Design of novel potent selective survivin inhibitors using 2D-QSAR modeling, molecular docking, molecular dynamics, and ADMET properties of new MX-106 hydroxyquinoline scaffold derivatives.

Given the critical role of survivin (BIRC5) in tumor cell regulation, developing novel inhibitors represents a promising approach for cancer therapy. This study details the design of innovative survivin inhibitors based on the hydroxyquinoline scaffold of our previously reported lead compound, MX-106. Our study identified nine compounds whose inhibitory activity is expected to be superior to that of the most active molecule in the series. These compounds demonstrated potent suppression of MDA-MB-435 breast cancer cell proliferation in vitro and exhibited enhanced metabolic stability compared to the series' most active member. To evaluate these derivatives as potential survivin inhibitors, we employed a multi-faceted approach combining 2D-QSAR methods, molecular docking, molecular dynamics, and ADMET property assessment. Our molecular modeling studies led to the design of nine novel compounds (Pred1-Pred9) predicted to exhibit potent survivin inhibitory activity based on MLR models. To assess their suitability as drug candidates, we recommend a thorough evaluation of their ADMET properties. These compounds hold promise as innovative anticancer agents targeting survivin, similar to the established MX-106.

Coriandrum sativum L., essential oil as a promising source of bioactive compounds with GC/MS, antioxidant, antimicrobial activities: in vitro and in silico predictions.

Introduction: Coriandrum sativum L. essential oil (CS-EO) is being evaluated in vitro for its antioxidant and antimicrobial properties, and its volatile compounds are to be identified as part of this exploratory study. Methods: The processes underlying the in vitro biological properties were explained using in silico simulations, including drug-likeness prediction, molecular docking, and pharmacokinetics (absorption, distribution, metabolism, excretion, and toxicity-ADMET). Chemical screening of CS-EO was conducted using gas chromatography-mass spectrometry (GC-MS). Five in vitro complementary techniques were used to assess the antioxidant activity of CS-EO: reducing power (RP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging activity, ß-Carotene bleaching test (BCBT), and phosphomolybdenum assay (TAC). Results: According to GC-MS analysis, linalool (59.04%), γ-Terpinene (13.02%), and α-Pinene (6.83%) are the main constituents of CS-EO. Based on the in vitro antioxidant assay results, CS-EO has been found to have a superior antioxidant profile. Its estimated scavenging rates for ABTS+ are 0.51 ± 0.04 mg/mL, BCBT is 9.02 ± 0.01 mg/mL, and CS-EO is 1.52 ± 0.14 mg/mL. C. sativum demonstrated 6.13 ± 0.00 µg/mL for reducing power and 213.44 ± 0.45 mg AAE/mL for total antioxidant activity. The in vitro antimicrobial activity of CS-EO was assessed against five strains, including two gram-positive bacteria, two gram-negative bacteria, and one fungal strain (Candida albicans). Significant antibacterial and antifungal activities against all strains were found using the disc-diffusion assay, with zones of inhibition larger than 15 mm. The microdilution test highlighted the lowest MIC and MBC values with gram-positive bacteria, ranging from 0.0612 to 0.125% v/v for MIC and 0.125% v/v for MBC. The fungal strain's MFC was 1.0% v/v and its MIC was measured at 0.5%. Based on the MBC/MIC and MFC/MIC ratios, CS-EO exhibits bactericidal and fungicidal activity. The ADMET study indicates that the primary CS-EO compounds are good candidates for the development of pharmaceutical drugs due to their favorable pharmacokinetic properties. Conclusion: These results point to a potential application of this plant as a natural remedy and offer empirical backing for its traditional uses. It is a promising environmentally friendly preservative that can be used extensively in the food and agricultural industries to prevent aflatoxin contamination and fungal growth in stored goods.

In silico insights into the design of novel NR2B-selective NMDA receptor antagonists: QSAR modeling, ADME-toxicity predictions, molecular docking, and molecular dynamics investigations.

Based on a structural family of thirty-two NR2B-selective N-Methyl-D-Aspartate receptor (NMDAR) antagonists, two phenylpiperazine derivatives labeled C37 and C39 were conceived thanks to molecular modeling techniques, as novel NMDAR inhibitors exhibiting the highest analgesic activities (of pIC50 order) against neuropathic pain, with excellent ADME-toxicity profiles, and good levels of molecular stability towards the targeted protein of NMDA receptor. Initially, the quantitative structure-activity relationships (QSARs) models were developed using multiple linear regression (MLR), partial least square regression (PLSR), multiple non-linear regression (MNLR), and artificial neural network (ANN) techniques, revealing that analgesic activity was strongly correlated with dipole moment, octanol/water partition coefficient, Oxygen mass percentage, electronegativity, and energy of the lowest unoccupied molecular orbital, whose the correlation coefficients of generated models were: 0.860, 0.758, 0.885 and 0.977, respectively. The predictive capacity of each model was evaluated by an external validation with correlation coefficients of 0.703, 0.851, 0.778, and 0.981 respectively, followed by a cross-validation technique with the leave-one-out procedure (CVLOO) with Q2cv of 0.785, more than Y-randomization test, and applicability domain (AD), in addition to Fisher's and Student's statistical tests. Thereafter, ten novel molecules were designed based on MLR QSAR model, then predicted with their ADME-Toxicity profiles and subsequently examined for their similarity to the drug candidates. Finally, two of the most active compounds (C37 and C39) were chosen for molecular docking and molecular dynamics (MD) investigations during 100 ns of MD simulation time in complex with the targeted protein of NMDA receptor (5EWJ.pdb).

