Mohammad Ghattas

Mohammad Ghattas
Al Ain University · College of Pharmacy

PhD

About

46
Publications
8,096
Reads
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338
Citations
Citations since 2017
33 Research Items
300 Citations
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2017201820192020202120222023020406080
2017201820192020202120222023020406080
Introduction
Design and discovery of new inhibitors for different drug targets using structure-based drug design. Investigating the aggregation molecular behavior of small organic molecules using molecular dynamics simulations.
Additional affiliations
September 2018 - October 2018
Al Ain University
Position
  • Head of Faculty
April 2016 - present
Al Ain University
Position
  • Professor (Associate)
August 2013 - March 2016
Al Ain University
Position
  • Professor (Assistant)

Publications

Publications (46)
Article
Small molecule compounds which form colloidal aggregates in solution are problematic in early drug discovery: adsorption of the target protein by these aggregates can lead to false positives in inhibition assays. In this work, we probe the molecular basis of this inhibitory mechanism using molecular dynamics simulations. Specifically, we examine in...
Article
Full-text available
The need for new antibacterial agents is increasingly becoming of great importance as bacterial resistance to current drugs is quickly spreading. Enoyl acyl carrier protein reductases (FabI) are important enzymes for fatty acid biosynthesis in bacteria and other microorganisms. In this project, we conducted structure‐based virtual screening against...
Article
Full-text available
GW-2974 is a potent tyrosine kinase receptor inhibitor while SCH-442416 is a potent adenosine receptors’ antagonist with high selectivity towards human adenosine A 2A receptor over other adenosine receptors. The two compounds were reported to possess anti-cancer properties. This study aimed to investigate whether stabilization of human telomeric G-...
Chapter
Virtual screening (VS) is increasingly becoming key in our search for novel drugs against emerging therapeutic targets. Accordingly, this book chapter provides a brief description on the best practices adopted in the pre-VS process. It starts with an illustration of available ligand libraries, their types, and various parameters to be considered wh...
Article
Full-text available
The main protease enzyme (Mpro) of SARS-CoV-2 is one of the most promising targets for COVID-19 treatment. Accordingly, in this work, a structure-based virtual screening of 3.8 million ligand libraries was carried out. After rigorous filtering, docking, and post screening assessments, 78 compounds were selected for biological evaluation, 3 of which...
Article
Full-text available
Lara Alzyoud,1 Mohammad A Ghattas,1,2 Noor Atatreh1,2 1College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates; 2AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab EmiratesCorrespondence: Mohammad A Ghattas; Noor Atatreh, Email mohammad.ghattas@aau.ac.ae; noor.atatreh@aau.ac.aeAbstract: The current...
Article
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The featureless interface formed by protein–protein interactions (PPIs) is notorious for being considered a difficult and poorly druggable target. However, recent advances have shown PPIs to be druggable, with the discovery of potent inhibitors and stabilizers, some of which are currently being clinically tested and approved for medical use. In thi...
Article
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Despite available treatments, breast cancer is the leading cause of cancer-related death. Knowing that the tyrosine phosphatase SHP2 is a regulator in tumorigenesis, developing inhibitors of SHP2 in breast cells is crucial. Our study investigated the effects of new compounds, purchased from NSC, on the phosphatase activity of SHP2 and the modulatio...
Preprint
Full-text available
GW-2974 is a potent inhibitor for the tyrosine kinase receptor. It inhibits EGFR and ErbB-2 in tumor cells with high selectivity towards malignant over normal cells. SCH-442416 is a potent antagonist for adenosine receptor with high selectivity towards human A2a receptor over other adenosine receptors. The two compounds were reported to possess ant...
Article
The anti-diabetic activities of a series of chloropyrimidine derviatives 2a-k and 4a-k were investigated after they were designed, synthesized, and docked against the GLP-1 receptor target. In comparison to exenatide, which was utilized as a reference drug, the three chloropyrimidine synthesized compounds 2c, 2f and 4c exhibited potent in vitro and...
Article
Full-text available
COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). The aim of this study is to target the SARS-CoV-2 virus main protease (Mpro) via structure-based virtual screening. Consequently, > 580,000 ligands were processed via several fi...
Article
Full-text available
This work demonstrates synthetic strategies for the incorporation of a synthesized pyrimidine glucagon-like peptide-1 (GLP-1) agonist into alginate-coated ZIF-8. The prepared pyrimidine GLP-1 agonist used for the treatment of diabetes type II, was trapped inside polymer coated ZIF-8. The encapsulation of the GLP-1 agonist was confirmed by UV-visibl...
