Molecular Docking Studies Research Articles

Study of Molecular Docking, Molecular Dynamics, Pharmacokinetics and Toxicity Prediction: Compounds from Nigella sativa Linn, Andrographis paniculata Nees, and Propolis as Inhibitors of Mycobacterium tuberculosis Growth

Background: Tuberculosis (TB) is caused by *Mycobacterium tuberculosis*, and Multiple Drug-Resistant Tuberculosis (MDR-TB) arises from resistance to first-line treatments like Rifampicin and Isoniazid. Since current TB medications have been used for over four decades, discovering new drug candidates is critical. This research focuses on herbal compounds—Black cumin (*Nigella sativa*), Sambiloto (*Andrographis paniculata*), and propolis—as potential inhibitors of *M. tuberculosis* by targeting DHFR. The objective of the study is to predict the activity of these herbal compounds prior to in vitro and in vivo testing. Methods: This study employed computational tools, including Molegro Virtual Docking (MVD) and Molecular Dynamics (MD), to assess the interactions of the herbal compounds with DHFR (PDB ID: 2CIG). Pharmacokinetic predictions were also conducted to evaluate the absorption and toxicity of the compounds. Results: Molecular docking and MD simulations indicated that Andrographolide, Thymoquinone, and Caffeic Acid Phenethyl Ester effectively inhibited the growth of *M. tuberculosis*. The analysis revealed favorable binding interactions and conformational changes in DHFR, with significant activity observed for Thymoquinone. Conclusion: This study suggests that Andrographolide, Thymoquinone, and Caffeic Acid Phenethyl Ester may serve as promising candidates for further development as anti-tuberculosis drugs. Subsequent in vitro and in vivo studies are warranted to validate their therapeutic potential.

Molecular Docking to Predict a Novel Bioactive Compound as an Inhibitor of Beta Catenin in Oral Squamous Cell Carcinoma

Background: Efforts aimed at enhancing patient survival have focused on early detection and diagnosis, followed by prompt treatment of potentially malignant disorders, aiming to halt their advancement into oral cancer. Recent research has shed light on the pivotal role of the Wnt/B-catenin signaling pathway in the pathogenesis of potentially malignant oral conditions. This pathway undergoes a progressive activation process across various degrees of epithelial dysplasia, including mild, moderate, and severe dysplasia. Beta-catenin (B-catenin) triggers the activation of genes associated with crucial cellular processes, which include cell growth, viability, differentiation, and migration. Aims: In the present study, we aimed to design a novel drug with 3 bioactive compounds through insilico analysis, assess its efficacy against B-catenin, and develop a new pharmacophore with an emphasis on B-catenin inhibition. Materials and Methods: Based on prior literature, three molecules possessing potent beta-cateninblocking properties were selected, namely rosmarinic acid, zosterin, and stigmasterol. To evaluate their binding affinities, molecular docking studies were conducted using the Lamarckian Genetic Algorithm implemented in AutoDock Tools 1.5.7. Initially, AutoGrid was employed to construct a grid box for docking purposes. The estimated binding poses of each compound were subjected to clustering analysis. The interactions between the compounds and beta-catenin were visualized and explored using PyMOL software. Results: Stigmasterol displayed the most substantial binding energy with a value of -3.86 kcal/mol, followed by rosmarinic acid and zosterin. Conclusion: Bioactive components can be used for beta-catenin pathway blocking. Future research should be carried out to assess these substances in more clinically relevant cancer models.

7-(Substituted amino)-5-methylthioazolo[1,5-a]pyrimidines: Synthesis, cytotoxic properties in vitro and molecular docking

A method for the synthesis of new 7-(substituted amino)-5-methylthioazolo[1,5-a]pyrimidines has been developed. Based on the MTT test, IC50 values were calculated for the obtained compounds against lung carcinoma (A549), liver carcinoma (HepG2), embryonal rhabdomyosarcoma (Rd) and human embryonic kidney (HEK 293) cell lines. Some compounds from the series demonstrated activity close to the reference drug, but with a certain selectivity. Based on the results of MTT assay and molecular docking studies for the catalytic subunits of PI3K, two isoforms (PI3Kβ and PI3Kδ) were assumed as the targets for the new series of azolo[1,5-a]pyrimidines with cytotoxic effect on the rhabdomyosarcoma cell line.

