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Bioactive compounds are naturally occurring substances that have the ability to have physiological impacts on the human body. Due to their potential health advantages and their function in preventing and treating a variety of serious health risks, also this substances shown a high antibacterial and antibiofilm activities against bacteria that can affect health. Therefore, the purpose of the current investigation was to test different bioactive compounds (Thymol, Quercetin, Epicatechin gallate, Gallic acid, Coumarin, Caffeic acid, Tannic acid, Apigenin, Carvacrol, Carvone, Beta ionone and Eucalyptol), in order to see there effect against B. cereus. Additionally, the contact angle method was used to examine the influence of those substances on the physicochemical characteristics of PLA 3D printing material and there antiadhesive effect against bacteria studied. According to the antibacterial activities it should be noted that Carvacrol, Tannic acid and Epicatechin gallate were the most active against B. cereus bacteria. The measurements of the contact angle showed a substantial change in the physicochemical characteristics of 3D printing PLA, indicating an improvement in the electron donor character after treatment, and significantly changed the surface hydrophobicity following treatment from hydrophobe PLA to hydrophile PLA after treatement, we can also see that B. cereus can adhere to PLA before treatment but after treatment with bioactive compounds it has become unfavorable which means that our select compounds are indeed active. After the use of computational methods like ADMET analysis, molecular docking and dynamic analysis, it was practical to better understand the physicochemical and pharmacokinetic proprieties, drug-likeness, antibacterial antiadhesive properties of the studied phytocomponents.

This study presents the composition analysis of essential oils extracted from celery seeds (Apium graveolens L.) collected from Morocco. Essential oil of A. graveolens (AG-EO), were obtained through microwave-assisted hydro-distillation, and its composition was characterized using gas chromatography/mass spectrometry (GC/MS). antimicrobial properties were assessed utilizing disc diffusion and microdilution assay methods, while antioxidant activities were evaluated through spectrophotometric techniques. Additionally, in vivo anti-inflammatory effects were investigated. The molecular docking technique, a computational approach utilized to predict the binding of small molecules to specific proteins, was employed to elucidate the antioxidative and antibacterial characteristics of the constituent molecules. The physicochemical and pharmacokinetic features of absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) tests were anticipated to provide insights into the drug likeness, pharmacokinetic characteristics, and expected safety profiles upon ingestion and the potential pharmacological activity of the identified compounds. Fifteen constituent compounds representing 99.99% of AG-EO were identified and quantified by the use of GC/MS. The main constituent, comprising 64.58% of AG-EO was limonene. AG-EO demonstrated a significant DPPH free radical scavenging activity, showing estimated scavenging rates of 8.49±0.00 µg/mL, and 5.09±0.04 µg/mL for ABTS+. AG-EO exhibited reducing Power (RP) and total antioxidant activity (TAC) of 3.42±0.01 µg/mL and 245.93±0.04 mg AAE/mL, respectively. AG-EO exhibited significant antimicrobial activity against all tested microorganisms. Additionally, the anti-inflammatory activity demonstrated the remarkable efficacy of AG-EO. Taken together, the essential oil derived from celery seeds holds promise for large-scale utilization as an environmentally friendly preservative within the food and agriculture industries, effectively countering fungal growth and aflatoxin contamination in stored commodities. Additionally, it exhibits potential as a suitable candidate for the development of pharmaceutical drugs.

This exploratory study aims to identify the volatile compounds in PC-Eo (Petroselinum crispum L. essential oil) and evaluate its antioxidant and antimicrobial properties in vitro. Molecular docking, drug-likeness prediction, and pharmacokinetics (absorption, distribution, metabolism, excretion, and toxicity—ADMET) were among the in silico simulations that were used to explain the biological properties observed in vitro. For PC-Eo's chemical screening, gas chromatography-mass spectrophotometry (GC-MS) was employed. The antioxidant activity of PC-Eo was evaluated using five in vitro complementary techniques, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging activity, β-Carotene bleaching test (BCBT), reducing power (RP), and phosphomolybdenum assay (TAC). GC-MS analysis revealed that the primary components of PC-Eo are apiol (49.05 %), Myristicin (21.01 %), and 1-allyl-2,3,4,5-tetramethoxybenzene (13.14 %). The results of the in vitro antioxidant assays indicate that PC-Eo exhibits a superior antioxidant profile. The in vitro antimicrobial activity of PC-Eo was assessed against five strains, including 2 g-positive bacteria, 2 g-negative bacteria, and one fungal strain (Candida albicans). The disc-diffusion assay revealed significant antibacterial and antifungal activities against all strains, with zones of inhibition exceeding 15 mm. The microdilution test highlighted the lowest MIC and MBC values with gram-positive bacteria, ranging from 0.25 to 0.5 % v/v for MIC and 0.5–1.0 % v/v for MBC. For the fungal strain, MIC was recorded at 1.25 % and MFC at 2.5 % v/v. PC-Eo demonstrates bactericidal and fungicidal activity based on the MBC/MIC and MFC/MIC ratios. According to the ADMET study, the primary PC-Eo compounds have advantageous pharmacokinetic characteristics. These findings provide empirical support for the traditional uses of this plant and indicate its possible use as a natural remedy.

