Publications by authors named "Salwa M El-Hallouty"

10 Publications

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Insights of doxorubicin loaded graphene quantum dots: Synthesis, DFT drug interactions, and cytotoxicity.

Mater Sci Eng C Mater Biol Appl 2021 Mar 29;122:111921. Epub 2021 Jan 29.

Environmental and Smart Technology Group (ESTG), Faculty of Science, Fayoum University, 63514 Fayoum, Egypt; Materials Science & Engineering Department, School of Innovative Design Engineering, Egypt-Japan University of Science and Technology (E-JUST), 179 New Borg El-Arab City, Egypt. Electronic address:

Carbon nanomaterials (CNMs) such as graphene quantum dots (GQDs), graphene oxide nanosheets (GO), single and multiwalled carbon nanotubes (SWCNTs, MWCNTs) exhibit different drug loading capacities, release rates, and targeting abilities. This explains the reported discrepancy of their associated therapeutic efficiencies when used as drug carrier systems. In this study, for the first time, two different types of GQDs named GQDs1 and GQDs2 were synthesized, fully characterized, loaded with the chemotherapeutic Doxorubicin (DOX) and compared with other CNMs under the same conditions. The effects of shape (spheres, tubes and sheets), size (30-180 nm), and surface charge (-64.9 to -11.85 mv) of the synthesized CNMs on DOX loading and release efficiency as well as cytotoxicity against MCF-7 cells were investigated. Furthermore, the biosafety of the synthesized GQDs was studied both at the in vitro level using human WI-38 cells and at the in vivo level at low and high doses of 5 and 20 mg/Kg using healthy female Wister rats. Results revealed that GO nanosheets showed the highest DOX loading capacity reaching 2.85 mg/mg while GQDs1 exhibited the highest release rate of 78.1%. The in vitro cytotoxicity evaluation indicated that the smallest spherical nanomaterial among the tested CNMs, namely GQDs1 was the most efficient one on delivering DOX into the cells and inhibiting their proliferation. Regarding the biosafety, all CNMs displayed no noticeable cytotoxicity against WI-38, except for GQDs2. Moreover, hematological, biochemical and histological assessment of both kidneys and livers of treated rats assured the high biosafety level. We also present new insights on the first principle calculations investigating the adsorption of DOX on GO and GQDs. The calculations showed that DOX molecules adsorbed almost equally on both nanoforms, however, the flaky nature of our GO monolayers allowed for sandwich-like structures to exist making its loading capacity superior over GQDs. Based on this comprehensive study, GQDs is the most promising type of the tested CNMs to be used in further studies.
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http://dx.doi.org/10.1016/j.msec.2021.111921DOI Listing
March 2021

Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors.

Bioorg Med Chem 2020 09 21;28(18):115657. Epub 2020 Jul 21.

Drug Bioassay-Cell Culture Laboratory, Department of Pharmacognosy, National Research Centre, Dokki, Giza 12622, Egypt.

Heterocyclic rings such as thiazole and benzimidazole are considered as privileged structures, since they constitute several FDA-approved drugs for cancer treatment. In this work, a new set of 2-(2-(substituted) hydrazinyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl) thiazoles 4a-q were designed as epidermal growth factor receptor (EGFR) inhibitors and synthesized using concise synthetic methods. The new target compounds have been evaluated in vitro for their suppression activity against EGFR TK. Compounds 4n, 4h, 4i, 4a and 4d exhibited significant potency in comparison with erlotinib which served as a reference drug (IC50, 71.67-152.59 nM; IC50 erlotinib, 152.59 nM). Furthermore, MTT assay revealed that compounds 4j, 4a, 4f, 4h, 4n produced the most promising cytotoxic potency against the human breast cancer cell line (MCF-7) (IC50; 5.96-11.91 µM; IC50 erlotinib; 4.15 µM). Compound 4a showed promising activity as EGFR TK inhibitor as well as anti-breast cancer agent. In addition, 4a induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells. Moreover, 4a upregulated the oncogenic parameters; caspase-3, p53, Bax/Bcl-2 as well as it inhibited the level of PARP-1 enzyme. QSAR study was carried out for the new derivatives and it revealed the goodness of the models. Furthermore, molecular docking studies represented the binding modes of the promising compounds in the active pocket of EGFR.
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http://dx.doi.org/10.1016/j.bmc.2020.115657DOI Listing
September 2020

Crude Methanol Extract of Rosin Gum Exhibits Specific Cytotoxicity against Human Breast Cancer Cells via Apoptosis Induction.

Anticancer Agents Med Chem 2020 ;20(8):1028-1036

Biochemistry Department, Cairo University Research Park (CURP), Cairo University, Giza 12613, Egypt.

