Papers by Mahmoud Ibrahim
In Silico Targeting Human Multidrug Transporter ABCG2 in Breast Cancer: Database Screening, Molecular Docking, and Molecular Dynamics Study
Molecular Informatics
ACS Omega
The versatility of the X-T-X 3 compounds (where T = C, Si, and Ge, and X = F, Cl, and Br) to part... more The versatility of the X-T-X 3 compounds (where T = C, Si, and Ge, and X = F, Cl, and Br) to participate in tetrel-and halogen-bonding interactions was settled out, at the MP2/aug-cc-pVTZ level of theory, within a series of configurations for (X-T-X 3) 2 homodimers. The electrostatic potential computations ensured the remarkable ability of the investigated X-T-X 3 monomers to participate in σ-hole halogen and tetrel interactions. The energetic findings significantly unveil the favorability of the tetrel•••tetrel directional configuration with considerable negative binding energies over tetrel•••halogen, type III halogen•••halogen, and type II halogen•••halogen analogs. Quantum theory of atoms in molecules and noncovalent interaction analyses were accomplished to disclose the nature of the tetrel-and halogen-bonding interactions within designed configurations, giving good correlations between the total electron densities and binding energies. Further insight into the binding energy physical meanings was invoked through using symmetry-adapted perturbation theory-based energy decomposition analysis, featuring the dispersion term as the most prominent force beyond the examined interactions. The theoretical results were supported by versatile crystal structures which were characterized by the same type of interactions. Presumably, the obtained findings would be considered as a solid underpinning for future supramolecular chemistry, materials science, and crystal engineering studies, as well as a fundamental linchpin for a better understanding of the biological activities of chemicals.
Molecules
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (Mpro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as Mpro inhibitors with ΔGbinding ≤ −40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhi...
Hyperkalemic Emergency: When You Have Taken a Few Too Many KCl Tablets
Cureus
RSC Advances
A solvent extract of the soft coral Sarcophyton ehrenbergi afforded cembrene diterpenoids, sarcoe... more A solvent extract of the soft coral Sarcophyton ehrenbergi afforded cembrene diterpenoids, sarcoehrenbergilid D–F (1–3).
A Computational Investigation of Unconventional Lone‐Pair Hole Interactions of Group V–VIII Elements
ChemistrySelect
Kaemgalangol A: Unusual seco-isopimarane diterpenoid from aromatic ginger Kaempferia galanga
Fitoterapia, 2018
A new unusual seco-isopimarane, kaemgalangol A (1) and 12 usual analogs (2-13) were isolated from... more A new unusual seco-isopimarane, kaemgalangol A (1) and 12 usual analogs (2-13) were isolated from the rhizomes of Kaempferia galanga (Family: Zingiberaceae). KaemgalangolA (1) represented a rarely isolated 9,10-seco-isopimarane skeleton. The chemical structures of the isolated compounds were mainlyinvestigated by spectroscopic techniques such as 1D, 2D NMR, and HRMS. The absolute configuration of 1-3 was studied by X-ray diffraction analysis as well as experimental and TDDFT-calculated electronic circular dichroism. Among the isolated diterpenoids, 5, 6 and 9 exhibited cytotoxic activity against HeLa (IC 75.1, 74.2 and 76.5 μM, respectively) and HSC-2 (IC 69.9, 53.3 and 58.2 μM, respectively) cancer cells.
Quantum-mechanical investigation of tetrel bond characteristics based on the point-of-charge (PoC) approach
Journal of molecular modeling, Jan 27, 2018
The point-of-charge (PoC) approach was employed to investigate the characteristics of the tetrel ... more The point-of-charge (PoC) approach was employed to investigate the characteristics of the tetrel bond from an electrostatic perspective. W-T-XYZ···B nomenclature was suggested where T is a tetrel atom, W is the atom along the σ-hole extension, B is a Lewis base, and X, Y, and Z are three atoms on the same side of the σ-hole. Quantum-mechanical calculations were carried out on F-T-F systems (where T = C, Si, Ge, or Sn) at the MP2/aug-cc-pVTZ level of theory, with PP functions for Ge and Sn atoms. The tetrel bond strength was estimated via the molecular stabilization energy. Tetrel bond strength was found to increase with increasing PoC negativity (i.e., Lewis basicity) and the electronegativity of the W atom. Moreover, the effects of the T···PoC distance, the W-T···PoC angle, and the aqueous medium on the tetrel bond strength were also investigated. Correlations between tetrel bond strength and several atomic and molecular descriptors such as the natural charge on the tetrel atom, E,...
