Jihane Akachar - Academia.edu (original) (raw)

Papers by Jihane Akachar

Research paper thumbnail of Identifying epitopes for cluster of differentiation and design of new peptides inhibitors against human SARS-CoV-2 spike RBD by an in-silico approach

Research paper thumbnail of The displacement study of 99mTc‐DTPA—Human serum albumin binding in presence of furosemide and metformin by using equilibrium dialysis and molecular docking

IUBMB Life, 2019

The 99mTc‐DTPA (Technetium99m diethylenetriaminepentaacetic acid), is a radiopharmaceutical used ... more The 99mTc‐DTPA (Technetium99m diethylenetriaminepentaacetic acid), is a radiopharmaceutical used in renal scintigraphy. The human serum albumin (HSA) binding site(s) for the 99mTc‐DTPA have never been characterized. This study will cover in vitro the binding rates of 99mTc‐DTPA on HSA and the 99mTc‐DTPA competition interactions with two drugs having known human serum albumin binding sites. Furosemide (FUR) and metformin (MET) were added to 99mTc‐DTPA solution (weight ratios 1/1 vol:vol) followed by the quantification of 99mTc‐DTPA binding rates to HSA (40 g/L) using equilibrium dialysis and the qualification of this binding using Molecular Modeling methods. The 99mTc‐DTPA binding rates to human serum albumin increased with the highest concentration. Both drugs FUR and MET displaced 99mTc‐DTPA binding. 99mTc‐DTPA could bind to human serum albumin in many locations in site I and I‐II, but strongly bound to site I through hydrogen bonds.

Research paper thumbnail of In-silico identification of potential inhibitors targeting the DNA binding domain of estrogen receptor α for the treatment of hormone therapy-resistant breast cancer

Journal of biomolecular structure & dynamics, 2021

Estrogen receptor α (ERα) plays a critical role in breast cancer (BC) development. The standard t... more Estrogen receptor α (ERα) plays a critical role in breast cancer (BC) development. The standard therapeutic strategies for ERα- positive (ERα+) BC consist of impairing ERα signalling pathway by either estrogen competitors blocking its interaction with the ligand binding domain (LBD) or agents inhibiting the production of estrogen. These strategies are limited by many factors that lead to constitutive activation of ERα and consequently, resistance to treatment. Targeting the DNA binding domain (DBD) of ERα instead of its LBD with small-molecule inhibitors could be an alternative to impair ERα's signalling pathway. For this purpose, we conducted a structure based virtual screening of DrugBank against the crystal structure of ERα-DBD (PDB ID: 1HCQ) using the Glide module in standard precision (SP) and extra precision (XP) mode of docking. Molecules with XP Gscore less than -8 kcal/mol were selected and visually inspected to keep only the reasonable docking poses. Subsequently, thes...

Research paper thumbnail of In silico exploration of small-molecule α-helix mimetics as inhibitors of SARS-COV-2 attachment to ACE2

Journal of biomolecular structure & dynamics, 2020

The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than ... more The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than 502,539 deaths worldwide as of June 2020. The explosive spread of the virus and the rapid increase in the number of cases require the immediate development of effective therapies and vaccines as well as accurate diagnosis tools. The pathogenesis of the disease is triggered by the entry of SARS-CoV-2 via its spike protein into ACE2-bearing host cells, particularly pneumocytes, resulting in overactivation of the immune system, which attacks the infected cells and damages the lung tissue. The interaction of the SARS-CoV-2 receptor binding domain (RBD) with host cells is primarily mediated by the N-terminal helix of ACE2; thus, inhibition of the spike-ACE2 interaction may be a promising therapeutic strategy for blocking the virus entry into host cells. In this paper, we used an in-silico approach to explore small-molecule α-helix mimetics as inhibitors that may disrupt the attachment of SARS...

