Publications by authors named "Mostafa M Hegazy"

4 Publications

  • Page 1 of 1

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

Drug Des Devel Ther 2021 31;15:2325-2337. Epub 2021 May 31.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia.

Introduction: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance.

Methods: Three semi-synthetic series of compounds (, , and ) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of L. (-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities.

Results: Compounds and showed superior inhibitory activity against EGFR (IC: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds and exhibited the highest cytotoxic activity with average IC values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites.

Discussion: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.
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http://dx.doi.org/10.2147/DDDT.S310820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178614PMC
May 2021

Phytochemical Profiling, In Vitro and In Silico Anti-Microbial and Anti-Cancer Activity Evaluations and Staph GyraseB and -TOP-IIβ Receptor-Docking Studies of Major Constituents of L. Aqueous-Ethanolic Extract and Its Subsequent Fractions: An Approach to Validate Traditional Phytomedicinal Knowledge.

Molecules 2021 Jan 22;26(3). Epub 2021 Jan 22.

Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt.

, an edible halophytic plant, is part of the traditional medicine chest in the Mediterranean region for symptomatic relief of diabetes, hypertension, wound healing, burns, infections, and rheumatoid arthritis pain. The current study aimed to characterize phytoconstituents, and the evaluations of the anti-microbial-biofilm, and anti-cancers bioactivities of the plant's mother liquor, i.e., aqueous-ethanolic extract, and its subsequent fractions. The in silico receptors interaction feasibility of major constituents with Staph GyraseB, and human topoisomerase-IIβ (-TOP-IIβ) were conducted to confirm the plant's anti-microbial and anti-cancer biological activities. Thirty-eight secondary metabolites of flavonoids, stilbene, phenolic acids, alkaloids, and coumarin classes identified by LC-ESI-TOF-MS spectrometric analysis, and tiliroside (kaempferol-3-O-(6''''--coumaroyl)-glucoside, 19.8%), zygophyloside-F (12.78%), zygophyloside-G (9.67%), and isorhamnetin-3-O-glucoside (4.75%) were identified as the major constituents. A superior biofilm obliteration activity established the minimum biofilm eradication concentration (MBEC) for the chloroform fraction at 3.9-15.63 µg/mL, as compared to the positive controls (15.63-31.25 µg/mL) against all the microbial strains that produced the biofilm under study, except the . The aqueous-ethanolic extract showed cytotoxic effects with IC values at 3.47, 3.19, and 2.27 µg/mL against MCF-7, HCT-116, and HepG2 cell-lines, respectively, together with the inhibition of TOP-IIβ with IC value at 45.05 ng/mL in comparison to its standard referral inhibitor (staurosporine, IC, 135.33 ng/mL). This conclusively established the anti-cancer activity of the aqueous-ethanolic extract that also validated by in silico receptor-binding predicted energy levels and receptor-site docking feasibility of the major constituents of the plant's extract. The study helped to authenticate some of the traditional phytomedicinal properties of the anti-infectious nature of the plant.
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http://dx.doi.org/10.3390/molecules26030577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866194PMC
January 2021

Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach.

Nat Prod Bioprospect 2020 Dec 22;10(6):453-462. Epub 2020 Oct 22.

Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University (Boys), Cairo, 11884, Egypt.

Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. We used 3 different conformations of protease target (6M0K, 6Y2F and 7BQY) and two different score functions to strengthen the probability of inhibitors discovery. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or both COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of both targets. The top 7 hits are, flacourticin (3), sagerinic acid (16), hordatine A (23), hordatine B (24), N-feruloyl tyramine dimer (25), bisavenanthramides B-5 (29) and vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds.
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http://dx.doi.org/10.1007/s13659-020-00275-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579552PMC
December 2020

Anti-Oral Pathogens of (L.) and (L.) Flower Volatile Oils in Comparison with Chlorhexidine in Accordance with Their Folk Medicinal Uses.

Medicina (Kaunas) 2019 Jun 24;55(6). Epub 2019 Jun 24.

Pharmacognosy Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt.

: Teeth decay and plaque are complicated problems created by oral pathogens. (L.) and (L.) are two ornamental evergreen plants widely distributed in Egypt. These plants are traditionally used for oral hygienic purposes. This study aims to elucidate the volatile oil constituents obtained from the flowers of these plants and evaluate the antimicrobial activity of these volatile oils against specific oral pathogens in comparison to chlorhexidine. The flowers obtained from both plants were extracted by n-hexane. GC-MS spectrometry was used to identify the constituents. Minimum inhibitory concentrations (MICs) were measured using tetrazolium salt (2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) (XTT). GC-MS analysis revealed the presence of 32 and 29 compounds, representing 100% of the volatile constituents of and , respectively. The GC-MS analysis showed more than 60% of the volatile oil constituents are represented in both plants with different proportions. Chlorhexidine exerted stronger activity than tested plants against all microorganisms. flower extract was more active against all tested microorganisms than . Of note was the effect on , which was inhibited by 100% at 12.5 and 25 µg/mL of and , respectively. The growth of was also completely inhibited by 25 µg/mL of the extract. MIC90 and MIC were also calculated, which revealed the superiority of over against all tested oral pathogens. flower volatile oils showed a potential anti-oral pathogen activity at relatively low concentrations. Also, and demonstrated a strong activity against tooth decay's notorious bacteria . Both plants can be potential substituents to chlorhexidine. Formulating the constituents of these plants in toothpastes and mouthwashes as anti-oral pathogen preparations can be an interesting future plan.
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http://dx.doi.org/10.3390/medicina55060301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631167PMC
June 2019
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