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Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, started in Wuhan, China in December 2019 and became a global pandemic. According to WHO, more than fourteen million cases were reported and thousands of casualties worldwide (until July 18, 2020). Most of the COVID-19 patients have symptoms such as fever, tiredness, and dry cough. Some people may also experience body aches, nasal congestion, a runny nose, and diarrhea. So far, doctors have been using treatment to relieve symptoms and give patients' immune systems time to regain control of this virus. Many studies have highlighted the important role of cytokine cascades in the death rate in COVID-19 patients. Therefore, inhibition of this phenomenon has become a very important target in the clinical management of this disease. With this idea, in this mini-review, we will focus on the potential role of cannabinoids in the suppression of cytokines cascades in patients with COVID-19 and their importance in the clinical management of this disease.

In search of new high-performance materials to be used in organic solar cells by changing the bridge of molecules already synthesized, we used the functional density theory (DFT) and Time-dependent density-functional theory (TD/DFT) with several methods such as B3LYP, PBEPBE, B3PW91, mPW1PW91 and the basic set 6-31G (d, p), the electronic structures and optoelectronic properties of four organic dyes based on 2-(6-substituted-anthracen-2-yl)-thiophene as the π conjugated bridge, different amines as electron donors, and cyanoacrylic acid group as an electron acceptor have been calculated and discussed theoretically in the aim to obtain the most suitable method. The calculated electronic levels HOMO, LUMO, and Egap of the studied compounds show that the B3LYP method with the 6-31G base set (d, p) offers better performances such as lower energy gap. Then, we studied the influence of the change of bridge (anthracene) by thiophene and benzene on the electronic, optical and photovoltaic properties of these organic dyes.TD-B3LYP functional was used to describe optoelectronic properties such as the UV–visible spectrum for the various compounds studied. Furthermore, the free energy of electron injection (ΔG inject), LHE and O.S were calculated and analyzed. In conclusion, the calculated results reveal that the new compounds studied can be used as good candidates for dye-sensitized solar cells (DSSC) due to its best electronic and optical properties and good photovoltaic parameters except for compound M3..

A new class of benzimidazoles bearing bis-Schiff bases as α-glucosidase inhibitory was studied based on the combination of two computational techniques such as 3D-QSAR and molecular docking. The CoMFA and CoMSIA QSAR models were developed from fifteen compounds in the training set and four compounds in the test set giving Q2 values of 0.587 and 0.597 respectively, and R2 values of 0.970 and 0.990 respectively. The adapted alignment method with the suitable parameters resulted in reliable models. The CoMFA and CoMSIA contour maps allowed the authors to recognize regions where the activity can be increased or decreased by suitable substitutions. According to these contour maps they have proposed three new compounds with high predicted activities. Moreover, to confirm the stability of these newly designed molecules in the receptor with PDB: 3A4A, a Surflex-docking was applied.

Acarbose and voglibose are α -glucosidase inhibitors that have been used for controlling of diabetes mellitus. Unfortunately, these drugs have many side effects. Consequently, the discovery of new agents with high α -glucosidase inhibitory activity and weak side effects becomes of great importance. To that end, a set of 23 benzothiazole compounds have been studied using 3D-QSAR modeling and molecular docking simulation in order to predict new molecules with important α -glucosidase inhibitory activity. CoMFA and CoMSIA models using eighteen compounds in the training set give significant Q2 values of 0.553 and 0.75, and important R2 values of 0.93 and 0.942, respectively. The five remaining molecules wereemployed in order to test the proficiency of 3D-QSAR models and the predicted determination coefficients R2test values are 0.74 and 0.87 for CoMFA and CoMSIA models, respectively. CoMFA and CoMSIA contour maps were afforded much helpful information to determine the preferred and unpreferred regions impacting the activity; as a result, we propose new benzothiazole compounds with important predicted activities. Meanwhile, to guess the interaction between a newly designed compounds and the most active molecule (compound 8) with α-glucosidase receptor (PDB ID: 3L4T), a molecular docking was conducted. The docking outcomes elucidated that the predicted compound X1 was stable in the active pocket of α-glucosidase receptor. Finally, the newly benzothiazole compounds have been assessed for their oral bioavailability and toxicity using ADMET properties and drug likeness. These findings would be of great aid in leading optimization for new drug discovery that can resolve the biggest challenge related of diabetes mellitus.

In the present paper, four π-conjugated materials, based on terphenyl and pyrrole, with A–D–A structure have been theoretically studied to propose new organic compounds to be used in the organic solar cell field. Moreover, the geometrical and optoelectronic properties of the designed molecules M1, M2, M3 and M4 have been computed after optimization in their fundamental states, using the quantum chemical method DFT / B3LYP/ 6−311G (d, p). Different parameters including HOMO and LUMO energy levels, bandgap energy, frontier molecular orbital (FMO), chemical reactivity indices, the density of states (DOS), Voc, electrostatic potential (ESP), and thermodynamic parameters at several temperatures in the range of 0-500 K have been determined. The absorption properties including the transition energy, the wavelengths (λmax), the excitation vertical energy, and the corresponding oscillator strengths of these molecules have been studied using the quantum chemical method TD−DFT / CAM–B3LYP / 6–311G (d, p). The obtained results of our studied compounds show that M3 (with 2H, 2'H-1, 1'-biisoindole moiety) as a donor group has special optoelectronic, absorption, and good photovoltaic characteristics. Thus, they can be utilized as an electron-donating in organic solar cells BHJ type.

The World Health Organization (WHO) considers cancer as the deadliest disease, due to the increase in death in the 21 century. In the search for new therapeutic molecules, the scientific researches consider the proviral integration moloney (Pim) kinases as promising therapeutic targets for the treatment of hematological cancers. A series of thirty-four 3,5-disubstituted indole derivatives as potent Pim1 kinase inhibitors were studied using 3D-QSAR (CoMFA and CoMSIA) and molecular docking. CoMFA analysis showed Q2 value of 0.56, R2 value of 0.86 and rtest2 value of 0.78, while CoMSIA analysis showed a Q2 value of 0.73, R2 value of 0.93 and rtest2 value of 0.80. The models were generated using 28 compounds as training set and 6 compounds as test set. Furthermore, the contour maps acquired from the CoMSIA and CoMFA models were used to rationalize the principal structural requirement responsible for the activity. As results, four new compounds were designed in silico. Furthermore, the newly designed compound X1 and the most active compound 28 were subjected to molecular docking study in order to validate their stability. Molecule docking shows that compound X1 has greater stability than compound 28. The newly compounds were evaluated for in silico toxicity properties and verified the five Lipinski rules for wet-lab applicability.

