Publications by authors named "Heba S Rateb"

9 Publications

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Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19.

Int J Pharm 2021 Jan 7;592:120028. Epub 2020 Nov 7.

Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, Minia, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt. Electronic address:

The present work aimed to develop an optimized liposomal formulation for enhancing the anti-viral activity of propolis against COVID-19. Docking studies were performed for certain components of Egyptian Propolis using Avigan, Hydroxychloroquine and Remdesivir as standard antivirals against both COVID-19 3CL-protease and S1 spike protein. Response surface methodology and modified injection method were implemented to maximize the entrapment efficiency and release of the liposomal formulation. The optimized formulation parameters were as follow: LMC of 60 mM, CH% of 20% and DL of 5 mg/ml. At those values the E.E% and released % were 70.112% and 81.801%, respectively with nanosized particles (117 ± 11 nm). Docking studies revealed that Rutin and Caffeic acid phenethyl ester showed the highest affinity to both targets. Results showed a significant inhibitory effect of the optimized liposomal formula of Propolis against COVID-3CL protease (IC50 = 1.183 ± 0.06) compared with the Egyptian propolis extract (IC50 = 2.452 ± 0.11), P < 0.001. Interestingly, the inhibition of viral replication of COVID-19 determined by RT_PCR has been significantly enhanced via encapsulation of propolis extract within the liposomal formulation (P < 0.0001) and was comparable to the viral inhibitory effect of the potent antiviral (remdesivir). These findings identified the potential of propolis liposomes as a promising treatment approach against COVID-19.
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http://dx.doi.org/10.1016/j.ijpharm.2020.120028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647905PMC
January 2021

Design, Synthesis, Antimicrobial and Anti-biofilm Evaluation, and Molecular Docking of Newly Substituted Fluoroquinazolinones.

Med Chem 2019 ;15(6):659-675

Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.

Background: Quinazolines and quinazolinones derivatives are well known for their important range of therapeutic activities.

Objective: The study aims to carry out the synthesis of some derivatives of substituted fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal, and anti-biofilm activities.

Methods: Compounds were chemically synthesized by conventional methods. Structures were established on the basis of spectral and elemental analyses. The antimicrobial potential was tested against various microorganisms using the agar disc-diffusion method. MIC and MBC as well as anti-biofilm activity for the highly active compounds were assessed. Moreover, the computational studies were performed using Auto dock free software package (version 4.0) to explain the predicted mode of binding.

Results: All derivatives (5-8), (10a-g), and (A-H) were biologically tested and showed significant antimicrobial activity comparable to the reference compounds. Compounds 10b, 10c, and 10d had a good MIC and MBC against Gram-positive bacteria, whereas 10b and 10d showed significant MIC and MBC against Gram-negative bacteria. However, compounds E and F exhibited good MIC and MBC against fungi. Compound 10c and 8 exhibited significant anti-biofilm activity towards S. aureus and M. luteus. Molecular docking study revealed a strong binding of these derivatives with their receptor-site and detected their predicted mode of binding.

Conclusion: The synthesized derivatives showed promising antibacterial, antifungal, and antibiofilm activities. Modeling study explained their binding mode and showed strong binding affinity with their receptor-site. The highly active compounds 5 and 10c could be subjected to future optimization and investigation to be effective antimicrobial agents.
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http://dx.doi.org/10.2174/1573406414666181109092944DOI Listing
October 2019

Quinazolinone-Amino Acid Hybrids as Dual Inhibitors of EGFR Kinase and Tubulin Polymerization.

Molecules 2018 Jul 12;23(7). Epub 2018 Jul 12.

Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah 41477, Al-Munawarah, Saudi Arabia.

Some fluoroquinazolinones (⁻) were designed, synthesized and biologically evaluated for their antitumor activity against the two cell lines, MCF-7 and MDA-MBA-231. New derivative (IC = 0.44 ± 0.01 µM) showed antitumor activity, better than that of the reference drug erlotinib (IC = 1.14 ± 0.04 µM) against MCF-7. New derivative (IC = 0.43 ± 0.02 µM) showed higher activity than the reference drug erlotinib (IC = 2.55 ± 0.19 µM) against MDA-MBA-231. Furthermore, the EGFR (epidermal growth factor receptor) and tubulin inhibition assays were carried out for the highest active derivatives to reveal the expected mechanism of action. They exhibited significant results compared to the reference drugs. Molecular docking simulations were performed on EGFR and tubulin binding sites to rationalize the experimental results and describe their binding modes. The results of the molecular modeling study were correlated with that of the antitumor screening.
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http://dx.doi.org/10.3390/molecules23071699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100557PMC
July 2018

Design, Synthesis, Cytotoxic Evaluation and Molecular Docking of New Fluoroquinazolinones as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects.