Nature communications, Oct 26, 2018
Divergent transcription from promoters and enhancers is pervasive in many species, but it remains... more Divergent transcription from promoters and enhancers is pervasive in many species, but it remains unclear if it is a general feature of all eukaryotic cis regulatory elements. To address this, here we define cis regulatory elements in C. elegans, D. melanogaster and H. sapiens and investigate the determinants of their transcription directionality. In all three species, we find that divergent transcription is initiated from two separate core promoter sequences and promoter regions display competition between histone modifications on the + 1 and -1 nucleosomes. In contrast, promoter directionality, sequence composition surrounding promoters, and positional enrichment of chromatin states, are different across species. Integrative models of H3K4me3 levels and core promoter sequence are highly predictive of promoter and enhancer directionality and support two directional classes, skewed and balanced. The relative importance of features to these models are clearly distinct for promoters a...
Design, synthesis and biological evaluation of fused naphthofuro[3,2-c] quinoline-6,7,12-triones and pyrano[3,2-c]quinoline-6,7,8,13-tetraones derivatives as ERK inhibitors with efficacy in BRAF-mutant melanoma
Bioorganic chemistry, Jan 23, 2018
Approximately 60% of human cancers exhibit enhanced activity of ERK1 and ERK2, reflecting their m... more Approximately 60% of human cancers exhibit enhanced activity of ERK1 and ERK2, reflecting their multiple roles in tumor initiation and progression. Acquired drug resistance, especially mechanisms associated with the reactivation of the MAPK (RAF/MEK/ERK) pathway represent a major challenge to current treatments of melanoma and several other cancers. Recently, targeting ERK has evolved as a potentially attractive strategy to overcome this resistance. Herein, we report the design and synthesis of novel series of fused naphthofuro[3,2-c]quinoline-6,7,12-triones 3a-f and pyrano[3,2-c]quinoline-6,7,8,13-tetraones 5a,b and 6, as potential ERK inhibitors. New inhibitors were synthesized and identified by different spectroscopic techniques and X-ray crystallography. They were evaluated for their ability to inhibit ERK1/2 in an in vitro radioactive kinase assay. 3b and 6 inhibited ERK1 with IC50s of 0.5 and 0.19 µM, and inhibited ERK2 with IC50s of 0.6 and 0.16 µM respectively. Kinetic mecha...
Molecules (Basel, Switzerland), 2018
species are rich in diterpenes. A solvent extraction of , a species indigenous to the Southern Si... more species are rich in diterpenes. A solvent extraction of , a species indigenous to the Southern Sinai of Egypt, afforded several premyrsinane diterpenoids (⁻) as well as previously reported metabolites (⁻) that included three flavonoids. Isolated compounds were chemically characterized by spectroscopic analysis. Identified compounds were bioassayed for anti-proliferative activity in vitro against colon (Caco-2) and lung (A549) tumor cell lines. Compound exhibited robust anti-proliferative activity against A549 cells (IC = 3.3 µM). Absolute configurations for versus were determined by experimental and TDDFT-calculated electronic circular dichorism (ECD) spectra.
Lipids in health and disease, Jan 9, 2017
Although delayed cord clamping (DCC) is a recent WHO recommendation, early cord clamping (ECC) is... more Although delayed cord clamping (DCC) is a recent WHO recommendation, early cord clamping (ECC) is still a routine practice in many countries. Limited researches studied the effect of delayed cord clamping on oxidative stress in term neonates; In this study we aim to assess the influence of cord clamping either early or late on oxidative stress in term neonates and to evaluate the association of oxidative stress and cord blood lipids. One-hundred mothers and their term neonates were included in the present study. Umbilical cord blood samples were collected from the umbilical vein and umbilical artery immediately following labor. Total cholesterol, total triglycerides and phospholipids levels were significantly higher in the ECC group than the DCC group (p < 0.001 in all). Plasma total antioxidant status was higher in the DCC group than the ECC group (p < 0.001). While, plasma hydroperoxides were lower in the DCC group than the ECC group (p < 0.001). Levels of erythrocytes ca...