In this work, a theoretical study of π-conjugated materials based on diphenyl-diketopyrrolo-pyrrole is presented with the aim of proposing new organic materials for BHJ solar cells. Moreover, four compounds M1, M2, M3 and M4 have been reported. The geometric and electronic properties for these studied compounds are calculated after optimization in their fundamental states with DFT / B3LYP / 6 − 311G (d, p). Using this method, several parameters such as frontier molecular orbital, the HOMO and LUMO energies levels, the bandgap, chemical reactivity indices, the Voc and molecular electrostatic potential (MEP) have been discussed. The optical properties such as the transition energy, the wavelengths (λmax), the excitation vertical energy and the corresponding oscillator strengths have been carried out at the ground-state geometries using the TD − DFT method at CAM–B3LYP/6–311G (d, p). This investigation has been used to carry out the next synthesis to compounds more effective as active materials in optoelectronic.

A forty-two compounds series of potential epidermal growth factor receptor kinase inhibitors of Pyrazole derivatives containing thiourea analogs have been subjected to 3D-QSAR (3-Dimensional Quantitative Structural-Activity Relationship) studies using CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis). The training set and the test set of pyrazole derivatives have been used for the generation and validation of QSAR model, respectively. Dataset alignment has been performed using the lowest energy conformer of the most active compound. The best-generated CoMFA and CoMSIA models exhibit conventional determination coefficients R2 of 0.982 and 0.980 as well as the Leave One Out cross validation determination coefficients Q2 of 0.734 and 0.801, respectively. Moreover, the predictive ability of those models was evaluated by the external validation using a test set of five compounds with predicted determination coefficients R2test of 0.932 and 0.846, respectively. Based on those satisfactory results, ten new compounds have been designed and predicted by in silico Drug likeness and ADMET method. In addition, molecular docking studies were carried out to explore the binding interactions of the selected compounds with the enzyme. This study could expand the understanding of pyrazole derivatives as anti-cancer agent and would be of great help in lead optimization for early drug discovery of highly potent anticancer activity.

New therapeutic strategies, called targeted therapies, are now possible thanks to recent advances in oncology. These treatments more specifically reach cancer cells by disrupting the biological mechanisms that lead to their multiplication: they essentially act at the level of growth factor receptors. Tyrosine kinase inhibitors are small molecules that act specifically inside tumor cells by blocking the activation of tyrosine kinases. They are part of the new generation of anti-cancer drugs called targeted therapies. Using the tools of theoretical chemistry and drug design techniques, we constructed a structure–activity relationship model (3D-QSAR) based on the pharmacophore of a series of 9H-purine derivatives taken from the literature, whose EGFR inhibitors are quantitatively known. The QSAR model obtained, which is statistically satisfactory, will be used, on the one hand, to study the structural characteristics responsible for EGFR inhibition and, on the other hand, to predict structures of the same chemical family having a better activity on this protein kinase. We then performed the molecular docking protocol on the molecules considered relevant due to their activity on EGFR. This study aims to enrich the interpretations extracted from the contour maps of the 3D-QSAR model and to search in silico for the most favorable mode of interaction of these inhibitors within the receptor (PDB: 5XGN). The theoretical approaches used in our research should help to better understand the mechanisms involved in the ligand/receptor interaction and, ultimately, to rationalize the design of new molecules for therapeutic purposes. Post-print / Final draft

Monoamine oxidase-B (MAO-B) is a flavin-dependent enzyme involved in various neurodegenerative disorders. Here, a dataset of 142 chalcone derivatives, collected from various natural plants, was screened by combining structure-based virtual screening and ADMET approaches. The goal is to discover novel natural chalcones as potential MAO-B inhibitors. With the help of the Gaussian 09.5 software, the 3D chemical structures of compounds were optimized using the DFT method. The 3D structure of the hMAO-B enzyme was built using the Modeller software. The optimized structures were subjected to virtual screening by Autodock Vina, implicated in PyRx software. Among the 142 natural substances, 43 were selected based on their binding affinity. Then, the pharmacokinetic proprieties and toxicity of these compounds were evaluated using ADMET analysis. Ten compounds were predicted to have ADMET characteristics with no side effects. The binding modes and interactions of the top selected compounds were then evaluated using AutoDock 4.2. Compounds P60 and P81 were found to be potential inhibitors of MAO-B compared to rasagiline, safinamid, and selegiline, the reference drugs. The stability of the selected compounds was confirmed by MD simulation. Based on this finding, compounds P60 and P81 could be considered potential hMAO-B inhibitors.

In this study, quantitative mathematical models were established to understand the relationship between a series of 26 quinazoline / quinoline derivative and their biological activity against DENV virus using 3D-QSAR and HQSAR analysis. According to the results we obtained, the models have good predictability:the HQSAR model (Q 2 = 0.82, R 2 = 0.95), the CoMFA model with Q 2 = 0.755, R 2 = 0.94 and CoMSIA with Q 2 = 0.76, R 2 = 0.930. It should be noted that all three models successfully meet all external validation criteria. Molecular docking and dynamic simulation have been employed to explain the mode of binding between the ligand and the active site of the protein, and assess, justify ligand stability in the active receptor site respectively. The results of this research provide an information base for discovering new inhibitors of DENV virus.

In search of novel and more potent p-aminobenzoic acid derivatives previously evaluated as effective acetylcholinesterase inhibitors for the control of Alzheimer’s disease (AD), an integrated computational approach of three-dimensional quantitative structure–activity relationship and molecular docking were performed on a series of 20 compounds. The 3D-QSAR approach was applied to statistically study the structure-activity relationships (SAR) and had yielded good statistical significance for two high predictive models; comparative molecular field analysis (CoMFA: Q2=0.785; R2=0.936; rext2= 0.818) and comparative molecular similarity indices analysis (CoMSIA: Q2=0.831; R2=0.944; rext2= 0.931). Detailed analysis of the predictive models contour maps revealed that the hydrophobic and electrostatic fields govern the bioactivity and provided much helpful information to understand the features requirement in order to develop new potent acetylcholinesterase inhibitors. These findings were very useful for designing four novel inhibitors with enhanced activities targeting acetylcholinesterase. Through molecular docking, the newly designed compounds and compound 19 were docked on AChE as the protein target which helped to analyze the interaction characteristics and explore the binding modes at the active sites of the AChE. This work may be of utility for guiding the rational design of a new generation of acetylcholinesterase inhibitors. DOI: http://dx.doi.org/10.17807/orbital.v12i4.1467