Research paper thumbnail of Synthesis, spectroscopic characterization, crystal structure, DFT studies and biological activities of new hydrazone derivative: 1-(2,5-bis((E)-4-isopropylbenzylidene)cyclopentylidene)-2-(2,4-dinitrophenyl) hydrazine

Journal of Molecular Structure, 2020

An aromatic α, β-unsaturated Ketone (2E,5E)-2,5 bis(4-isopropyl benzylidene) cyclopentanone (A) h... more An aromatic α, β-unsaturated Ketone (2E,5E)-2,5 bis(4-isopropyl benzylidene) cyclopentanone (A) have been achieved by a Claisen-Schmidt reaction. A new hydrazone derivative 1-(2,5-bis((E)-4-isopropyl benzylidene) cyclopentylidene)-2-(2,4-dinitrophenyl) hydrazine (B) was synthesized by reacting under reflux chalcone (A) with 2,4-dinitrophenylhydrazine and evaluated for its biological activities. The structure of the title compound (B) was studied using different spectroscopic techniques such as 1H and 13C NMR, FT-IR, UV–visible and confirmed by low-temperature single-crystal X-ray diffraction analysis. Complementary computation studies using DFT and TD-DFT at B3LYP reproduced well the experimental geometrical parameters and the spectroscopic properties. The obtained biological results revealed that the synthesized compound displayed higher antioxidant activity (IC50 = 6.95 ± 0.03 μM) in comparison to BHA and BHT standards by superoxide anion radical assay, and an interesting anti-tyr...

Research paper thumbnail of Identifying epitopes for cluster of differentiation and design of new peptides inhibitors against human SARS-CoV-2 spike RBD by an in-silico approach

The coronavirus disease 19 (COVID-19) is a highly contagious and rapidly spreading infection caus... more The coronavirus disease 19 (COVID-19) is a highly contagious and rapidly spreading infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In some cases, the disease can be fatal which resulted in more than one million deaths worldwide according the WHO. Currently, there is no effective vaccine or treatment for COVID-19, however many small-molecule inhibitors have shown potent antiviral activity against SARS-CoV-2 and some of them are now under clinical trials. Despite their promising activities, the development of these small molecules for the clinical use can be limited by many factors like the off-target effect, the poor stability, and the low bioavailability. The clusters of differentiation CD147, CD209, CD299 have been identified as essential entry co-receptors for SARS-CoV-2 species specificity to humans, although the underlying mechanisms are yet to be fully elucidated. In this paper, protein-protein docking was utilized for identifying the criti...

Research paper thumbnail of Design, synthesis, structural and molecular characterization, toxicity, psychotropic activity and molecular docking evaluation of a novel phenytoin derivative: 3-decyl-5,5-diphenylimidazolidine-2,4-dione

The hydantoin scaffold is of substantial importance and it is commonly used in drug discovery. He... more The hydantoin scaffold is of substantial importance and it is commonly used in drug discovery. Herein, we report the synthesis of a novel phenytoine (a hydantoin derivative) with high yield by the reaction of phenytoin with 1-bromodecyl agent. Namely, 3-decyl-5,5- diphenylimidazolidine-2,4-dione (3DDID). The optimized geometry of the compound was calculated using density functional theory (DFT) method by B3LYP with 6-311++G(d,p) basis set. For this calculation, the X-ray data were used as initial values. Molecular electrostatic potential (MEP) surface and Frontier molecular orbitals (FOMs) were prepared for the compound. The crystal structure of the title compound contains intermolecular N-H···O, C-H···O hydrogen bonds and weak C-H···π interactions. Hirshfeld surface analysis and 2D fingerprint plots of the molecule aid comparison of intermolecular interactions and these analysis reveals that two close contacts are associated with intermolecular hydrogen bonds. The psychotropic acti...

Research paper thumbnail of Three-dimensional Structure Prediction of the Human LMTK3 Catalytic Domain in DYG-in Conformation

Journal of Biomolecular Research & Therapeutics

Research paper thumbnail of In silico analysis of ACE2 orthologues to predict animal host range with high susceptibility to SARS-CoV-2

Research paper thumbnail of The Computational Analyses, Molecular Dynamics of Fatty-Acid Transport Mechanism to the CD36 Receptor: The Outcomes of the Mutation K164A on the Binding Domain, Structure and Function

The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the ele... more The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids. In this study, we used series of molecular dynamics simulations of the wild type and mutants types K164A CD36 protein interacting with one Palmitic acid (PLM) besides simulations of the wild type interacting with the three PLM to find out the mechanism of the functioning of the complex CD36/Fatty acids and the unraveling of the role of the mutation. Additionally we determined whether Lys164, mostly exposed to protein surface, played important roles in fatty acid uptake. These simulations revealed, the conformational changes induced by Lys164 residue and the altered interactions induced by the mutagenesis of surface lysine that was badly influencing the folding, utility, solubility, and stability form of the variant. Further...