The effect of Dunaliella salina extracts on the adhesion of Pseudomonas aeruginosa to 3D printed polyethylene terephthalate and polylactic acid.

Polyethylene terephthalate (PET) and polylactic acid (PLA) are among the polymers used in the food industry. In this study, crude extracts of Dunaliella salina were used to treat the surface of 3D printed materials studied, aiming to provide them with an anti-adhesive property against Pseudomonas aeruginosa. The hydrophobicity of treated and untreated surfaces was characterized using the contact angle method. Furthermore, the adhesive behavior of P. aeruginosa toward the substrata surfaces was also studied theoretically and experimentally. The results showed that the untreated PLA was hydrophobic, while the untreated PET was hydrophilic. It was also found that the treated materials became hydrophilic and electron-donating. The total energy of adhesion revealed that P. aeruginosa adhesion was theoretically favorable on untreated materials, while it was unfavorable on treated ones. Moreover, the experimental data proved that the adhesion to untreated substrata was obtained, while there was complete inhibition of adhesion to treated surfaces.

Plant-derived bioactive compounds for the inhibition of biofilm formation: a comprehensive review.

Biofilm formation is a widespread phenomenon that impacts different fields, including the food industry, agriculture, health care and the environment. Accordingly, there is a serious need for new methods of managing the problem of biofilm formation. Natural products have historically been a rich source of varied compounds with a wide variety of biological functions, including antibiofilm agents. In this review, we critically highlight and discuss the recent progress in understanding the antibiofilm effects of several bioactive compounds isolated from different plants, and in elucidating the underlying mechanisms of action and the factors influencing their adhesion. The literature shows that bioactive compounds have promising antibiofilm potential against both Gram-negative and Gram-positive bacterial and fungal strains, via several mechanisms of action, such as suppressing the formation of the polymer matrix, limiting O2 consumption, inhibiting microbial DNA replication, decreasing hydrophobicity of cell surfaces and blocking the quorum sensing network. This antibiofilm activity is influenced by several environmental factors, such as nutritional cues, pH values, O2 availability and temperature. This review demonstrates that several bioactive compounds could mitigate the problem of biofilm production. However, toxicological assessment and pharmacokinetic investigations of these molecules are strongly required to validate their safety.

Petroselinum crispum L., essential oil as promising source of bioactive compounds, antioxidant, antimicrobial activities: In vitro and in silico predictions.

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, ß-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.

The Anti-urolithiatic effect of the roots of Saussurea costus (falc) Lipsch agonist ethylene glycol and magnesium oxide induced urolithiasis in rats.

Phytotherapy, which involves the use of plant extracts and natural compounds for medicinal purposes, is indeed a promising alternative for managing urinary lithiasis. Many plants have been studied for their potential to prevent and treat kidney stones, and they may offer a more natural and potentially less harmful approach compared to conventional treatments. Additionally, phytotherapy may be more cost-effective. The aim of the present study was to investigate the antilithic potential of extracts and essential oils of Saussurea costus (Falc) Lipsch in two in vivo models, one on ethylene glycol-induced calcium oxalate crystal formation and the other to assess the effects of these extracts on magnesium oxide-induced struvite crystal formation. The experiment involved the administration of different doses of aqueous and ethanolic extracts of S. costus (200 and 400 mg/kg) and essential oils (25 and 50 mg/kg) to male Wistar rats, followed by the evaluation of various physiological, biochemical and histopathological parameters. The results demonstrated that the administration of S. costus essential oils and extracts had significant effects on the rats, influencing body weight, urine volume, crystal deposition, cytobacteriological examination of urine, and serum biochemical parameters. Histopathological examinations revealed varying impacts on the kidneys and livers of the treated rats. The findings suggest that S. costus extracts and essential oils may hold promise in inhibiting calcium oxalate crystal formation in vivo and influencing various physiological and biochemical parameters in rats. Overall, the 200 mg/kg ethanolic extract of S. costus demonstrated antilithiatic efficacy, did not exhibit signs of toxicity and reduced the number of crystals in the kidneys. Furthermore, the study did not find a significant effect on reducing struvite crystals.