Int J Mol Sci 2018 06 11;19(6). Epub 2018 Jun 11.

Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia.

A series of new fluoroquinazolinone ⁻ and ⁻ derivatives was designed, prepared and screened for their in vitro cytotoxic activity against human cancer cell lines MCF-7 and MDA-MBA-231. Compounds (IC = 0.35 ± 0.01 µM), (IC = 0.71 ± 0.01 µM), (IC = 0.89 ± 0.02 µM) and (IC = 0.95 ± 0.01 µM) displayed broad spectrum anticancer activity better than the reference drug gefitinib (IC = 0.97 ± 0.02 µM) against MCF-7. Compounds (IC = 0.28 ± 0.02 µM), (IC = 0.38 ± 0.01 µM), (IC = 0.94 ± 0.07 µM) and (IC = 1.09 ± 0.01 µM) showed better activity than the reference gefitinib (IC = 1.30 ± 0.04 µM) against MDA-MBA-231. Moreover, EGFR and tubulin inhibition assays were performed for the highest active derivatives and showed remarkable results comparing to the reference drugs. In order to assess and explain their binding affinities, molecular docking simulation was studied against EGFR and tubulin binding sites. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated.
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http://dx.doi.org/10.3390/ijms19061731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032053PMC
June 2018

Design, synthesis, molecular docking of new lipophilic acetamide derivatives affording potential anticancer and antimicrobial agents.

Bioorg Chem 2018 02 2;76:332-342. Epub 2017 Dec 2.

The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt.

Fifteen new substituted N-2-(2-oxo-3-phenylquinoxalin-1(2H)-yl) acetamides 5a-f, 6a-f, and 8a-c were synthesized by reacting ethyl 2-(2-oxo-3-phenylquinoxalin-1(2H)-yl)acetate with various primary amines including benzylamines, sulfonamides, and amino acids. The in vitro antimicrobial screening of the target compounds was screened to assess their antibacterial and antifungal activity. As a result, seven compounds namely; 5a, 5c, 5d, 6a, 6c, 8b and 8c showed a promising broad spectrum antibacterial activity against both Gram-positive and Gram-negative strains. Among these, the analogs 5c and 6d were nearly as equiactive as ciprofloxacin drug. Meanwhile, four compounds namely; 5c, 6a, 6f and 8c exhibited appreciable antifungal activity with MIC values range 33-40 mg/mL comparable with clotrimazole (MIC 25 mg/mL). In addition, the anticancer effects of the synthesized compounds were evaluated against three cancer lines. The data obtained revealed the benzylamines and sulpha derivatives were the most active compounds especially 5f and 6f ones. Further EGFR enzymatic investigation was carried out for these most active compounds 5f and 6f resulting in inhibitory activity by 1.89 and 2.05 µM respectively. Docking simulation was performed as a trial to study the mechanisms and binding modes of these compounds toward the enzyme target, EGFR protein kinase enzyme. The results revealed good compounds placement in the active sites and stable interactions similar to the co-crystallized reference ligand. Collectively, the analogs 5f and 6f could be further utilized and optimized as good cytotoxic agents.
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http://dx.doi.org/10.1016/j.bioorg.2017.11.019DOI Listing
February 2018

Rational design, synthesis, pharmacophore modeling, and docking studies for identification of novel potent DNA-PK inhibitors.

Bioorg Chem 2017 06 2;72:234-247. Epub 2017 May 2.

Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; Department of Pharmaceutical and Medicinal Chemistry, Pharmacy College, Misr University for Science and Technology, Cairo, Egypt.