Article
Full-text available
GM1-gangliosidosis, a lysosomal storage disorder, is associated with ~ 161 missense variants in the GLB1 gene. Affected patients present with β-galactosidase (β-Gal) deficiency in lysosomes. Loss of function in ER-retained misfolded enzymes with missense variants is often due to subcellular mislocalization. Deoxygalactonojirimycin (DGJ) and its der...
Article
Background View to its interesting role in the peptidoglycan biosynthesis pathway the enzyme UDP-N- acetylglucosamine enolpyruvyl transferase is an attractive target to develop new antibacterial agents, it catalyzes the first key step of this pathway and its inhibition leads to the bacterial cell death. Fosfomycin is known as the natural inhibitor...
Article
Full-text available
Schindler disease is a rare autosomal recessive lysosomal storage disorder caused by a deficiency in alpha-N-acetylgalactosaminidase (α-NAGA) activity due to defects in the NAGA gene. Accumulation of the enzyme’s substrates results in clinically heterogeneous symptoms ranging from asymptomatic individuals to individuals with severe neurological man...
Article
Full-text available
Butyrylcholinesterase (BChE) plays an important role in the progression of the Alzheimer’s disease. In this study, we used a structure-based virtual screening (VS) approach to discover new BChE inhibitors. A ligand database was filtered and docked to the BChE protein using Glide program. The outcome from VS was filtered and the top ranked hits were...
Article
Full-text available
Interaction mechanisms of human serum albumin (HSA) with safranal and crocin were studied using UV-Vis absorption, fluorescence quenching and circular dichroism (CD) spectroscopies as well as molecular docking techniques. Changes in absorbance and fluorescence of HSA upon interactions with both compounds were attributed to their binding to amino ac...
Article
Full-text available
Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are of interest to drug companies. These proteins kinase (PKs) are considered as validated drug targets. In cancer, proteins kinases play a key role in regulating numerous cellular functions including increased proliferation, decreased apoptosis, increased invasion, metastasi...
Article
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Small molecule tyrosine kinase inhibitors of the epidermal growth receptor (EGF-R) are of pharmaceutical interest because these proteins kinases (PKs) are considered validated drug targets. In cancer, protein tyrosine kinase plays a key role in regulating numerous cellular functions including increased proliferation, decreased apoptosis, increased...
Article
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Background: The tumor suppressor protein p53 plays an important role in preventing tumor formation and progression through its involvement in cell division control and initiation of apoptosis. Mdm2 protein controls the activity of p53 protein through working as ubiquitin E3 ligase promoting p53 degradation through the proteasome degradation pathwa...
Article
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A recent approach in cancer treatment is the angiogenesis inhibitors, as represented by the endothelial growth factor receptor inhibitors and vascular endothelial growth factor receptor inhibitors such as thalidomide and lenalidomide. We envision structural analogues to lenalidomide namely aminoacetylenic-2-methylindoline series as a novel and new...
Article
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Objective: The aim of this study was to design and synthesize new amino acetylenic 5-ethoxy-2-mercaptobenzimidazole derivatives as potential antimicrobial agents. Methods: New series of 5-ethoxy-2-{[4-(t-amino-1-yl) but-2-yn-1-yl] sulfanyl}-1H-benzimidazole derivatives were synthesized by Mannich reaction, and investigated for their antimicrobial a...
Article
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Obtaining false positives in enzyme inhibition assays is a common problem in early drug discovery, especially those compounds which form colloid aggregates in solution. The molecular basis of these aggregates could not be thoroughly explored because of their transient stability. Here, we conduct comparative MD simulations of miconazole, a strong ag...
Article
A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an efficient procedure. The antibacterial activity of the new compounds was studied against four bacterial strains. Compound 5 was found to exhibit the highest potency, with = 1.0 μg/ml, against both Escherichia coli and Pseudomonas aeruginosa when compared with amoxicillin...
Article
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Purpose: To perform a virtual screening for a set of drug-like ligand library against the Staphylococcus aureus enoyl acyl carrier protein reductase, saFabI. Methods: The virtual screening was conducted based on a previously validated pharmacophore-constrained docking. Consequently, the top list obtained was filtered using visual inspection where f...
Article