Targeting Human Papillomavirus 33 E2 DNA Binding Domain With Polyphenols: Unveiling Interactions Through Biophysical and In Silico Methods.

The human papillomavirus (HPV) 33 is a high-risk strain that causes lesions with potential cancerous outcomes. Its E2 protein regulates the viral protein transcription and life cycle maintenance. The DNA binding domain (DBD) of the E2 protein plays a crucial role in the viral life cycle. The DBD region of the E2 protein is particularly interesting for targeting and finding potential inhibitors to inhibit its function or dimerization. Given the limited research on HPV 33 and its proteins, the present work delved into the interaction of two natural polyphenolic compounds, resveratrol, and baicalein, with the E2 DBD of HPV 33 using biophysical and in silico studies. Fluorescence studies of the E2 DBD-polyphenol complexes showed fluorescence quenching with a binding constant of the order of 106 M-1. Circular dichroism data reveal conformational changes upon binding with the polyphenols, possibly due to distinct binding sites of the E2 DBD. Differential scanning calorimetry exhibited higher melting temperatures for the two complexes than alone DBD, suggesting the complexes' stability. ITC experiment suggested favorable binding reactions with kd values in the micromolar range. Molecular docking and dynamic simulation studies revealed that the resveratrol binds to the helical region and baicalein near the central dimeric interface of E2 DBD with a good binding affinity, forming a stable protein-ligand complex during the run of 100 ns simulation. Therefore, the current study identifies both polyphenolic compounds as promising candidates for potential antiviral drug development.

Design, Synthesis, and Biological Evaluation of Novel Heterocyclic Derivatives of 2,4‐Thiazolidine Dione as Anti‐Cancer Agents

ABSTRACTThis study explores the development of novel 2,4‐thiazolidinedione derivatives as potential anticancer agents. We report the synthesis of 15 novel analogs utilizing a strategic approach focused on intermediate diversification. Key intermediates, (Z)‐5‐([1,1′‐biphenyl]‐4‐ylmethylene)thiazolidine‐2,4‐dione 5a and (Z)‐5‐(benzo[1,3]dioxol‐5‐ylmethylene)thiazolidine‐2,4‐dione 5b, were synthesized via Knoevenagel condensation and acetal formation reactions, respectively. Subsequent N‐alkylation reactions provided a platform for introducing diverse functionalities and exploring structure–activity relationships to optimize the medicinal chemistry profile of these novel compounds. The synthesized compounds were tested against various human cancer cell lines, including for breast (MCF‐7, MDA‐MB‐453), lung (A549), and prostate (PC‐3) cancers, using an MTT assay. Compounds 8c and 10g emerged as particularly promising, exhibiting activity against all tested cell lines with IC50 values between 3.41 ± 0.51 and 40 μM. These compounds also induced apoptosis, suggesting that they inhibit cell proliferation through this cell death pathway. Moreover, relative molecular docking studies provided evidence that compound 8c likely functions by intercalating with DNA.

Potent α-glucosidase inhibitors with benzimidazole-propionitrile hybridization; synthesis, bioassay and docking study.

