results further confirmed the apoptotic activity of compound by the upregulation of proapoptotic genes (P53; Bax; and caspases 3, 8, and 9) and downregulation of the antiapoptotic genes (BCL2). Finally, the identified compounds, especially , were found to have high binding affinity towards both tyrosine-specific protein kinase (TPK) and vascular endothelial growth factor receptor (VEGFR-2) through the molecular docking studies that highlight its mode of action.
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http://dx.doi.org/10.3390/molecules25235650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731115PMC
November 2020

Anti-inflammatory effect of methoxyflavonoids from ( growing in Egypt.

Nat Prod Res 2020 Aug 4:1-5. Epub 2020 Aug 4.

Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.

is a medicinal plant that grows in Sinai Peninsula in Egypt. Phytochemical investigation of methanolic extract led to the isolation of five methoxy flavonoids; Chrysosplenol-D 5,7,4'-trihydroxy- 3,3'-dimethoxy flavone , 5,7-dihydroxy -3,3',4'-trimethoxyflavone , Bonanzin , 3,5,6,7,4'-pentamethoxy flavone a sesquiterpene, Cryptomeridiol and stigmast-5,22-dien-3-O-β-D-glucopyranoside . The anti-inflammatory activity of compounds and was assessed on CaCo2 cells stimulated by lipopolysaccharide (LPS). Both compounds downregulated LPS-induced expression of inflammatory cytokines; tumor necrosis factor alpha (TNFα), interleukin 1β (IL1β), nuclear factor kappa B (NFκB), cyclooxygenase 1 (Cox1), cyclooxygenase 2 (Cox2), and 5-lipoxygenase (5Lox). In vivo, both compounds significantly decreased paw edema thickness in rats relative to carrageenan, showing better anti-inflammatory activity than celecoxib (36.98%) after 1 h (46.60% and 48.11%, respectively). An study was performed, where both compounds were docked into the active site of the crystal structure of the human Cox2 enzyme.
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http://dx.doi.org/10.1080/14786419.2020.1802272DOI Listing
August 2020

Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass .

Mar Drugs 2020 Jul 8;18(7). Epub 2020 Jul 8.

Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

(Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol () was isolated from the methanolic extract of growing in the Red Sea, along with two known first-reported sterols, namely ergosterol () and stigmasterol (), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides.
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http://dx.doi.org/10.3390/md18070354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401251PMC
July 2020

Ergosterol Peroxide from the Egyptian Red Lingzhi or Reishi Mushroom, Ganoderma resinaceum (Agaricomycetes), Showed Preferred Inhibition of MCF-7 over MDA-MB-231 Breast Cancer Cell Lines.

Int J Med Mushrooms 2020 ;22(4):389-396

Chemistry Department, Faculty of Science, Damietta University, New Damietta City, Egypt; Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.

Ergosterol peroxide and ganoderic acid AMI were isolated for the first time from the mycelium of the Egyptian Ganoderma resinaceum mushroom. The structure of these two metabolites was established by detailed analysis of 1D and 2D NMR. The isolated compounds were tested for their antitumor in vitro activities in MCF-7 and MDA-MB-231 breast cancer cell lines. Ergosterol peroxide showed preferred inhibition of MCF-7 (ER +ve) cell lines relative to MDA-MB-231 (ER -ve) cell lines with an IC50 of 1.18 μM and 12.82 μM respectively. Our data suggest that ergosterol peroxide targets estrogen receptors.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2020034223DOI Listing
February 2021

New Cytotoxic Natural Products from the Red Sea Sponge .

Mar Drugs 2020 May 3;18(5). Epub 2020 May 3.

Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia 61111, Egypt.

Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (), and a cerebroside, stylissoside A (), from the methanol extract of the Red Sea sponge . Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, and , displayed strong cytotoxicity against the MCF-7 cell line, with IC values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC at 36.8 ± 0.16 µM for and IC 30.5 ± 0.23 µM for compared to the standard drug cisplatin. Molecular docking experiments showed that and displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.
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http://dx.doi.org/10.3390/md18050241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281077PMC
May 2020

Isolates From Inhibit Progression Of Hepatocellular Carcinoma And .