Life-threatening diseases like tuberculosis have raised concerns in the medical and scientific communities. The damage-causing disease makes the scientific community employ the in-silico approach for design of new inhibitors that can inhibit or retard the havoc caused by this deadly disease. The insilico approach was used in this study to create a mathematical model with promising molecular properties, and receptors from the library were used to screen compounds and estimate the kinetic ability of the screened inhibitors that can cure this disease. 2D molecular properties evolved in the built model with high predictive ability. Three inhibitors x, y, and z emerged with better and higher molecular properties, the lowest binding energy (and higher binding affinity), and a better pharmacokinetic assessment compared to the template used in designing the effective compounds, with binding affinities of -15.56 kcal/mol, -18.51 kcal/mol, and -18.58 kcal/mol, respectively. Virtual screening of these compounds showed that they have good binding energy and excellent docking positions with the inhibiting potential of the receptor. Also, pharmacokinetic predictions and ADMET, depict orally active ability of the inhibitors, possess good human intestinal absorption, and violate none of the RO5 as potential drug candidates to cure this disease. Hence, further laboratory tests are recommended for these to determine their toxicities and biological assays.

Tacrine was originally used as a palliative treatment for Alzheimer's disease (AD). But early applications soon revealed a number of its side effects on human health. That's why we decided to examine the effectiveness of novel tacrine derivatives known for their potent inhibition of GluN2B-NMDA receptors, to discover the leading candidates for treating AD in terms of safety and molecular stability towards NMDA receptors. As a result, CoMFA and CoMSIA models were generated using 3-dimensional quantitative structure-activity relationships (3D-QSARs) study, indicating that Electrostatic, Hydrophobic, and Steric fields have a vital function in the NMDAR-antagonizing activities. The predictive exactitude of the generated CoMFA model (Q2cv = 0.699, R2 training = 0.980, R2 test = 0.737) and the top model of CoMSIA (Q2cv = 0.646, R2 training = 0.867, R2 test = 0.761) has been successfully tested in both internal and external validations. The pharmacokinetics properties of in-silico ADME-Toxicity confirm the safety of C24 and C27 compounds, which were discovered to be free from any skin allergy toxicity and hepatotoxic effects, and would be able to passively break through the blood-brain barrier and ultimately penetrate the central nervous system with a very good level of absorption (HIA exceeding 95 %). The molecular docking results indicate that non-toxic inhibitors interact specifically with Gln110, Ser132, and Tyr109 amino acid residues as the main active sites of the transport protein encoded as 5EWJ.pdb. At last, the intermolecular mechanisms detected by the examined ligands labeled C24, and C27, revealed excellent levels of molecular stability towards the targeted protein along one hundred nano-seconds of molecular dynamics time.Therefore, C24 and C27 chemical compounds are strongly recommended to treat AD, due to their considerable similarity to drug candidates and high levels of molecular stability.

In recent years, there has been a focus on developing and discovering novel Bruton's tyrosine kinase (BTK) inhibitors, as they offer an effective treatment strategy for B-cell malignancies. BTK plays a crucial role in B cell receptor (BCR)-mediated activation and proliferation by regulating downstream factors such as the NF-κB and MAP kinase pathways. To address this challenge and propose potential therapeutic options for B-cell lymphomas, researchers conducted 2D-QSAR and ADMET studies on pyrrolopyrimidine derivatives that act as inhibitors of the BCR site in cytochrome b. These studies aim to improve and identify new compounds that could serve as more potent potential BTK inhibitors, which would lead to the identification of new drug candidates in this field.In our study, we used 2D-QSAR (multiple linear regression, multiple nonlinear regression, and artificial neural networks), molecular docking, molecular dynamics, and ADMET properties to investigate the potential of 35 pyrrolopyrimidine derivatives as BTK inhibitors. A molecular docking study and molecular dynamics simulations of molecule 13 over 10 ns revealed that it establishes multiple hydrogen bonds with several residues and exhibits frequent stability throughout the simulation period. Based on the results obtained by molecular modeling, we proposed six new compounds (Pred1, Pred2, Pred3, Pred4, Pred5, and Pred6) with highly significant predicted activity by MLR models. A study based on the in silico evaluation of the predicted ADMET properties of the new candidate molecules is strongly recommended to classify these molecules as promising candidates for new anticancer agents specifically designed to target Bruton's tyrosine kinase (BTK) inhibition.