The main objective of this study is to develop 2D- and 3D-QSAR statistical models for a series consisting of 28 molecules. The authors started with a 2D study based on principal component analysis (PCA), multiple linear regression (RLM), and nonlinear regression (RNLM). The models were developed using 28 molecules with a pIC50 between 5.70 and 6.70. Then they applied 3D-QSAR analysis based on the partial least squares (PLS) method. For 3D-QSAR, they used the molecular field comparative analysis (CoMFA) and comparative molecular similarity index (CoMSIA) methods. For this analysis, they have worked on a training set of 24 compounds, which then give acceptable and reliable values of Q2 (0.791 and 0.538, respectively) and R2 (0.974 and 0.98, respectively). To determine the quantitative 3D-QSAR, the interpretations were based on the contour maps which are produced by the CoMFA and CoMSIA models. In addition, molecular docking is also one of the most important methods for confirming the binding interactions of predicted molecules with their receptors.

The α-amylase is an enzyme of a highly conserved glycoside hydrolase family, α-amylase inhibitors can be used as clinical agents for the treatment of Diabetes Mellitus (DM). A 3D-QSAR study was performed on 45 2-aryl benzimidazole derivatives, which have been identified as insulin-independent antidiabetic agents. The 3D-QSAR technique includes CoMFA with Q2 of 0.696 and R2 of 0.860 and CoMSIA with Q2 of 0.514 and R2 of 0.852. Both models were derived from a training set of 37 compounds based on an appropriate method of alignment, while the predictive ability was approved by a test set containing 8 compounds with rext2 values of 0.990 and 0.987, respectively. Moreover, contour maps generated from CoMFA and CoMSIA models provided much helpful information to figure out the features requirements that have control over the activity. To further reinforce the 3D-QSAR results, the molecular docking method was implemented which led to design new potent insulin-independent antidiabetic compounds with high predicted activity values.

The objective of this work was the molecular modelling by bio-isostery of 2-chloroethylnitrosoureas CENU into 2-chloroethylnitrososulfamides CENS derived from Carmustine. We evaluated the pharmacodynamic profile of the new chemical class by studying molecular docking using innovative software. Good molecular docking scores were obtained through Auto-dock vina of the PyRx 0.8 software, the energy of the complexes formed (Target-Ligand) during the interaction varies from - 5,400 to -5,700 Kcal/mol, the total average between the 45 conformers is -5,213 Kcal/mol. The results were validated by Auto-dock vina 1.5.6 in collaboration with the Molecular Chemistry and Natural Substances Laboratory at the Meknes Faculty of Science - Morocco, a range of -4,900 to -5,100 Kcal/mol was noted for CENS complexes derived from Carmustine with the 2DND target, reflecting a better CENS chemical affinity to the biological target and the stability of the ligand-DNA complex, compared with the analogue reference Carmustine with a score of - 4,700 Kcal/mol. By superimposing the results of molecular docking, analysis of data from the study of electrophilia based on load transfer ECT and publications on CENS, we can predict that inter-strand crosslink is likely to occur between the Guanine dG22 of strand B and the Cytosine dC3 of strand A, located in the poly dA-poly dT segment end within the narrow minor groove of the DNA target (2DND). The molecular docking study was a preliminary approach to understand the therapeutic mode of action of CENS.Communicated by Ramaswamy H. Sarma.

The identification of chemotherapeutic drugs against Novel Coronavirus (2019-nCoV) is a significant requirement due to the rapid rise in deaths due to Corona Viral Infection all around the world. Therefore, it is of interest to document the molecular docking analysis data of 32 N-substituted Oseltamivir derivatives inhibitors of influenza virus H5N1 with the Novel Coronavirus main protease (2019-nCoV). We describe the optimal binding features of Oseltamivir derivatives with the SARS-Cov-2 main protease (Code PDB: 6LU7) for further consideration.

A theoretical study on four organic dyes based on bis(4-hexyloxy)triphenylamine as donor and electron acceptor cyanoacrylic acid with a donor–π–acceptor structure (D–π–(D–A–)–A) using DFT/DFT (TD-DFT)/6-31G(d,p) having a difference of π spacer was designed. The theoretical study of the structural, electronic and optical properties of these dyes (D1, D4) suggests that these materials would be excellent sensitizers as a candidate for the production of dye solar cells, due to the efficient photoinduced electron transfer and strong absorption as well as the electronic properties (HOMO, LUMO, Egap) low band gap, The improved light-harvesting efficiency and free energy change of electron injection (ΔGinject), of new designed sensitizers revealed that these materials would be excellent sensitizers. This theoretical designing paves the way for experimentalists to synthesize more efficient sensitizers for solar cells.

In this work, conjugated polymers based on thiophene: polythiophene, poly (3-alkythiophene) and poly (alkylbithiophene) were characterized using the nuclear magnetic resonance (NMR) and UV spectroscopy to determine their spectroscopic properties. Then, their structural, electronic and vibrational properties were investigated using the density functional theory (DFT) calculations by the oligomeric approach. The optoelectronic properties were assessed, as well. The obtained results were discussed basing on the influence of substitution on the properties of the oligomers. The possibility of thiophene based oligomers photovoltaic application was also studied. We have shown that the octithiophene (8T) its derivatives have a very good conversion rate and it serves as a candidate for the photovoltaic application.