Research paper thumbnail of Identifying epitopes for cluster of differentiation and design of new peptides inhibitors against human SARS-CoV-2 spike RBD by an in-silico approach

Research paper thumbnail of The displacement study of 99mTc‐DTPA—Human serum albumin binding in presence of furosemide and metformin by using equilibrium dialysis and molecular docking

IUBMB Life, 2019

The 99mTc‐DTPA (Technetium99m diethylenetriaminepentaacetic acid), is a radiopharmaceutical used ... more The 99mTc‐DTPA (Technetium99m diethylenetriaminepentaacetic acid), is a radiopharmaceutical used in renal scintigraphy. The human serum albumin (HSA) binding site(s) for the 99mTc‐DTPA have never been characterized. This study will cover in vitro the binding rates of 99mTc‐DTPA on HSA and the 99mTc‐DTPA competition interactions with two drugs having known human serum albumin binding sites. Furosemide (FUR) and metformin (MET) were added to 99mTc‐DTPA solution (weight ratios 1/1 vol:vol) followed by the quantification of 99mTc‐DTPA binding rates to HSA (40 g/L) using equilibrium dialysis and the qualification of this binding using Molecular Modeling methods. The 99mTc‐DTPA binding rates to human serum albumin increased with the highest concentration. Both drugs FUR and MET displaced 99mTc‐DTPA binding. 99mTc‐DTPA could bind to human serum albumin in many locations in site I and I‐II, but strongly bound to site I through hydrogen bonds.

Research paper thumbnail of In-silico identification of potential inhibitors targeting the DNA binding domain of estrogen receptor α for the treatment of hormone therapy-resistant breast cancer

Journal of biomolecular structure & dynamics, 2021

Estrogen receptor α (ERα) plays a critical role in breast cancer (BC) development. The standard t... more Estrogen receptor α (ERα) plays a critical role in breast cancer (BC) development. The standard therapeutic strategies for ERα- positive (ERα+) BC consist of impairing ERα signalling pathway by either estrogen competitors blocking its interaction with the ligand binding domain (LBD) or agents inhibiting the production of estrogen. These strategies are limited by many factors that lead to constitutive activation of ERα and consequently, resistance to treatment. Targeting the DNA binding domain (DBD) of ERα instead of its LBD with small-molecule inhibitors could be an alternative to impair ERα's signalling pathway. For this purpose, we conducted a structure based virtual screening of DrugBank against the crystal structure of ERα-DBD (PDB ID: 1HCQ) using the Glide module in standard precision (SP) and extra precision (XP) mode of docking. Molecules with XP Gscore less than -8 kcal/mol were selected and visually inspected to keep only the reasonable docking poses. Subsequently, thes...

Research paper thumbnail of In silico exploration of small-molecule α-helix mimetics as inhibitors of SARS-COV-2 attachment to ACE2

Journal of biomolecular structure & dynamics, 2020

The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than ... more The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than 502,539 deaths worldwide as of June 2020. The explosive spread of the virus and the rapid increase in the number of cases require the immediate development of effective therapies and vaccines as well as accurate diagnosis tools. The pathogenesis of the disease is triggered by the entry of SARS-CoV-2 via its spike protein into ACE2-bearing host cells, particularly pneumocytes, resulting in overactivation of the immune system, which attacks the infected cells and damages the lung tissue. The interaction of the SARS-CoV-2 receptor binding domain (RBD) with host cells is primarily mediated by the N-terminal helix of ACE2; thus, inhibition of the spike-ACE2 interaction may be a promising therapeutic strategy for blocking the virus entry into host cells. In this paper, we used an in-silico approach to explore small-molecule α-helix mimetics as inhibitors that may disrupt the attachment of SARS...