Drugs of cancer based upon ionizing radiation or chemotherapeutic treatment may affect breaking of DNA double strand in cell. DNA-PK enzyme has emerged as an attractive target for drug discovery efforts toward DNA repair pathways. Hence, the search for potent and selective DNA-PK inhibitors has particularly considered state-of-the art and several series of inhibitors have been designed. In this article, a novel benchmark DNA-PK database of 43 compounds was built and described. Ligand-based approaches including pharmacophore and QSAR modeling were applied and novel models were introduced and analyzed for predicting activity test for DNA-PK drug candidates. Based upon the modeling results, we gave a report of synthesis of fifteen novel 2-((8-methyl-2-morpholino-4-oxo-4H-benzo[e][1,3]oxazin-7-yl)oxy)acetamide derivatives and in vitro evaluation for DNA-PK inhibitory and antiproliferative activities. These fifteen compounds overall are satisfied with Lipinski's rule of five. The biological testing of target compounds showed five promising active compounds 7c, 7d, 7f, 9e and 9f with micromolar DNA-PK activity range from 0.25 to 5µM. In addition, SAR of the compounds activity was investigated and confirmed that the terminal aryl moiety was found to be quite crucial for DNA-PK activity. Moreover flexible docking simulation was done for the potent compounds into the putative binding site of the 3D homology model of DNA-PK enzyme and the probable interaction model between DNA-PK and the ligands was investigated and interpreted.
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http://dx.doi.org/10.1016/j.bioorg.2017.04.014DOI Listing
June 2017

Discovery of novel phthalimide analogs: Synthesis, antimicrobial and antitubercular screening with molecular docking studies.

EXCLI J 2016 6;15:781-796. Epub 2016 Dec 6.

Chemistry Department, Faculty of Science, Taibah University, 30002, Al-Madinah Al-Munawarah, Saudi Arabia.

In continuation of our endeavor towards the design and development of potent and effective antimicrobial agents, three series of phthalimide derivatives ( and ) were synthesized, fully characterized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the discovery of nine compounds , and (MIC range from 0.49 to 31.5 μg/mL) with potent antibacterial, antifungal, and antimycobacterial activities. Ampicillin, ciprofloxacin, amphotericin B were used as references for antibacterial and antifungal screening respectively, while isoniazid was used as a reference for antimycobacterial testing. Furthermore, molecular modeling studies were done to explore the binding mode of the most active derivatives to M. tuberculosis enoyl reductase (InhA) and DNA gyrase B. Our study showed the importance of both hydrogen bonding and hydrophobic interactions as a key interaction with the target enzymes.
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http://dx.doi.org/10.17179/excli2016-654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318679PMC
December 2016

Synthesis and docking studies of novel benzopyran-2-ones with anticancer activity.

Eur J Med Chem 2010 Sep 1;45(9):3950-9. Epub 2010 Jun 1.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), 11754 Al-Azhar University, Cairo, Egypt.

Novel series of 7-substituted-benzopyran-2-ones was synthesized by incorporating heterocyclic rings as oxadiazole, triazole, pyrazole or pyrazolin-5-one to benzopyran-2-one nucleus at p-7 via methylene-oxy or acetoxy linker. In-vitro anticancer activity was evaluated for these hybrids; twelve compounds were selected by National Cancer Institute for anticancer screening. Among them, compound 9a exhibited broad spectrum antitumor activity showing full panel median growth inhibition (GI(50)) = 5.46 microM. According to docking results using Molsoft ICM 3.4-8c program, the target compounds may act through inhibition of topoismerase 1, where camptothecin is used as ligand.
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http://dx.doi.org/10.1016/j.ejmech.2010.05.050DOI Listing
September 2010

Synthesis and evaluation of some 1,2,3,4-tetrahydropyrimidine-2-thione and condensed pyrimidine derivatives as potential antihypertensive agents.

Arzneimittelforschung 2006 ;56(5):322-7

Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.

Some new tetrahydropyrimidine-2-thione, octahydroquinazoline-2-thione and thiazolo[3,2-a]pyrimidine derivatives have been synthesized and tested for their antihypertensive activity. Among them, compounds 1 and 2b can be considered more potent than the reference, nifedipine (CAS 21829-25-4), while compounds 3b and 10a are equipotent to it. In addition, compound 6 showed significant antihypertensive activity.
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http://dx.doi.org/10.1055/s-0031-1296729DOI Listing
August 2006
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