Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
136,936
result(s) for
"Ibrahim"
Sort by:
Integrated study of Quercetin as a potent SARS-CoV-2 RdRp inhibitor: Binding interactions, MD simulations, and In vitro assays
To find an effective inhibitor for SARS-CoV-2, Quercetin’s chemical structure was compared to nine ligands associated with nine key SARS-CoV-2 proteins. It was found that Quercetin closely resembles Remdesivir, the co-crystallized ligand of RNA-dependent RNA polymerase (RdRp). This similarity was confirmed through flexible alignment experiments and molecular docking studies, which showed that both Quercetin and Remdesivir bind similarly to the active site of RdRp. Molecular dynamics (MD) simulations over a 200 ns trajectory, analyzing various factors like RMSD, RG, RMSF, SASA, and hydrogen bonding were conducted. These simulations gave detailed insights into the binding interactions of Quercetin with RdRp compared to Remdesivir. Further analyses, including MM-GBSA, Protein-Ligand Interaction Fingerprints (ProLIF) and Profile PLIP studies, confirmed the stability of Quercetin’s binding. Principal component analysis of trajectories (PCAT) provided insights into the coordinated movements within the systems studied. In vitro assays showed that Quercetin is highly effective in inhibiting RdRp, with an IC 50 of 122.1 ±5.46 nM, which is better than Remdesivir’s IC 50 of 21.62 ±2.81 μM. Moreover, Quercetin showed greater efficacy against SARS-CoV-2 In vitro , with an IC 50 of 1.149 μg/ml compared to Remdesivir’s 9.54 μg/ml. The selectivity index (SI) values highlighted Quercetin’s safety margin (SI: 791) over Remdesivir (SI: 6). In conclusion, our comprehensive study suggests that Quercetin is a promising candidate for further research as an inhibitor of SARS-CoV-2 RdRp, providing valuable insights for developing an effective anti-COVID-19 treatment.
Journal Article
Melatonin Mitigates Drought Induced Oxidative Stress in Potato Plants through Modulation of Osmolytes, Sugar Metabolism, ABA Homeostasis and Antioxidant Enzymes
The effect of melatonin (MT) on potato plants under drought stress is still unclear in the available literature. Here, we studied the effect of MT as a foliar application at 0, 0.05, 0.1, and 0.2 mM on potato plants grown under well-watered and drought stressed conditions during the most critical period of early tuberization stage. The results indicated that under drought stress conditions, exogenous MT significantly (p ≤ 0.05) improved shoot fresh weight, shoot dry weight, chlorophyll (Chl; a, b and a + b), leaf relative water content (RWC), free amino acids (FAA), non-reducing sugars, total soluble sugars, cell membrane stability index, superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (G-POX), and ascorbate peroxidase (APX) compared to the untreated plants. Meanwhile, carotenoids, proline, methylglyoxal (MG), H2O2, lipid peroxidation (malondialdehyde; MDA) and abscisic acid (ABA) were significantly decreased compared to the untreated plants. These responses may reveal the protective role of MT against drought induced carbonyl/oxidative stress and enhancing the antioxidative defense systems. Furthermore, tuber yield was differentially responded to MT treatments under well-watered and drought stressed conditions. Since, applied-MT led to an obvious decrease in tuber yield under well-watered conditions. In contrast, under drought conditions, tuber yield was substantially increased by MT-treatments up to 0.1 mM. These results may imply that under water deficiency, MT can regulate the tuberization process in potato plants by hindering ABA transport from the root to shoot system, on the one hand, and by increasing the non-reducing sugars on the other hand.
Journal Article
Anticancer derivative of the natural alkaloid, theobromine, inhibiting EGFR protein: Computer-aided drug discovery approach
A new semisynthetic derivative of the natural alkaloid, theobromine, has been designed as a lead antiangiogenic compound targeting the EGFR protein. The designed compound is an ( m -tolyl)acetamide theobromine derivative, ( T-1-MTA ). Molecular Docking studies have shown a great potential for T-1-MTA to bind to EGFR. MD studies (100 ns) verified the proposed binding. By MM-GBSA analysis, the exact binding with optimal energy of T-1-MTA was also identified. Then, DFT calculations were performed to identify the stability, reactivity, electrostatic potential, and total electron density of T-1-MTA . Furthermore, ADMET analysis indicated the T-1-MTA ’s general likeness and safety. Accordingly, T-1-MTA has been synthesized to be examined in vitro . Intriguingly, T-1-MTA inhibited the EGFR protein with an IC 50 value of 22.89 nM and demonstrated cytotoxic activities against the two cancer cell lines, A549, and HCT-116, with IC 50 values of 22.49, and 24.97 μM, respectively. Interestingly, T-1-MTA ’s IC 50 against the normal cell lines, WI-38, was very high (55.14 μM) indicating high selectivity degrees of 2.4 and 2.2, respectively. Furthermore, the flow cytometry analysis of A549 treated with T-1-MTA showed significantly increased ratios of early apoptosis (from 0.07% to 21.24%) as well as late apoptosis (from 0.73% to 37.97%).