Background: Rosin (Colophony) is a natural resin derived from species of the pine family Pinaceae. It has wide industrial applications including printing inks, photocopying paper, adhesives and varnishes, soap and soda. Rosin and its derivatives are employed as ingredients in various pharmaceutical products such as ointments and plasters. Rosin-based products contain allergens that may exert some occupational health problems such as asthma and contact dermatitis.

Objective: Our knowledge of the pharmaceutical and medicinal properties of rosin is limited. The current study aims at investigating the cytotoxic potential of Rosin-Derived Crude Methanolic Extract (RD-CME) and elucidation of its mode-of-action against breast cancer cells (MCF-7 and MDA-MB231).

Methods: Crude methanol extract was prepared from rosin. Its phenolic contents were analyzed by Reversed- Phase High-Performance Liquid Chromatography (RP-HPLC). Antioxidant activity was evaluated by DPPH radical-scavenging assay. Antiproliferation activity against MCF-7 and MDA-MB231 cancerous cells was investigated by MTT assay; its potency compared with doxorubicin as positive control and specificity were assessed compared to two non-cancerous cell lines (BJ-1 and MCF-12F). Selected apoptosis protein markers were assayed by western blotting. Cell cycle analysis was performed by Annexin V-FITC/PI FACS assay.

Results: RD-CME exhibited significant and selective cytotoxicity against the two tested breast cancer cells (MCF-7 and MDA-MB231) compared to normal cells as revealed by MTT assay. ELISA and western blotting indicated that the observed antiproliferative activity of RD-CME is mediated via the engagement of an intrinsic apoptosis signaling pathway, as judged by enhanced expression of key pro-apoptotic protein markers (p53, Bax and Casp 3) relative to vehicle solvent-treated MCF-7 control cells.

Conclusion: To our knowledge, this is the first report to investigate the medicinal anticancer and antioxidant potential of crude methanolic extract derived from colophony rosin. We provided evidence that RD-CME exhibits strong antioxidant and anticancer effects. The observed cytotoxic activity against MCF-7 is proposed to take place via G2/M cell cycle arrest and apoptosis. Colophony resin has a great potential to join the arsenal of plantderived natural anticancer drugs. Further thorough investigation of the potential cytotoxicity of RD-CME against various cancerous cell lines is required to assess the spectrum and potency of its novel activity.
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http://dx.doi.org/10.2174/1871520620666200423074826DOI Listing
May 2021

Evaluation of cytotoxicity, biochemical profile and yield components of groundnut plants treated with nano-selenium.

Biotechnol Rep (Amst) 2019 Dec 12;24:e00377. Epub 2019 Sep 12.

Pharmacognosy Department, National Research Centre, Dokki, Cairo, Egypt.

Knowledge about the risks of the nanoparticles application on the plant development and human health is still limited. Different concentrations of nano-selenium (0, 20 and 40 ppm) were applied to three different Egyptian groundnut ( l.) cultivars; (NC, Gregory and Giza 6) under sandy soil conditions at vegetative growth stage to investigate their effects on yield components, protein profile, fatty acids composition, total antioxidant content and cytotoxicity of yielded seeds. The results indicate that the tested Nano-Selenium (Nano-Se) concentrations improved yield components and seeds oil. However, Nano-Se altered protein signatures as well as fatty acids composition by increasing unsaturated fatty acids and/or decreasing saturated fatty acids as compared with control, the cytotoxicity assessments proved safety of the yield for human health.
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http://dx.doi.org/10.1016/j.btre.2019.e00377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796563PMC
December 2019

Synthesis, Cytotoxicity and Molecular Docking Simulation of Novel bis-1,4-Dihydropyridines Linked to Aliphatic or Arene Core via Amide or Ester-Amide Linkages.

Mini Rev Med Chem 2020 ;20(9):801-816

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Objective: Novel bis(1,4-dihydropyridine-3,5-dicarbonitrile) derivatives linked to aliphatic or aromatic cores via amide or ester-amide linkages were prepared and their structures were confirmed by several spectral tools.

Methods: The synthesis of novel N,N'-(alkanediyl)bis(2-(2-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin- 4-yl)phenoxy)acetamide) by acid-catalyzed condensation of the bis-aldehydes with four equivalents of 3-aminocrotononitrile was reported.

Results: The structures of the synthesized compounds were confirmed by different spectral tools. The molecular docking stimulation studies indicated that the prepared compounds bind to the active site of cellular inhibitor apoptotic protein (cIAP1-BIR3). MTT assay for the novel bis(1,4-dihydropyridines) was performed on two different human cell lines (A549 and HCT116).