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p> Objective: To design and synthesise a new amino acetylenic tetrahydro phthalimide derivative and investigate their selective inhibitory activity to COXs. Methods: Aminoacetylenic tetrahydro phthalimide derivatives were synthesised by alkylation of tetrahydro phthalimide with propargyl bromide afforded 2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-...
Article
Pathogenic variants in theP21 protein (Cdc42/Rac)-activated kinase 3gene (PAK3) lead to a rare non syndromic X-linked intellectual disability. The protein encoded by this gene forms an activated complex with GTP-bound RAS-like (P21), CDC2 and RAC1 proteins which then mediates a variety of cellular processes. So far, mutations in PAK3 gene have been...
Article
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Protein tyrosine phosphatases (PTP) play important roles in the pathogenesis of many diseases. The fact that no PTP inhibitors have reached the market so far has raised many questions about their druggability. In this study, the active sites of 17 PTPs were characterized and assessed for its ability to bind drug-like molecules. Consequently, PTPs w...
Article
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Cell cycle is a highly coordinated and well conserved process and abrogation in the cell cycle are a hallmark of many types of cancer, thus, it has been under the spotlight as a target of anti-cancer therapeutics for decades. A wide range of tumor-associated mutations have been linked to abnormal regulation of protein kinases. MPS1 protein family i...
Conference Paper
Protein tyrosine phosphatases play important roles in the signalling system in our bodies and were observed to be overexpressed in many diseases. For instance, PTP1B, the most famous member of this family, has a well-established role in diabetes mellitus, obesity and cancer. However, no PTP inhibitors have reached the market so far. This raised a q...
Conference Paper
MDM2 is a protein that regulates the action of tumor suppressor protein P53. Inhibiting the interaction between the two proteins is widely considered in anti-cancer drug discovery approach. Targeting p53-bindig site on the MDM2 protein can be useful for the development of new anticancer agents. Several drugs with selective activity have been introd...
Article
Enoyl acyl carrier protein reductases (ENRs) have an important role in fatty acid biosynthesis and are considered essential for bacterial and protozoal survival. Here we perform a computational assessment of ENR structures, providing insights for inhibitor design that we incorporate into a virtual screening approach. Firstly we analyse 80 crystal s...
Article
Full-text available
Objective: To synthesize new amino acetylenic benzophenone derivatives with significant H3-antagonist's activity. Methods: Amino acetylenic benzophenone derivatives were synthesized from the reaction of 2-hydroxybenzophenone with 3-bromoprop-1-in to generate 2-(prop-2-yn-1-yloxy)-1,3-benzophenone (AZ-1). A mixture of 2-(prop-2-yn-1-yloxy)-1,3-benzo...
Article
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Paracetamol has an extensive first-pass metabolism that highly affects its bioavailability (BA); thus, dose may be repeated several times a day in order to have longer efficacy. However, hepatotoxicity may arise because of paracetamol metabolism. Therefore, this project aimed to increase paracetamol BA in rats by glucosamine (GlcN). At GlcN–paracet...
Article
Effects of the histamine H1 receptor (H1R) antagonists (antihistamines), promethazine (PMZ), orphenadrine (ORP), chlorpheniramine (CLP), pyrilamine (PYR), diphenhydramine (DPH), citerizine (CTZ), and triprolidine (TRP) on the functional properties of the cloned α7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes we...
Article
Full-text available
Aminoacetylenicoxybenzothiazole derivatives were synthesized from the reaction of 2-hydroxybenzothiazole with 3-bromoprop-1-yne to generate 2-(prop-2-ynl-1-yloxy)-1,3-benzothiazole (RM-1). A mixture of 2-(prop-2-yn-1-yloxy)-1,3-benzothiazole, paraformaldehyde, cyclic amine and cuprous chloride catalytic amount, in peroxide-free dioxane through Mann...
Article
Docking-based virtual screening is an established component of structure-based drug discovery. Nevertheless, scoring and ranking of computationally docked ligand libraries still suffer from many false positives. Identifying optimal docking parameters for a target protein prior to virtual screening can improve experimental hit rates. Here, we examin...
Article
The reported pharmacological activities of acetylenic and phthalimide groups promoted our interest to synthesize a novel series of N-[4-(t-amino-yl)-but-2-yn-1-yl] isoindoline-1,3-diones as anti-inflammatory compounds. The aim of this research is to investigate the selectivity of two compounds, ZM4 and ZM5, on inhibiting cyclooxygenase (COX) in vit...
Article
Full-text available
Elevated Src family kinase (SFK) activity is associated with tumor invasion and metastasis. The SFK inhibitor saracatinib (AZD0530) is currently in phase II trials in patients including those with colorectal cancer (CRC), where links between SFK activity and poor prognosis are particularly striking. Saracatinib is likely to be used clinically in co...

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