Journal Article
Aotaphenazine, a rare hydrophenazine, targets topoisomerase II with anticancer efficacy: In silico to in vitro evidence
Topoisomerase II (Topo II) remains a validated target for anticancer therapy, with many clinically used agents acting via DNA intercalation and enzyme inhibition. However, their clinical use is limited by severe toxicity and resistance. In this study, we investigate aotaphenazine, a rare hydrophenazine derivative isolated from Streptomyces sp. IFM 11694 as a potential novel Topo II inhibitor with selective anticancer activity.
Molecular docking and 400 ns molecular dynamics (MD) simulations were employed to evaluate aotaphenazine's binding mode within the DNA-Topo II complex (PDB: 3QX3). MM-GBSA calculations quantified interaction energetics, while ProLIF and PLIP analyses detailed the interaction patterns. Topo II inhibition was assessed via in vitro enzymatic assays. Cytotoxicity (MTT) assays were conducted against a panel of human cancer and normal cell lines. Flow cytometry was used to evaluate apoptosis and cell cycle progression in MDA-MB-231 cells.
aotaphenazine demonstrated a docking binding energy of -19.12 kcal/mol and remained stably intercalated within the DNA groove during MD simulations. MM-GBSA analysis showed a total binding free energy of -29.81 kcal/mol, driven primarily by van der Waals forces. Interaction profiling identified consistent π-stacking with Cyt8 and Thy9, and strong binding contributions from Ade12 and Gua13. Enzymatic assays confirmed Topo II inhibition with an IC50 of 45.01 nM, comparable to doxorubicin (30.16 nM). In vitro cytotoxicity analysis revealed moderate activity across cancer cell lines (IC50 = 26.30-54.35 µM) and significantly reduced toxicity in normal WI-38 and WISH cells (IC50 = 69.86 µM and 84.72 µM, respectively). Flow cytometry showed that aotaphenazine induced early (20.98%) and late apoptosis (42.80%), along with S-phase cell cycle arrest (43.99%) and a marked reduction in the G2/M population in MDA-MB-231 cells.
aotaphenazine exhibits a compelling combination of Topo II inhibition, DNA intercalation, and selective anticancer activity, supported by both computational modeling and biological validation. Its lower cytotoxicity toward normal cells and ability to induce apoptosis and cell cycle arrest suggest strong therapeutic potential. These findings establish aotaphenazine as a promising lead compound for the development of safer and more selective Topo II-targeting anticancer agents.
Journal Article
Sword and scimitar : fourteen centuries of war between Islam and the west
A sweeping history of the often-violent conflict between Islam and the West, shedding a revealing light on current hostilities The West and Islam--the sword and the scimitar--have clashed since the mid-seventh century, when, according to Muslim tradition, the Byzantine emperor rejected Prophet Muhammad's order to abandon Christianity and convert to Islam, unleashing a centuries-long jihad on Christendom. Sword and Scimitar chronicles the significant battles that arose from this ages-old Islamic jihad, beginning with the first major Islamic attack on Christian land in 636, through the occupation of the Middle East that prompted the Crusades and the far-flung conquests of the Ottoman Turks, to the European colonization of the Muslim world in the 1800s, when Islam largely went on the retreat--until its reemergence in recent times. Using original sources in Arabic, Greek, Latin, and Turkish, preeminent historian Raymond Ibrahim describes each battle in vivid detail and explains the effect the outcome had on larger historical currents of the age and how the military lessons of the battle reflect the cultural faultlines between Islam and the West. The majority of these landmark battles are now forgotten or considered inconsequential. Yet today, as the West faces a resurgence of this enduring Islamic jihad, Sword and Scimitar provides the needed historical context to understand the current relationship between the West and the Islamic world, and why the Islamic State is merely the latest chapter of an old history.
Book
Design, Synthesis, Docking, DFT, MD Simulation Studies of a New Nicotinamide-Based Derivative: In Vitro Anticancer and VEGFR-2 Inhibitory Effects
A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact with the VEGFR-2 catalytic pocket. The ability of the designed congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, to bind with the VEGFR-2 enzyme was demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established the excellent binding of compound 10 with VEGFR-2 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed the proper binding with a total exact binding energy of −38.36 Kcal/Mol. MM-GBSA studies also revealed the crucial amino acids in the binding through the free binding energy decomposition and declared the interactions variation of compound 10 inside VEGFR-2 via the Protein–Ligand Interaction Profiler (PLIP). Being new, its molecular structure was optimized by DFT. The DFT studies also confirmed the binding mode of compound 10 with the VEGFR-2. ADMET (in silico) profiling indicated the examined compound’s acceptable range of drug-likeness. The designed compound was synthesized through the condensation of N-(4-(hydrazinecarbonyl)phenyl)benzamide with N-(4-acetylphenyl)nicotinamide, where the carbonyl group has been replaced by an imine group. The in-vitro studies were consonant with the obtained in silico results as compound 10 prohibited VEGFR-2 with an IC50 value of 51 nM. Compound 10 also showed antiproliferative effects against MCF-7 and HCT 116 cancer cell lines with IC50 values of 8.25 and 6.48 μM, revealing magnificent selectivity indexes of 12.89 and 16.41, respectively.
Journal Article