Oncogenic Kirsten RAt Sarcoma (KRAS) mutations are attractive targets in non-small-cell lung cancer (NSCLC). Thus, the objective of this work is to discover promising inhibitors that target this protein using

In silico modelling studies were executed on thirty two N-substituted oseltamivir derivatives as inhibitors of influenza virus H5N1. Robust validated quantitative structure–activity relationship (QSAR) approaches have been investigated to explore the important structural requirements essential to design potent anti-influenza virus H5N1 inhibitors. Density functional theory (DFT) calculations with the Becke three-parameter Lee–Yang–Parr B3LYP hybrid functional employing the 6-31G(d) basis set are used to calculate quantum chemical descriptors. The dataset was randomly divided into training and test sets comprising 25 and 7 compounds, respectively. Twenty models were established by changing the compounds of the sets and further were applied to calculate the predicted pIC50 values of the 7 compounds in the test set. All constructed models were individually validated internally as well as externally along with y-randomization according to the OECD principles for QSAR model validation and Golbraikh and Tropsha's criteria of model acceptance. Model 5 is selected with higher R2, Rtest2 and Qcv2 values (R2 = 0.902, Radj2 = 0.888, MSE = 0.094, Rtest2 = 0.872, Qcv2 = 0.857). It is very interesting to find that the anti-influenza H5N1 activity of these compounds appears to be mainly governed by three molecular descriptors, i.e. the lowest unoccupied molecular orbital energy (ELUMO), the energy of the molecular orbital below the HOMO (EHOMO−1) and the number of atoms (NA). Here the possible mechanism of action of these compounds was analysed and discussed; in particular, important structural requirements for enhanced H5N1 virus inhibitor activity could be reached by reducing the molecular size and introducing stronger electron accepting ability groups with small atoms and more protons into the N-substituted oseltamivir derivatives. Based on the best proposed QSAR model, some new compounds with higher neuraminidase inhibitor activity have been theoretically designed. Such results can offer useful theoretical references for future experimental work.

This work proposes a theoretical study of the geometric and optoelectronic properties of some dendritic macromolecules consisting mainly of thiophene and carbazole. First, calculations were performed on a basic molecule called G2TTPG2 3T using the density functional theory (DFT) and varying between 5 different quantum methods to be able to choose the most appropriate which will then be applied to the derivatives of this molecule during the rest of this work, these derivatives were obtained by grafting the following groups: CN, EDOT-S, OH, OHOH, EDOT, F. The objective of this work is to study the effect of this chemical modification, better explore the structure-property relationship and also to search for compounds with the best optoelectronic properties in order to present them for synthesis. The results obtained reveal that the substitution by some groups has reduced the energy of the gap, decreased inter-cyclic distances and increased the value of the open circuit voltage.

The p53 is a tumor suppressor protein that adjusts cell cycle and growth arrest as well as genes that restore DNA damage and apoptosis. Murine double minute 2 (MDM2) is a main p53 antagonist. We created a novel QSAR model using a series of highly active spiro [pyrrolidin-3,2-oxindoles] that consisted of 29 compounds that were experimentally validated to inhibit the MDM2-p53 interaction. Three optimal models have been developed CoMFA/E+S, CoMSIA/S+H+A and HQSAR have revealed good statistical results, but the CoMSIA mode only which validates all the external validation tests applied successfully. Based on the CoMSIA/S+H+A model was carefully chosen to design four compounds with values ​​of inhibitory activity greater than the highly active compound in the data set. The Newly designed compounds were docked in the target receptor binding site (ID: 4LWU). The newly designed compound Pred 01 showed the highest affinity with a value of -9.4kcal / mol, while compound N°04 which represents the data set and control compound (Nutlin-3) showed binding energies of the order of -8.8 kcal / mol and -8.2kcal / mol, respectively. In addition, the roles of lipinski and veber were estimated, the results obtained demonstrate that the proposed molecules involve good oral bioavailability and an ability to diffuse through different biological barriers. For in-depth study, The Pred01 / receptor, N°04 / receptor and Nutlin-3 / receptor complexes were selected via dynamic simulation analyzes with a simulation time of 100 ns and, also their free binding energy was examined operating the MM-GBSA approach. The molecular docking results obtained accentuate the crucial residues responsible for the ligand / protein interaction, providing insight into the mode of interaction. The MD simulation analysis confirms the conformational stability of the selected complexes during the MD trajectory, and the fluctuations recorded are insignificant. The results of MM-GBSA reveal that the new compound Pred 01 exhibits the lowest free energy, which confirms the result of molecular docking.

This research aims to screen out the effective bioactive compounds from Coriander (Coriandrum sativum L.), which may be novel potential inhibitors of Eubacterium rectale for the prevention of colorectal cancer (CRC). A series of 8 coriander-derived chemical compounds previously assessed for their anti-inflammatory, antioxidant, and antidiabetic activities were tested against Carbohydrate ABC transporter substrate-binding protein and compared to the standard inhibitor Acarbose, to support their use as novel Eubacterium rectale inhibitors. Herein, these derivatives were submitted to a thorough analysis of docking studies, in which detailed interactions of the selected phytocompounds with carbohydrate ABC transporter substrate-binding protein were revealed. Molecular docking analysis recommends Rutin, Gallocatechin, and Epigallocatechin as the most potential Eubacterium rectale inhibitors among the eight selected phytochemical compounds. Subsequently, the stability of the three selected phytochemical complexes was checked using molecular dynamics (MD) simulation at 100 ns and Molecular Mechanics combined with Poisson-Boltzmann Surface Area (MM-PBSA). The results show quite good stability for Rutin and Gallocatechin. In silico ADMET prediction was performed on the selected compounds, and the findings revealed a reasonably good ADMET profile for both Rutin and Gallocatechin. The current findings predict that Gallocatechin could be a better CRC preventive natural compound, and, further in vitro, in vivo and clinical studies may confirm its therapeutic potential. Communicated by Ramaswamy H. Sarma

Cancer is one of the greatest challenges that worry the minds of scientists and threatens human life. Despite the presence of several drugs on the market, their effectiveness remains limited by its resistance. In this research, the Monte Carlo approach was used for QSAR modelling applying the representation of the molecular structure by the SMILES and optimal molecular descriptors. Correlation Ideality (IIC) and Correlation Contradiction Index (CCI)) were introduced as validation parameters to further estimate the predictive ability of the developed models. The statistical quality of the model developed with (IIC) was good compared to those without (IIC). The best QSAR model of the following statistical parameters: (R²train= 0.816, R²valid = 0.825) was selected to generate the activity-increasing and decreasing promoters studied, and these are the basis for the design of seven new candidates as an antiproliferative inhibitory agent. Additionally, the newly designed molecules, the most active compound in the dataset, erlotinib and melphalan as control compounds were docked in the EGFR receptor binding site. The docking results discovered that the proposed candidates had the highest potential and energy affinity. Besides, Lipinski’s Rule of Five, Synthetic Accessibility and ADME/Tox were performed to assess bioavailability and drug-likeness of proposed compounds. In addition, MD simulation accompanied by MM-PBSA analysis discovered that compound A1 and the screened compounds were stable and did not show significant fluctuations throughout the simulation time. Generally, this research showed that the selected model well explains the antiproliferative activity and also that the proposed compounds have high activity, good binding affinity and stable conformation with the reported target protein.