In this study, a 2D-QSAR (quantitative structure–activity relationship) was performed on 54 new 2-Styrylquinoline derivatives as anticancer substances capable of inhibiting the p53 protein in the cell HCT116++. The 54 2-Styrylquinoline derivatives was calculated applying DFT 6-31G basis to calculate Quantum descriptors, using MM2 for: Topological, Physico-chemical, Geometrical and Constitutional. The study was carried out by performing multiple linear regression (R2 = 0.90), the QSAR model achieved was tested by artificial neural networks method, which is showed high predictability (R2ANN = 0.89). A DFT study was performed to determine the reactivity of the 2-Styrylquinoline derivatives using frontier molecular orbital analysis and analysis of the molecular electrostatic potential (MEP). Derivatives of 2–4 Styrylquinoline are studied for their synthetic accessibility and their similarity to drug. The obtained results show that all the evaluated compounds have similar properties to drug and are accessible to synthesize.A molecular docking analysis was performed for three compounds: 14, 34, and 54, having various reactivities against the p53 HCT116++ protein (identified by PDB ID: 2GEQ). The results showed strong interactions between the three ligands and the 2GEQ protein, the amino acids HIS 176, SER A180, PRO A188 and ARG A178 are the most active sites of the 2GEQ protein, and based on these result we performed a molecular dynamics simulation to evaluate the stability of our complexes. The MD demonstrates the thermodynamic stability of select compounds during 40 and 100 ns, with all three complexes showing a high level of structural stability.

The overexpression of cyclooxygenase-2 (COX-2) was clearly associated with carcinogenesis, and COX-2 as a possible target has long been exploited for cancer therapy. A group of 29 derivatives of 1, 5-diarylpyrazole was used to study its structural requirements using three-dimensional quantitative structure–activity relationship (3D-QSAR), the density functional theory method, molecular docking, and molecular dynamics. Four 3D-QSAR models were developed, and the predictive capability of the four selected models was also successfully tested using different validation methods. The contribution contours of the comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models effectively illustrate the relationships between the various chemical characteristics and their biological activities. Using the density functional theory method with the 6-31G (d, p) basis set and the Becke, 3-parameter, Lee-Yang-Parr (B3LYP) function to evaluate chemical reactivity properties, the results obtained from energy gaps of 3.431, 3.446, and 2.727 ev for molecules numbers 21, 22, and 23 indicate that these three molecules have good chemical stability and reactivity and select the most reactive regions in the three molecules studied. Molecular docking results revealed that the active sites of the COX-2 protein (PDB code: 3PGH) were residues ARG222, THR212, HIS386, HIS207, TYR148, and ASP382, in which the most active ligands and now ligands can inhibit the COX-2 enzyme. Based on the various results obtained by molecular modeling, four new compounds (N1, N2, N3, and N4) were proposed with significant predicted activity by different 3D-QSAR models. A molecular docking study and molecular dynamics simulations of the proposed new molecules (N1 and N2) and the most active molecule over 100 ns revealed that all three molecules establish multiple hydrogen interactions with several residues and also exhibit frequent stability throughout the simulation period. As a result, it is strongly recommended to consider the two newly proposed molecules, N1 and N4, as promising candidates for novel anti-cancer agents specifically designed to target COX-2 inhibition.

A systematic in-silico study based on molecular modeling techniques was conducted on thirty 3,4-disubstituted pyrrolidine sulfonamides derivatives to identify the drug candidate for treating schizophrenia and impairments associated with NMDA receptor hypofunction, through selective and competitive inhibition of GlyT1. QSAR analysis demonstrates that geometric and constitutional descriptors have a key function in human GlyT1 activity. The in-silico study concluded that the most active ligand labeled C19 was predicted to be a non-toxic inhibitor, with a desired ADME-Toxicity profile and a significant probability to penetrate the central nervous system (CNS). Molecular docking simulations confirmed that the C19 compound was docked to the active sites of drosophila melanogaster dopamine transporter (DAT) protein, creating a variety of chemical bonds towards TYR 124, ASP 475, GLU 480, ALA 479, and VAL 120 amino acids residues. The molecular dynamic (MD) technique combined with the MMGBSA approach confirmed that produced intermolecular interactions for the (DAT protein–C19 ligand) complex remain so stable during 100 ns of MD simulation time. Consequently, the C19 ligand is highly recommended for the treatment of schizophrenia and other disabilities linked to the hypofunction of glutaminergic NMDA receptors.

A structural class of forty glycine transporter type 1 (GlyT1) inhibitors, was examined using molecular modeling techniques. The quantitative structure-activity relationships (QSAR) technology confirmed that human GlyT1 activity is strongly and significantly affected by constitutional, geometrical, physicochemical and topological descriptors. ADME-Tox in-silico pharmacokinetics revealed that L28 and L30 ligands were predicted as non-toxic inhibitors with a good ADME profile and the highest probability to penetrate the central nervous system (CNS). Molecular docking results indicated that the predicted inhibitors block GlyT1, reacting specifically with Phe319, Phe325, Tyr123, Tyr 124, Arg52, Asp475, Ala117, Ala479, Ile116 and Ile483 amino acids of the dopamine transporter (DAT) membrane protein. These results were qualified and strengthened using molecular dynamics (MD) study, which affirmed that the established intermolecular interactions for (L28, L30–DAT protein) complexes remain perfectly stable along 50 ns of MD simulation time. Therefore, they could be strongly recommended as therapeutics in medicine to improve memory performance.