Background: Diabetes is characterized by a lack of insulin and insensitivity to insulin. In 2013, the global diabetes population was 382million, with 90% of them having type 2 diabetes (non-insulin-dependent). It is predicted that this number will increase to 592million by 2035.Aim: Here, we aimed to synthesize a series of benzimidazole-based derivatives B1-B32 with α-glucosidase inhibition potential as antidiabetic agents.Methods: Compounds B1-B32 were prepared in three three-step reactions, and the structures were elucidated using spectroscopic methods, namely 1H NMR, 13C NMR, MS and IR. Enzyme inhibition and kinetic study were done using commercial assay kits, and molecular docking study using autodock4.Results: Bioassay data showed that twenty-four out of the thirty-two tested compounds exhibited IC50 values ranging from 44 to 745μM, surpassing the standard molecule, acarbose (IC50: 750μM). it was determined that the best compound, B10, functions as a competitive inhibitor. Additionally, a molecular docking study provided insights into the interactions between the four most promising compounds (B5, B6, B10 and B28) and the active site residues within the enzyme.Conclusion: The tested compounds are interesting α-glucosidase inhibitors, which indicates the benefit of more bioassay studies, especially in vivo studies.

Design, synthesis, and mechanism study of novel tetrahydroisoquinoline derivatives as antifungal agents.

In screening for natural-derived fungicides, a series of 32 novel tetrahydroisoquinoline derivatives were designed and synthesized based on tetrahydroisoquinoline alkaloids. Their structures were verified by 1H NMR, 13C NMR, HRMS, and single X-ray crystal diffraction analysis. Most of the target products exhibited medium to excellent antifungal activity against 6 phytopathogenic fungi in vitro at a concentration of 50mg/L. Interestingly, compounds A13 and A25 with EC50 values of 2.375 and 2.251mg/L against A. alternate were similar to boscalid (EC50 = 1.195mg/L). The in vivo experiments revealed that A13 presented 51.61 and 70.97% protection activities against A. alternate at the dosage of 50 and 100mg/L, respectively, which were equal to that of boscalid (64.52 and 77.42%). SDH enzyme assays and molecular docking studies indicated that compound A13 may act on SDH. In addition, the SEM analysis showed that compound A13 could strongly damage the mycelium morphology. These results revealed that A13 may be a promising lead compound for the development of natural-derived fungicides.

Evaluation of antiviral efficacy of graphene oxide nanosheets on dengue virus-infected Vero cells: in-vitro and in-silico approaches

Emerging viral diseases have led to an increased demand for novel therapeutic medicines. Graphene nanostructures exhibit excellent inhibitory antiviral effects owing to their unique physic-chemical properties. In this study we have investigated the potential of graphene oxide (GO) nanostructures for antiviral activity. GO was synthesized by Modified Hummer’s method and fully characterized using several chemical-physical techniques to confirm the structure, morphology, optical properties, chemical composition and oxidation states. The antiviral property of the GO was investigated against serotype-2 dengue virus. The results suggest that the antiviral action is attributed to the negative charge of the graphene sheets due to the presence of oxygenated functional groups. Dengue virus −2 infection was suppressed by 90% with GO in a dose-dependent manner. Cytotoxic features of GO against Vero cells were observed when treated at higher concentrations (>75 μg ml−1 IC 50 concentration). The in-silico investigation showed that the interaction between GO nanosheets and serotype-2 dengue virus occurred within the ligand-protein complex as confirmed by molecular docking studies. These results emphasize that GO has strong antiviral activity against serotype-2 dengue virus.

Novel Antioxidant Peptides from Fermented Whey Protein by Lactobacillus rhamnosus B2-1: Separation and Identification by in Vitro and in Silico Approaches.

Whey is a byproduct of the dairy industry and is rich in protein. To enhance the significance of such byproducts and find efficacious antioxidants for combating oxidative stress, this study reported on the preparation, purification, and identification of novel peptides with antioxidant activities from whey protein metabolites following fermentation by Lactobacillus rhamnosus B2-1. The isolation and identification processes involved macroporous adsorption resin column chromatography, gel filtration column chromatography, and liquid chromatography-tandem mass spectrometry. Therein, three novel antioxidant peptides (PKYPVEPF, LEASPEVI, and YPFPGPIHNS) were selected to be synthesized, and they demonstrated remarkable antioxidant activities in vitro chemical assays. PKYPVEPF, LEASPEVI, and YPFPGPIHNS (100 μg/mL) displayed a notable cytoprotective impact on HepG2 cells under oxidative stress induced by H2O2, increasing the cell viability from 49.02 ± 3.05% to 88.59 ± 10.49%, 82.38 ± 19.16%, and 85.15 ± 7.19%, respectively. Moreover, the peptides boosted the activities of catalase and superoxide dismutase in damaged cells and reduced reactive oxygen species levels. The molecular docking studies highlighted that these antioxidant peptides efficiently bound to key amino acids in the Kelch domain of Keap1, thereby preventing the interaction between Keap1 and Nrf2. In conclusion, PKYPVEPF, LEASPEVI, and YPFPGPIHNS demonstrated substantial antioxidant activity, suggesting their potential for widespread application as functional food additives and ingredients.