Tubulin plays an indispensable role in regulating various important cellular processes. Recently, it is known as a hopeful therapeutic target for the rapid division of cancer cells. Novel series of 2-oxoquinoline arylaminothiazole derivatives have been recently identified as promising tubulin inhibitors with potent cytotoxicity activity against HeLa cancer cell line. In this study, a 3D-QSAR approach by using CoMFA and CoMSIA techniques was applied to the reported derivatives to understand their pharmacological essentiality contributing to the tubulin inhibition activity and selectivity. The optimum CoMFA and CoMSIA models were found to have significant statistical reliability and high predictive ability after internal and external validation. By analyzing the contour maps, the electrostatic and hydrophobic interactions were found to be crucial for improving the inhibitory activity and four novel tubulin inhibitors (Compounds D1, D2, D3, and D4) were designed based on the validated 3D-QSAR models. Moreover, the docking findings showed that residues Gln136, Val238, Thr239, Asn167, Val 318 and Ala 316 played important roles for quinoline binding to tubulin. Among the newly designed compounds, compound D1 with the highest total scoring was subjected to detailed molecular dynamics (MD) simulation and compared to the most active compound. The conformational stability of compound D1 complexed with tubulin protein was confirmed by a 50-ns molecular dynamics simulation, which was congruent with molecular docking. Resumen. La tubulina juega un papel indispensable en la regulación de varios procesos celulares importantes. Recientemente, se le ha reconicodo como un agente promisorio para atacar la rápida división de las células cancerosas. Últimamente se ha identificado una nueva serie de derivados de arilaminotiazo-2-oxoquinolina como potenciales inhibidores de la tubulina, con una elevada actividad citotóxica contra la línea celular de cáncer HeLa. En este estudio, se aplicó a los derivados informados un estudio 3D-QSAR mediante el uso de técnicas CoMFA y CoMSIA para comprender los factores farmacológicos que contribuyen a la actividad como inhibidor y selectivo de la tubulina. Se encontró que los modelos CoMFA y CoMSIA óptimos tienen una confiabilidad estadística significativa y una alta capacidad predictiva después de la validación interna y externa. Al analizar los mapas de contorno, se descubrió que las interacciones electrostáticas e hidrófobas eran cruciales para mejorar la actividad inhibidora y se diseñaron cuatro nuevos inhibidores de la tubulina (compuestos D1, D2, D3 y D4) basados en los modelos 3D-QSAR validados. Además, los hallazgos de acoplamiento mostraron que los residuos Gln136, Val238, Thr239, Asn167, Val 318 y Ala 316 desempeñaron papeles importantes en la unión de la quinolina a la tubulina. Entre los compuestos de nuevo diseño, el compuesto D1 con la puntuación total más alta se sometió a una simulación detallada de dinámica molecular (MD) y se comparó con el compuesto más activo. La estabilidad conformacional del compuesto D1 unido a la proteína tubulina se confirmó mediante una simulación de dinámica molecular de 50 ns, que fue congruente con el acoplamiento molecular.

The investigation of dye-sensitized solar cells (DSSCs) based on different donor groups linked with cyanoacrylic acid electron acceptor by Selenophene as π-bridged (D-π-A) was performed based on density functional theory (DFT) time-dependent DFT (TDDFT). Different functional were tested W97XD, PBEPBE, CAM-B3LYP, and B3PW91, and compared with experimental results of the reference D1. The theoretical results with CAM-B3LYP functional at 6-311G (d,p) basis sets were capable of predicting the absorption maximum that has been reported experimentally. Calculations were made to establish the conformational orientation of the cyanoacrylic acid group and evaluate the effect of changing donor units' on the electronic properties of the ground state. Structural and electronic properties, along with the photovoltaic properties, were investigated. The LUMO and HOMO energy levels of these dyes can positively affect the process of electron injection and dye regeneration. Light-harvesting efficiency (LHE), injection driving force (ΔGinject), and total reorganization energy (total) were also discussed. To further support the previous proprieties, electronic excited state energies were obtained by TDDFT// CAM-B3LYP/6-311G(d,p) calculations. The calculated results of these dyes reveal that D8 dye possessing triphenylamine donor unit has the best electronic, optical properties, and photovoltaic parameters.

In the present work, a combined approach based on conceptual-DFT formalism and molecular docking simulations were performed to investigate the chemical reactivity of six Benzodiazepine analogs. Chemical reactivity descriptors derived from the conceptual DFT were determined and discussed to explain the global and local reactivity of the six studied analogs. Also, long-range interactions were studied using the quantitative analyses of molecular electrostatic potential (MEP) on van der Waals surface to identify the nucleophilic and electrophilic sites. Moreover, a statistical analysis was performed to assess the robustness of atomic charges to the basis set. The results revealed that Hirshfeld population analysis (HPA) was the most efficient for this purpose. Molecular docking simulations were performed to predict the binding affinities of the issued molecules and estimate the binding poses into four binding sites, three of them were recently discovered, located in GABAA receptor. DOI: http://dx.doi.org/10.17807/orbital.v13i4.1607

A cross-linked chitosan/(MnFe2O4) CCsMFO nanocomposite was prepared using co-precipitation methods and used as a nanomaterial to extract U(VI) and Th(IV) from an aqueous solution based on adsorption phenomena. The contact time of experiments shows a rapid extraction process within 30 min by the CCsMFO nanocomposite. The solution pH acts a critical role in determining qm value, where pH 3.0 was the best pH value to extract both ions. The pseudo-second-order equilibrium model illustrated the kinetics equilibrium modal extraction process. Adsorption isotherm of U(VI) at pH 3.0 by CCsMFO nanocomposite is an endothermic process. In contrast, the adsorption isotherm of Th(IV) at pH 3.0 by CCsMFO nanocomposite is an exothermic process. The reusability of CCsMFO nanocomposite was tested using basic eluents as suitable conditions for the chemical stability of CCsMFO nanocomposite; the reusability results show promising results for the removal of U(VI) adsorbed onto CCsMFO nanocomposite with 77.27%, after 12 h by Na2CO3 as eluent. At the same time, the reusability results show good reusability for removal of U(VI) adsorbed onto CCsMFO nanocomposite with 21.82%, after 8 h by EDTA as eluent.