Conclusion: Compound 5a showed higher cytotoxic activity against A549. Compound 5d showed moderate activity against HCT116. The rest of compounds indicated lower or no activity against both cell lines.
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http://dx.doi.org/10.2174/1389557519666190919160019DOI Listing
January 2021

Biological Activity, Apoptotic Induction and Cell Cycle Arrest of New Hydrazonoyl Halides Derivatives.

Anticancer Agents Med Chem 2019 ;19(9):1141-1149

Chemistry Department (Biotechnology- Biomolecular Chemistry Program), Faculty of Science, Cairo University, Giza, Egypt.

Background: The hydrazonoyl halides are presently an important target in the field of medicinal chemistry. The interest in the chemistry of hydrazonoyl halides is a consequence of the fact that they undergo a wide variety of reactions which provide routes to a myriad of both heterocyclic and acyclic compounds. In addition, they have diverse biological activities such as antiviral, anthelmintic, antiarthropodal, fungicidal, herbicidal, insecticidal, pesticidal, acaricidal and miticidal Activity correlated to the presence of hydrazonoyl halides. Moreover, many applications in both industrial and pharmaceutical fields have been found to be associated with these halides. Depending on the above facts and continuation to our work, we herein report on the evaluation of the anticancer activity of these two halides prepared according to the published work and trying to know their molecular mechanism that they proceed to stop proliferation and metastasis of tumor cells by molecular tools such as real time PCR using different apoptotic genes, and cell cycle assay.

Objective: The goal of this present study is to bring attention to the biological activities of hydrazonoyl halides and the molecular pathway they follow to exert their role in apoptotic death of cancer cell.

Methods: Synthesis of hydrazonoyl halides 2c and 2f. The cytotoxic effect against different human cancer cell lines PC3, HepG-2, HCT-116, MCF-7 and also on normal human cell lines as MCF-10 and MCF-12 in a monolayer culture model was evaluated. Their mechanism of action inside cancer cell was evaluated using different molecular tools.

Conclusion: Strong and promising chemotherapeutic hydrazonoyl halides (2a-2f) were evaluated for their different biological activities. As antimicrobial agents, results indicated that three compounds 2a, 2e and 2f exhibited high activity against two tested gram positive bacteria Staphylococcus aureus, Bacillus subtilis, and gram negative ones Escherichia coli, and Pseudomonas aeruginosa, the rest of the compounds were found to be moderately active against the tested microorganisms. Regarding their antifungal effect, compound 2c exhibited potent and promising effect against Candida albicans, while 2b was the most potent toward Aspergillus flavus Link. The compound 2f has repellent effect. With respect to the in vitro antitumor screening, this was done on different human cancer cell lines; namely PC3, HepG-2, HCT-116, MCF-7 and also on normal human cell lines; as MCF-10 and MCF-12 (normal breast epithelial cell and non-tumorigenic breast epithelial cell line) in a monolayer culture model where screening has been conducted at 100μg/ml (single dose test). Single dose test (100μg/ml) showed that, in case of PC3, all compounds have cytotoxic activity over 90% inhibition, 4 compounds have cytotoxic activity with 100% inhibition with Human colon cancer cell line, 4 compounds showed over 90% inhibition with MCF7 cell line and 4 compounds showed cytotoxic activity over 90% inhibition with HepG-2. Results of IC50 values for most promising compounds showed compounds with values lower than 20μM for all tested human cancer cell line. The promising hydrazonoyl halide 2c and 2f were selected for molecular study to know how they could act inside cancer cell causing death. Two biochemical tests were performed using the two halides 2c and 2f to predict their mechanism of action against breast carcinoma. Real time PCR analysis indicates that the two compounds induced the apoptosis of MCF7 cells through the up regulation of caspase-3, BAX mediated P53 mechanism but unfortunately, they promote the expression of anti-apoptotic protein BCL2. Also, cell cycle assay was performed using two different cell lines MCF7 and HCT116 and data revealed that the two compounds 2c and 2f induced apoptotic cells death of both lines via cell growth arrest at G2/M phase. In addition, it was noted that 2c induced arrest in the two lines more efficiently than 2f at G2/M phase.
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http://dx.doi.org/10.2174/1871520619666190306123658DOI Listing
April 2020

Kinase Inhibitory Activities and Molecular Docking of a Novel Series of Anticancer Pyrazole Derivatives.

Molecules 2018 Nov 24;23(12). Epub 2018 Nov 24.

Pharmacognosy Department, Drug Bioassay-Cell Culture Laboratory, National Research Center, Dokki, Giza 12622, Egypt.