Research paper thumbnail of Synthesis, spectroscopic characterization, crystal structure, DFT studies and biological activities of new hydrazone derivative: 1-(2,5-bis((E)-4-isopropylbenzylidene)cyclopentylidene)-2-(2,4-dinitrophenyl) hydrazine

Journal of Molecular Structure, 2020

An aromatic α, β-unsaturated Ketone (2E,5E)-2,5 bis(4-isopropyl benzylidene) cyclopentanone (A) h... more An aromatic α, β-unsaturated Ketone (2E,5E)-2,5 bis(4-isopropyl benzylidene) cyclopentanone (A) have been achieved by a Claisen-Schmidt reaction. A new hydrazone derivative 1-(2,5-bis((E)-4-isopropyl benzylidene) cyclopentylidene)-2-(2,4-dinitrophenyl) hydrazine (B) was synthesized by reacting under reflux chalcone (A) with 2,4-dinitrophenylhydrazine and evaluated for its biological activities. The structure of the title compound (B) was studied using different spectroscopic techniques such as 1H and 13C NMR, FT-IR, UV–visible and confirmed by low-temperature single-crystal X-ray diffraction analysis. Complementary computation studies using DFT and TD-DFT at B3LYP reproduced well the experimental geometrical parameters and the spectroscopic properties. The obtained biological results revealed that the synthesized compound displayed higher antioxidant activity (IC50 = 6.95 ± 0.03 μM) in comparison to BHA and BHT standards by superoxide anion radical assay, and an interesting anti-tyr...

Research paper thumbnail of Identifying epitopes for cluster of differentiation and design of new peptides inhibitors against human SARS-CoV-2 spike RBD by an in-silico approach

The coronavirus disease 19 (COVID-19) is a highly contagious and rapidly spreading infection caus... more The coronavirus disease 19 (COVID-19) is a highly contagious and rapidly spreading infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In some cases, the disease can be fatal which resulted in more than one million deaths worldwide according the WHO. Currently, there is no effective vaccine or treatment for COVID-19, however many small-molecule inhibitors have shown potent antiviral activity against SARS-CoV-2 and some of them are now under clinical trials. Despite their promising activities, the development of these small molecules for the clinical use can be limited by many factors like the off-target effect, the poor stability, and the low bioavailability. The clusters of differentiation CD147, CD209, CD299 have been identified as essential entry co-receptors for SARS-CoV-2 species specificity to humans, although the underlying mechanisms are yet to be fully elucidated. In this paper, protein-protein docking was utilized for identifying the criti...

Research paper thumbnail of Design, synthesis, structural and molecular characterization, toxicity, psychotropic activity and molecular docking evaluation of a novel phenytoin derivative: 3-decyl-5,5-diphenylimidazolidine-2,4-dione

The hydantoin scaffold is of substantial importance and it is commonly used in drug discovery. He... more The hydantoin scaffold is of substantial importance and it is commonly used in drug discovery. Herein, we report the synthesis of a novel phenytoine (a hydantoin derivative) with high yield by the reaction of phenytoin with 1-bromodecyl agent. Namely, 3-decyl-5,5- diphenylimidazolidine-2,4-dione (3DDID). The optimized geometry of the compound was calculated using density functional theory (DFT) method by B3LYP with 6-311++G(d,p) basis set. For this calculation, the X-ray data were used as initial values. Molecular electrostatic potential (MEP) surface and Frontier molecular orbitals (FOMs) were prepared for the compound. The crystal structure of the title compound contains intermolecular N-H···O, C-H···O hydrogen bonds and weak C-H···π interactions. Hirshfeld surface analysis and 2D fingerprint plots of the molecule aid comparison of intermolecular interactions and these analysis reveals that two close contacts are associated with intermolecular hydrogen bonds. The psychotropic acti...

Research paper thumbnail of Three-dimensional Structure Prediction of the Human LMTK3 Catalytic Domain in DYG-in Conformation

Journal of Biomolecular Research & Therapeutics

Research paper thumbnail of In silico analysis of ACE2 orthologues to predict animal host range with high susceptibility to SARS-CoV-2

Research paper thumbnail of The Computational Analyses, Molecular Dynamics of Fatty-Acid Transport Mechanism to the CD36 Receptor: The Outcomes of the Mutation K164A on the Binding Domain, Structure and Function

The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the ele... more The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids. In this study, we used series of molecular dynamics simulations of the wild type and mutants types K164A CD36 protein interacting with one Palmitic acid (PLM) besides simulations of the wild type interacting with the three PLM to find out the mechanism of the functioning of the complex CD36/Fatty acids and the unraveling of the role of the mutation. Additionally we determined whether Lys164, mostly exposed to protein surface, played important roles in fatty acid uptake. These simulations revealed, the conformational changes induced by Lys164 residue and the altered interactions induced by the mutagenesis of surface lysine that was badly influencing the folding, utility, solubility, and stability form of the variant. Further...