International audience; This study aims to develop a new type of semiconductor materials. In this context, the coordination complex (CH 3-CH 2-C 6 H 4-NH 2) 2 ZnBr 2 material was subjected to UV-Vis spectroscopy and the dependent theoretical density functional theory (TD-DFT) studies. The optical properties such optical absorption, band gap and molecular orbital energies are determined and discussed. The experimental results and theoretical conclusions appear to be in good agreement. Although we checked that the experimental molecular geometry is predicted correctly using the (TD-DFT) method. The molecular electrostatic potential (MEP) was calculated to predict physicochemical properties. The molecular composition of HOMO-LUMO and their band gap energies are represented in order to explain the activity of the title compound. So, the studied material seems to have a semiconductor behavior.

Onze nouvelles molécules organiques de structure donneurs-espaceur-accepteurs (D-π-A) utilisées pour les cellules solaires organiques (OSC) basées sur la thiénopyrazine et le thiophène ont été étudiées par la théorie de la densité fonctionnelle (DFT) et la théorie de la densité fonctionnelle dépendante de temps DFT (TD-DFT), pour expliquer comment l’ordre de conjugaison influe sur les performances des cellules solaires. Le groupe accepteur d’électrons (ancrage) était composé de 2-cyanoacrylique pour tous les composés, tandis que l’unité donneuse d’électrons était variée et que son influence fut étudiée. Les résultats théoriques ont montré que les calculs TD-DFT, avec une fonction hybride d’échange – corrélation utilisant la méthode d’atténuation de Coulomb (CAM-B3LYP) en conjonction avec un modèle de solvatation à cycle continu polarisable (modèle de continuum polarisable, PCM) combinée avec la base 6-31G(d,p), était raisonnablement capable de prédire les énergies d’excitation, les spectres d’absorption et d’émission des molécules étudiées. Les niveaux d’énergie des orbitales moléculaires frontières (orbitale moléculaire occupée de plus haute énergie (HOMO) et orbitale moléculaire inoccupée de plus basse énergie (LUMO) de ces composés peuvent avoir un effet positif sur le processus d’injection et de régénération d’électrons. La tendance des lacunes calculées HOMO-LUMO se compare bien avec les données spectrales. En outre, les valeurs estimées de photovoltage en circuit ouvert (Voc) pour ces composés ont été présentées. L’étude des propriétés structurelles, électroniques et optiques de ces composés pourrait aider à concevoir des matériaux organiques photovoltaïques fonctionnels plus efficaces.

In this study, we have established two-dimensional quantitative structure propriety relationships (2D-QSPR) model, for a group of 78 molecules based on pyrazine, these molecules were subjected to a 2D-QSPR analyze for their odors thresholds propriety using stepwise Multiple Linear Regression (MLR). The 35 parameters are calculated for the 78 studied compounds using the Gaussian 09W, ChemOffice and ChemSketch softwares. Quantum chemical calculations are used to calculate electronic and quantum chemical descriptors, using the density functional theory (B3LYP/6-31G (d) DFT) methods.The model was used to predict the odors thresholds propriety of the test and training set compounds, and the statistical results exhibited high internal and external consistency as demonstrated by the validation methods.

The dielectric and electrical proprieties of Ethylcarbazole family based copolymer such as Poly(Ethylcarbazole-Terphenyl) (PEcbz-Ter), Poly(Ethylcarbazole-Anthracene) (PEcbz-Ant) and Poly(Ethylcarbazole-Furan) (PEcbz-Fur) were investigated over the frequency range from 1 kHz to 2 MHz. The dielectric constant ε'r for (PEcbz-Ter), (PEcbz-Ant) and (PEcbz-Fur) pellets was found to decrease as the frequency increases and it was recorded a value of 11  7 , 11  6 and 7  6 respectively at 1 kHz. The dielectric loss was investigated and have a value below 1% at 11 kHz, which is suitable for several energy storage applications.

In this work, a series of eight metal-free organic dyes based on triphenylamine as a donor and cyanoacetic acid as an acceptor of electrons with the donor-π-acceptor structure were studied by DFT and TD-DFT methods. Their electronic properties, absorption spectra, and molecular nonlinear optical (NLO) responses have been analyzed and reported. The influence of the change of π-conjugated linker on the electrochemical and photophysical properties of these metal-free organic dyes has been investigated and discussed in detail. The energy gap decreases by going from L1 to L8, which causes a large NLO response for the studied dyes. The natural bond orbital (NBO) analysis reveals that the separation of charge occurred upon photoexcitation and the electrons moved from the donor to the acceptor moiety. A high NLO response reveals that this kind of metal-free organic dyes has eye-catching and remarkably large first hyperpolarizability βtot values, especially for L7 ((E)-2-cyano-3-(3-((E)-2-(3-((E)-4-(diphenylamino)styryl)benzo[c]thiophen-1-yl)vinyl)benzo [c]thiophen-1-yl)acrylic acid) and L8 ((E)-2-cyano-3-(7-((E)-2-(7-((E)-4-(diphenylamino)styryl)thieno[3,4-b]pyrazin-5-yl)vinyl)thieno[3,4-b]pyrazin-5-yl)acrylic acid) with 150423.50 (a.u) and 202773.63 (a.u), respectively. Our research has been carried out to extend the conjugation of organic materials by controlling their π-conjugated linker to design new appealing NLO compounds. This study shows that these dyes are promising and have special properties for modern hi-tech applications such as solar cells, transistors, and organic light-emitting diodes (OLEDs), and even these properties can be adjusted and enhanced by the incorporation of the benzothiophene or thienopyrazine derivatives as a bridge so as to improve from L7 to L8.

The present work focuses on the design and development of new thienopyrazine-derivatives in alternate Donor-Acceptor (D-A) structure for solar cells applications. Eight molecules based on thienopyrazine combined with the electron-rich thiophene or bithiophene units have been investigated using the DFT and TDDFT methods with B3LYP functional implemented with 6-31G(d,p) basis set. The focus was on the effect of substitution and doping on the structural, optoelectronic, photovoltaic and transporting properties. The result shows that the substitution by bithiophene groups decreases energy gap (Eg), produces a high bathochromic shift and increases oscillator strength of the lowest-lying transition compared to the substitution with thiophene groups. The doping of studied molecules makes them more planar and improves their electronic properties. Other characteristics, such as the ionization potential (IP), electronic affinity (EA), reorganization energies (λ+ and λ−), voltage in open circuit (Voc), and charge transfer are discussed. All of the molecules show moderate values of voltage in open circuit and efficient charge transfer. In the light of these results, we suggest promising models of systems for applications in optoelectronic. OPVC solar cell based on the most appropriate designed molecule (low band gap and high VOC) in bulk heterojunction composite with [6,6] -phenyl-C61-butyric acid methyl ester (PCBM) as an acceptor has been modeled. A model energy band diagram is described for OPVC to simulate the energy transfer between active layers. These materials are potentially interesting for the realization of optoelectronic devices and can be qualified as future materials for renewable energy.