Synthesis, antiproliferative, anti-tubulin activity, and docking study of new 1,2,4-triazoles as potential combretastatin analogues
European journal of medicinal chemistry, Jan 28, 2017
Combretastatin A4 (CA4) is a natural product characterized by a powerful inhibition of tubulin po... more Combretastatin A4 (CA4) is a natural product characterized by a powerful inhibition of tubulin polymerization and a potential anticancer activity. However, therapeutic application of CA4 is substantially hindered due to geometric isomerization. In the current study, new cis-restricted Combretastatin A4 analogues containing 1,2,4-triazle in place of the olefinic bond were designed and synthesized. The synthesized compounds were evaluated for their in vitro antiproliferative activity in human hepatocellular carcinoma HepG2 and leukemia HL-60 cell lines using MTT assay. Moreover, fourteen compounds were selected and tested for their antiproliferative activity by the National Cancer Institute. Some of the tested compounds showed moderate activity against sixty cell lines. In vitro tubulin polymerization inhibitory activity was evaluated on HepG2 cells. The assay revealed that 6a showed a remarkable tubulin inhibition compared to CA4. Moreover, the cell cycle analysis revealed significan...
Marine drugs, Jan 21, 2017
Three new cembrene diterpenoids, sarcoehrenbergilid A-C (1-3), along with four known diterpenoids... more Three new cembrene diterpenoids, sarcoehrenbergilid A-C (1-3), along with four known diterpenoids, sarcophine (4), (+)-7α,8β-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were isolated and characterized from a solvent extract of the Red Sea soft coral Sarcophyton ehrenbergi. Chemical structures were elucidated by NMR and MS analyses with absolute stereochemistry determined by X-ray analysis. Since these isolated cembrene diterpenes contained 10 or more carbons in a large flexible ring, conformer stabilities were examined based on density functional theory calculations. Anti-proliferative activities for 1-8 were evaluated against three human tumor cell lines of different origins including the: lung (A549), colon (Caco-2), and liver (HepG2). Sardisterol (8) was the most potent of the metabolites isolated with an IC50 of 27.3 µM against the A549 cell line. Since an elevated human-cancer occurrence is associated with an aberran...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, Jul 27, 2016
Numerous randomized controlled trials (RCTs) demonstrated efficacy and safety of extracorporeal s... more Numerous randomized controlled trials (RCTs) demonstrated efficacy and safety of extracorporeal shock wave therapy (ESWT) for chronic plantar fasciopathy (cPF). However, only two such RCTs investigated a follow-up period of more than one year, both applying focused ESWT. Corresponding data for radial ESWT (rESWT) have not yet been reported. We therefore tested the hypothesis that rESWT is effective and safe for the management of cPF with long-term follow-up of two years. To this end n = 50 patients with cPF were randomly allocated to either two sessions of rESWT (one session per week; 2000 shock waves with energy flux density of 0.16 mJ/mm(2) per session) (n = 25) or to placebo treatment (n = 25). Evaluation was by change in Visual Analog Scale (VAS) score and Roles and Maudsley (RM) score. Mean pretreatment VAS scores for the rESWT and placebo groups were 8.5 and 8.9, respectively. One, three, six, 12 and 24 months after treatment, the mean VAS scores for the rESWT and placebo grou...
An investigation into the effect of electrostatic actuation and mechanical shock on microstructures
UMI, ProQuest ® Dissertations & Theses. The world's most comprehensive collection of dis... more UMI, ProQuest ® Dissertations & Theses. The world's most comprehensive collection of dissertations and theses. Learn more... ProQuest, An investigation into the effect of electrostatic actuation and mechanical shock on microstructures. ...