A series of novel 1,3,4-triarylpyrazoles containing different heterocycles has been prepared, characterized and screened for their in vitro antiproliferative activity against HePG-2, MCF-7, PC-3, A-549 and HCT-116 cancer cell lines. The biological results revealed that compound showed the highest anticancer activity so it was subjected to a kinase assay study where it reduced the activity of several protein kinases including AKT1, AKT2, BRAF V600E, EGFR, p38α and PDGFRβ at 100 μM using the radiometric or ADP-Glo assay method. Molecular docking simulation supported the initial kinase assay and suggested a common mode of interaction at the ATP-binding sites of these kinases, which demonstrates that compound is a potential agent for cancer therapy deserving further research.
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http://dx.doi.org/10.3390/molecules23123074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321587PMC
November 2018

Synthesis, Anticancer Screening and Molecular Docking Studies of New Heterocycles with Trimethoxyphenyl Scaffold as Combretastatin Analogues.

Mini Rev Med Chem 2018 ;18(8):717-727

Applied Organic Chemistry Department, National Research Centre, 12622, Dokki, Giza, Egypt.

Background: In this study, synthesis, molecular docking and anticancer screening of new series of substituted heterocycles with trimethoxy phenyl scaffold as Combretastatin analogues were described. Substituted pyridines were synthesized via the reaction of (E)-3-(dimethylamino)-1-(3,4,5- trimethoxyphenyl)prop-2-en-1-one (2) with active methylene reagents. Substituted pyrimidines were prepared by the reaction of the enaminone (2) with heterocyclic amines and 6-amino thiouracil. Furthermore, a series of pyrazoles substituted with trimethoxyphenyl scaffold were prepared by the reaction of the enaminone 2, with selected examples of hydrazonoyl halides.

Conclusion: The cytotoxic effect of the newly compounds was evaluated against HePG-2, HCT-116, MCF-7 and PC3 cancer cell lines. Among the new products, compounds 2, 3, 7 and 10 were found to exhibit promising results as anticancer agents. The IC50 values of 2, 3 and 7 were 54.6, 77.4 and 47.4 on PC3 respectively. Also, compound 2 had IC50 28.06 on MCF7. Moreover, the selectivity index indicated that compounds 2 and 3 are safe.
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http://dx.doi.org/10.2174/1389557517666170425104241DOI Listing
May 2018

Nonclassical antifolates, part 4. 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols as a new class of DHFR inhibitors: synthesis, biological evaluation and molecular modeling study.

Eur J Med Chem 2013 Aug 4;66:135-45. Epub 2013 Jun 4.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.

A new series of compounds possessing 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol skeleton was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, antitumor and schistosomicidal activities. Four active compounds were allocated, the antibacterial 22 (comparable to gentamicin and ciprofloxacin), the schistosomicidal 29 (comparable to praziquantel), the DHFR inhibitor 34 (IC₅₀ 0.03 μM, 2.7 fold more active than MTX), and the antitumor 36 (comparable to doxorubicin). Molecular modeling studies concluded that recognition with key amino acid Leu4 and Val1 is essential for DHFR binding. Flexible alignment and surface mapping revealed that the obtained model could be useful for the development of new class of DHFR inhibitors.
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http://dx.doi.org/10.1016/j.ejmech.2013.05.039DOI Listing
August 2013

Screening of natural products for therapeutic activity against solid tumors.

Indian J Exp Biol 2010 Mar;48(3):258-64

Department of Pharmacognosy, Pharmaceutical Sciences Division, National Research Centre, Dokki, Giza 12622, Egypt.

Most of the currently used cancer therapeutics are natural products. These agents were generally discovered based on their toxicity to tumour cells using various bioassays. Although the exact mechanisms of action of the most commonly used cancer therapeutics such as anthracyclins, podophyllotoxins and camptothecin are incompletely understood, it is becoming increasingly clear that these agents often show complex modes of action at the cellular level, interacting with numerous targets. Such complex modes of action may be the very reason for clinical efficacy. For discovering new cytotoxic anticancer drugs sophisticated screening methods were used. The principles of such screening projects conducted, using collections of purified natural products or extracts from plants have been described. By performing simple but robust prescreening tests such as the brine shrimp assay, bioactive extracts can be identified. Extracts (65) prepared from a collection of Egyptian plants were identified that showed cytotoxity on HepG2 cells. Interestingly, 22 (33%) of these raw extracts, induced > 2-fold induction of caspase-cleavage activity in a colon carcinoma cell line, consistent with induction of apoptosis. Only a fraction of the diversity of the biosphere has been tested for biological activity and novel cancer therapeutics remains to be discovered.
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March 2010
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