In this work, 11 newly designed organic dyes with D-π-A-A structure based on a 3D triphenylamine derivative known as indacenodithiophene-triphenylamine (IDTTPA) as a core, benzoic acid as the anchoring group and linked by various spacer fragments containing electron-acceptor character have been theoretically studied using density functional theory (DFT) and time-dependent DFT (TD-DFT) for dye-sensitized solar cells (DSSCs). This three-dimensional structure is very important in retarding dyes aggregation and charge recombination, besides enhancing the power conversion efficiency (PCE) of DSSC, we have further employed various auxiliary acceptors to facilitate the electron transfer from the donor to the acceptor. Seven different functionals containing 0–100% Hartree–Fock (HF) exchange and three solvent models have been tested in this study. Comparison between computational and experimental absorption of D1 indicates that the maximum wavelength was accurately reproduced by a BHandHLYP functional and solvation model based on density (SMD) solvent model. The molecular structures, energy levels, absorption spectra, light harvesting efficiency (LHE) and driving force of injection (ΔGinject) are calculated. To sum up, these results indicate that the addition of an auxiliary acceptor into the core of the dye molecule has a significant effect on several properties including the planarity showed in this investigation, the decreasing in gap energy of 1.15 eV, and a bathochromic shift of 180 nm. It was found that the dye D4 with auxiliary acceptor 1,2,5-thiadiazolo[3,4-d]pyridazine shows a strong tendency to planarization, and possess the lowest values for bandgap of and open-circuit photovoltage 1.544 eV and 0.733 eV, respectively, the highest $$ \Delta G^{\rm{inject}} $$ value (− 1.23 eV) and a maximum wavelength absorption of 608.85 nm, which makes this dye exhibits positive results and can be used as a promising candidate for DSSCs.

Because of the rapid increase in deaths due to Staphylococcus aureus (S. aureus) infection, significant resources have been invested over the past decade in new treatments. Successful therapy requires amalgam of therapies to delineate the pathogen while providing protection to the host cell. With this idea, indole-pyrimidine hybrids have been used to develop new antibacterial agents. This heterocyclic has a fundamental role in medicinal chemistry and serves as a key model for the development of various therapeutic agents including broad-spectrum antibacterial drugs. In this study, we have employed combined studies of Three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking which are validated by in silico ADME prediction; those methods have been performed on indole-pyrimidine hybrids against S. aureus. 3D-QSAR study was applied using Comparative Molecular Field Analysis (CoMFA) with Q2 of 0.560, R2 of 0.925, and Comparative Molecular Similarity Indices Analysis (CoMSIA) with Q2 of 0.577, R2 of 0.876. The predictive ability of these models was determined using a test set of molecules that gave acceptable predictive correlation (R2test) values 0.729 and 0.737 of CoMFA and CoMSIA respectively. Developed models and Docking methods provide guidance to design molecules with enhanced activity.

As continuation of our research work on the development and prediction of retention/release property of odorant molecules in Water and pectin gels, in this research, on the one hand, we investigate to establish the quantitative structure property relationship (QSPR) of the retention/release property of odorant molecules in dairy gels using principal components analysis (PCA) and multiple linear regression (MLR). We propose quantitative models according to these analyses. The multiple linear regression (MLR) method showed a correlation coefficient of 0.901 and 0.917 for DG (dairy gel without pectin) and DG-P (dairy gel with pectin) medias, respectively. On the other hand, we compared these results with the other of our previous works to detect the pectin impacts of the retention/release property of studied compounds in different medias (with and without pectin). The comparison indicates that the effects of pectin vary according molecules: adding pectin increases the retention of some molecules, but increases the release of other molecules.

In this work, we report on the structural, optical and electronic properties of a series of D-π-A-π-D type bis-dipolar Diphenylamino-Endcappedoligoarylfluorenes, (OF(2)Ar-NPh(2)). These molecules are studied by means of quantum chemical calculations based on density functional theory (DFT) using B3LYP functional with 6-31G(d,p) for all atoms and all states (ground and excited). The study of the geometrical parameters, ground state (p, n) showed that the structures of these molecules are planar. As a result, the electronic properties HOMOs, LUMOs, energy gaps, were determined from the fully optimized structures. The absorption of these molecules were calculated using (TD-DFT)-B3LYP/631G (d,p) method. This fundamental information is a valuable data in designing and making promising materials for optoelectronic applications.

In this work, we have studied conjugated polymers based on benzothiadiazole. the quantum chemical calculations on the structure and electronic and optics properties using the density functional theory (DFT), for the ground- and excited-state properties, respectively, using CAM-B3LYP and the 6-31G(d, p) basis set. These results will be devoted to the influence of the substitution benzothiadiazole on the electronic and optoelectronic properties of the polymer. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) levels of these compounds were calculated and compared to LUMO of fullerenes,C60 [6,6]-phenyl- C61-butyric-acid methyl ester to estimate the effectiveness of these molecules as electron donors in bulk heterojunction (BHJ) small molecules-fullerene solar cells. The absorption energies have been obtained from TD-DFT calculations performed on the excited-state optimized S geometries. Finally, the theoretical results suggest that both the introduction of benzothiadiazole groups contribute significantly to the electronic and optoelectronic properties of the alternating donor–acceptor–donor conjugated systems studied.