FEBS Journal, 2016
Genome-wide datasets measuring nascent RNA have revealed that active human promoters frequently d... more Genome-wide datasets measuring nascent RNA have revealed that active human promoters frequently display divergent transcription, generating a stable mRNA in the forward direction toward the gene and a typically unstable one in the reverse direction away from the gene. Recent work has shown that these transcripts originate from two distinct core promoters within a single nucleosome-free region (NFR). Different levels of forward and reverse activity lead to a wide range of directionality for promoter NFRs. Importantly, directionality is also reflected in the epigenetic modifications of nucleosomes immediately adjacent to the NFR. Here, we review the current literature pertaining to divergent transcription from promoter NFRs and its association with combinatorial histone post-translational modifications, or chromatin states, on upstream and downstream nucleosomes. Finally, we discuss several models to interpret the directionality of promoter chromatin states.
Genetics, 1961
HROMOSOMAL interchanges are exchanges of pieces between two non-' homologous chromosomes. The exc... more HROMOSOMAL interchanges are exchanges of pieces between two non-' homologous chromosomes. The exchanged pieces when they pair with their similar parts of the normal chromosomes during meiosis from a configuration of four chromosomes as a LLcross" in pachytene stages and as a ring in diakinesis. Following 2-2 segregation, alternate or adjacent chromosomes may pass to the same pole at the end of division I. When there is no crossing over in the interstitial segment (the part of the chromosome between the centromere and the interchange break point) , in alternate segregation the two interchanged chromo
Experimental & applied acarology, 2001
Two forms of the nymphal thrombin inhibitors (NTI) 3.2 kDa and 14.9 kDa were purified by chromato... more Two forms of the nymphal thrombin inhibitors (NTI) 3.2 kDa and 14.9 kDa were purified by chromatography on CM-cellulose. Sephacryl S-300 and Sephadex G-50 columns and designated NTI- 1 and NTI-2 respectively. The NTI-2 turned out to be homogenous monomeric protein in both native-PAGE and denatured SDS-PAGE with M(r) value of 14.9 kDa approximately and its pI value ranged from 7.2 to 7.5. The NTI-1 and NTI-2 displayed anticoagulant activity since they prolonged both the activated partial thromboplastin time (APTT) and the prothrombin time (PT) of the camel plasma in a concentration-dependent manner. The potency of NTI-I toward thrombin was 5-fold higher than that toward FXa, while NTI-2 was 3-fold active toward FXa than thrombin. However, both of them did not inhibit any of the other examined proteases. The types of inhibition of thrombin by NTI-1 and NTI-2 were non-competitive and competitive with inhibition constants (Ki) values of 11.7 microM and 211 nM respectively. One binding s...
Open and Contained Cold Aisle Experimentally Validated CFD Model Implementing CRAC and Server Fan Curves for a Data Center Test Laboratory
Volume 2: Thermal Management; Data Centers and Energy Efficient Electronic Systems, 2013
&quot;This paper presents the results of an experimentally validated Computational Fluid Dyna... more &quot;This paper presents the results of an experimentally validated Computational Fluid Dynamics (CFD) model for a data center with fully implemented fan curves on both the servers and the Computer Room Air Conditioner (CRAC). Open and contained cold aisle systems are considered experimentally and numerically. This work is divided into open (uncontained) cold aisle system calibration and validation, and fully contained cold aisle system calibration and leakage characterization. In the fully contained cold aisle system, a detailed containment CFD model based on experimental measurements is developed. The model is validated by comparing the flow rate through the perforated floor tiles with the experimental measurements. The CFD results are in a good agreement with the experimental data. The average error is about 6.7%. Temperature measurements are used to calibrate other sources of containment and racks leaks including mounting rails and clearance between racks. The temperature measurements and the CFD results agree well with average error less than 2%. Important conclusions can be drawn from this study. In order to accurately model the containment system, both the CRAC and the load banks fan curves should be simulated in the numerical model. Unavoidable racks and containment leaks could cause inlet temperature increase even if the cold aisle is overprovisioned with cold air. It is also noted that heat conduction through the floor tiles causes a slight increase the inlet temperature of the cold aisles. Finally, it is noteworthy that using detailed modeling is necessary to understand the details of the thermal systems, however simpler and faster to compute equivalent models can be used in extended optimization studies that show relative rankings of different designs.&quot;
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Papers by Mahmoud Ibrahim