Nat Prod Res 2021 Jun 17;35(11):1799-1807. Epub 2019 Jul 17.

Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.

Herein, we investigated effect of Thymelaea hirsuta isolates on hepatocellular carcinoma. Methanolic extract of led to isolation of two new compounds [6` hydroxyDaphnoretin (9) and Mithnin (15)], seven compounds reported for the first time from genus Thymelaea [Dotriacontanol (1), and 3-ketopentatriacontanoic (2), Docosylcoumarate (5), Docosylcaffeate (6), Daphnodorin B (11), 3`` -epi-dihydrodaphnodorin B (12) and Wikstaiwanone B (14)], and six known compounds. Eight compounds (5, 6, 9, 10, 11, 12, 14, and 15) showed significant anti-proliferative activity on HepG2 cells. These compounds caused significant reduction (p < 0.05) in serum levels of AST, ALT, ALP, total bilirubin, GGT, and AFP, a significant increase in and expression, and a significant decrease in gene in liver as compared to the HCC group. These results indicate that isolates inhibited HCC progression, possibly through induction of apoptosis and therefore they could be used as a beneficial source for treating HCC.
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http://dx.doi.org/10.1080/14786419.2019.1643859DOI Listing
June 2021

Selective kappa opioid antagonists for treatment of addiction, are we there yet?

Eur J Med Chem 2017 Dec 10;141:632-647. Epub 2017 Oct 10.

National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.

Kappa opioid receptor (KOP) is a G-protein coupled receptor mainly expressed in the cerebral cortex and hypothalamus. It is implicated in nociception, diuresis, emotion, cognition, and immune system functions. KOP agonists possess a strong analgesic effect accompanied by a feeling of dysphoria. On the other hand, antagonists of this receptor were found to block depression, anxiety, and drug-seeking behaviors in animal models. Recently, great interest has been given to the development of selective KOP antagonists as an addiction treatment that does not cause dependence itself or show high relapse rates like the currently used agents. This review provides a comprehensive survey of the KOP antagonists developed for this purpose together with their in vivo studies and clinical trials. In addition, a future perspective and recommendations for the work needed to develop clinically relevant KOP antagonists are presented.
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http://dx.doi.org/10.1016/j.ejmech.2017.10.012DOI Listing
December 2017

IN VITRO ANTI-PROTOZOAL ACTIVITY OF PROPOLIS EXTRACT AND CYSTEINE PROTEASES INHIBITOR (PHENYL VINYL SULFONE) ON BLASTOCYSTIS SPECIES.

J Egypt Soc Parasitol 2016 Aug;46(2):261-272

Blastocystis is one of the commonest enteric protozoan parasites worldwide. Despite its controversial clinical significance, frequent association with symptoms has necessitated treatment of cases with persistent symptoms. For long time, metronidzole (MTZ) was considered as a basic drug for blastocystosis treatment, however reports of treatment failure as well as its well-known side effects has promoted the search for more safe and effective alternatives. In vitro antiprotozoal activity of ethanolic extract of Egyptian propolis and a cysteine protease inhibitor, phenyl vinyl sulfone (PVS) on Blastocystis spp. was assessed through challenging with graded concentrations of propolis extract (125, 250, 500 & 1000pg/ml) and PVS (100, 200 and 300 ptg/ml) compared to MTZ (10, 50 and 100 pg/ml) and viable parasites were counted after 24, 48 and 72 hr. of incubation. Molecular subtyling of Blastocystis spp. was done using subtype specific sequence-tagged site (STS) primers. Propolis extract inhibited the growth of Blastocystis spp. in both of the detected subtypes (STI and ST3), which was especially observed in cultures exposed to 500 & 1000 μg/ml through all incuba- tion periods with the later concentration producing comparable results to MTZ. While PVS showed significant parasite count reduction on ST3 isolates, especially with the highest concentration, however the effect on STl isolate was nonsignificant. These findings highlight the potential antiprotozoal activity of propolis extract as a potent natural alternative for MTZ in treatment of blastocystosis.
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August 2016
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