Herein, using the quantum methods DFT and TD-DFT, the optoelectronic properties and electronic structures of the eight compounds Ci (i = 1–8) based on bis[1]benzothieno[6,7-d:6′,7′-d′]benzo[1,2-b:4,5-b′]dithiophene (BBTBDT) with a D–π–D structure for Ci (i = 1–5) and D–π–A structure for Ci (i = 6–8) were investigated and discussed theoretically with the aim to apply these compounds as hole-transporting materials (HTM) in OLEDs. The electronic levels of the studied compounds calculated by B3LYP show that the proper energies of Ci (i = 6–8) match well for their efficient injection into a hole-injection layer (HIL). The compounds having the D–π–A structure appear more efficient than those having the D–π–D structure. The optoelectronic properties of the studied compounds obtained by TD-CAM-B3LYP elucidate that the C6, C7 and C8 compounds behave as electron-donating molecules and exhibit a charge transfer character in the UV-visible absorption and emission electronic spectra. Furthermore, the calculated reorganization energies, ionization potentials (IPs) and electron affinities (EAs) indicate that the extended C6, C7 and C8 compounds have highest charge-transporting ability among all compounds. It has been found that the D–π–A structure has more influence on the electronic and optoelectronic properties than the D–π–D structure. The hypothesized compound C7 has been found to be a good candidate for application in blue-emitting materials. Therefore, understanding these properties is important to design HTMs with exceptional properties such as stability and high efficiency.

In this paper, we present a theoretical analysis of the molecular structure of a conjugated molecule TTPA-TTF at the DFT level using the B3LYP method and the 6-31G (d) basis set. The TTPA-TTF mole-cule presented a twisted configuration, which gave it good solubility in different organic solvents. The Partial atomic charge, molecular electrostatic potential (MEP) map, and global reactivity descriptors highlight the reactive sites of the molecule with the possible prediction of its reactivity. Moreover, a clear image of the intra- and intermolecular interactions illustrates hyperconjugative interactions based on the charge delocalization that emerges from the natural bond orbital analysis. The non-linear optical proper-ties of the TTPA-TTF molecule can also be calculated by determining their first hyperpolarizabilities. The time-dependent density theory method TD-DFT-B3LYP 6-31G (d) was used for the study of absorption. The obtained results show a broad spectrum in the visible range favorable to harvest solar light.

Acetylcholinesterase (AChE) is a potential target for the development of small molecules as inhibitors for the therapy of Alzheimer’s disease (AD). To design highly active acetylcholinesterase inhibitors, a three-dimensional quantitative structure–activity relationship (3D-QSAR) approach was performed on a series of N-benzylpyrrolidine derivatives previously evaluated for acetylcholinesterase inhibitory activity. The developed two models, CoMFA and CoMSIA, were statistically validated, and good predictability was achieved for both models. The information generated from 3D-QSAR contour maps may provide a better understanding of the structural features required for acetylcholinesterase inhibition and help to design new potential anti-acetylcholinesterase molecules. Consequently, six novel acetylcholinesterase inhibitors were designed, among which compound A1 with the highest predicted activity was subjected to detailed molecular docking and compared to the most active compound. Extra-precision molecular dynamics (MD) simulation of 50 ns and binding free energy calculations using MM-GBSA were performed for the selected compounds to validate the stability. These results may afford important structural insights needed to identify novel acetylcholinesterase inhibitors and other promising strategies in drug discovery.

Coronavirus (COVID-19), an enveloped RNA virus, primarily affects human beings. It has been deemed by the World Health Organization (WHO) as a pandemic. For this reason, COVID-19 has become one of the most lethal viruses which the modern world has ever witnessed although some established pharmaceutical companies allege that they have come up with a remedy for COVID-19. To that end, a set of carboxamides sulfonamide derivatives has been under study using 3D-QSAR approach. CoMFA and CoMSIA are one of the most cardinal techniques used in molecular modeling to mold a worthwhile 3D-QSAR model. The expected predictability has been achieved using the CoMFA model (Q2 = 0.579; R2 = 0.989; R2test = 0.791) and the CoMSIA model (Q2 = 0.542; R2 = 0.975; R2test = 0.964). In a similar vein, the contour maps extracted from both CoMFA and CoMSIA models provide much useful information to determine the structural requirements impacting the activity; subsequently, these contour maps pave the way for proposing 8 compounds with important predicted activities. The molecular surflex-docking simulation has been adopted to scrutinize the interactions existing between potentially and used antimalarial molecule on a large scale, called Chloroquine (CQ) and the proposed carboxamides sulfonamide analogs with COVID-19 main protease (PDB: 6LU7). The outcomes of the molecular docking point out that the new molecule P1 has high stability in the active site of COVID-19 and an efficient binding affinity (total scoring) in relation with the Chloroquine. Last of all, the newly designed carboxamides sulfonamide molecules have been evaluated for their oral bioavailability and toxicity, the results point out that these scaffolds have cardinal ADMET properties and can be granted as reliable inhibitors against COVID-19., SARS-CoV-2, 3D-QSAR, carboxamides sulfonamide, Molecular docking, drug discovery, in silico ADMET.

The copolymer based on Poly(3, 4-Ethylene dioxythiophen) and Poly(n-Vinylcarbazole) was characterized by FTIR and Raman spectroscopy. The temperature and frequency evolutions of dielectric parameters are also plotted and studied. The dependence of ε” on the temperature shows relaxation process for studied copolymer especially with frequencies about 1kHz for the temperatures: 90°C < T < 118°C. The values of ε’∞, ε’’MAX, relaxation time and DC conductivity corresponding to the copolymer are also determined with the aim to provide dielectric analysis involving vital information about this new polymeric compound.

Cancer is one of the very common diseases requiring long-term treatment, tubulin plays an important role in the development of cancer, and the use of colchicine binding site inhibitors against Hepatocellular Carcinoma has become the most common approach. A series of thirty quinoline derivatives have recently been identified as promising tubulin inhibitors with potent activity against human Hepatocellular Carcinoma. To design anti-cancer drugs, we applied the 3D-QSAR approach, this method is based on two contours (CoMFA and CoMSIA), the results obtained in two these contours are (R2 = 0.98, Q2 = 0.68, r2ext = 0.96) and (R2= 0.98, Q2 = 0.57, r2ext = 0. 97), respectively, this indicates that the model is trustworthy. The results indicate that the hydrophobic field contributes more (58% ); based on these results, three quinoline derivatives (Z1, Z2, and Z3) are proposed as potent colchicine binding site inhibitors against hepatocellular carcinoma activities. Furthermore, molecular docking was utilized to compare the stability of complexes (ligand-receptor) based on the type of binding and the total score. The ADME has been utilized to evaluate the pharmacokinetic characteristics of the designed drugs; we can conclude that by using the results, all designed compounds are the best, and based on the results found at Docking and ADMET, and to identify the stability of newly compounds, molecular dynamic simulation was used for compounds Z2-3, the results found show that these molecules have better stability, which means that they have greater activity against hepatocellular carcinoma.