Molecular Insights into the Potential Anticancer Property of a Diimine-Diazo Molecule: A Molecular Docking and Molecular Dynamics Simulations Perspective

Cancer is a disease in which cells grow abnormally and uncontrollably and destroy body tissue, and it is one of the most important threats to human health. In this study, the interaction of a molecule containing imine and azo groups (DIDA) with tumor growth-related VEGFR2 (PDB ID: 2XIR) and EGFR (PDB ID: 1M17) proteins was investigated by molecular docking and molecular dynamics simulation methods. The molecular docking study revealed that the best binding occurred between DIDA-2XIR with a binding energy of -12.4 kcal/mol. Molecular dynamics simulation was used to verify the stability of the DIDA-2XIR complex. RMSD, RMSF, SASA, Rg parameters and number of hydrogen bonds obtained during molecular dynamics simulations showed that the DIDA-2XIR complex was stable at the molecular level. Our findings have made an important contribution to the understanding of the mechanism of interaction of the DIDA with VEGFR2 and support its availability as a potential VEGFR2 inhibitor.

Empagliflozin ameliorates olfactory bulbectomy-induced depression by mitigating oxidative stress and possible involvement of brain derived neurotrophic factor in diabetic rats

Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has recently reported to prevent the depression as chronic animal model. However, its impact on neuroinflammation-mediated depression were remains unexplored. The present study aimed to explore the antidepressant potential of empagliflozin using a neuroinflammation-mediated depression involving the olfactory bulbectomy (OBX) model in rats. To establish this model, initially a low dose of streptozotocin was injected to induce diabetes in all group of animals. Following the confirmation of hyperglycemia, OBX surgery was performed. Post-surgery, the drug treatments were administered orally for 14 consecutive days. The study evaluated the effects of daily oral administration of empagliflozin at doses of 5 and 10 mg/kg, alongside metformin (200 mg/kg) and clomipramine (50 mg/kg), on OBX-induced behavioral depression in rats. Separate sham and vehicle control groups were also maintained. Behavioral parameters in open field, forced swim test, elevated plus maze and splash test were recorded on 28th day. Results showed that empagliflozin, particularly at the higher at the higher dose, significantly enhanced behavioral outcomes, evidenced by increased distance traveled, greater open arm entries, and reduced immobility, alongside a notable reduction in grooming time. Moreover, empagliflozin significantly restored the antioxidants level specifically Glutathione (GSH) and Catalase (CAT) in OBX insulted rat brain and reversed Lipid peroxidase (LPO). Notably, molecular docking study demonstrated a good binding affinity of empagliflozin for Brain-Derived Neurotrophic Factor (BDNF), suggesting that its antidepressant effects may be mediated through the modulation of the BDNF pathway. These findings support the potential therapeutic application of empagliflozin for depression, particularly in cases associated with neuroinflammation and oxidative stress.

Antifungal Efficacy of Ultrashort β-Peptides against Candida Species: Mechanistic Understanding and Therapeutic Implications.

Candidiasis, a condition spurred by the unchecked proliferation of Candida species, poses a formidable global health threat, particularly in immunocompromised individuals. The emergence of drug-resistant strains complicates management strategies, necessitating novel therapeutic avenues. Antimicrobial peptides (AMPs) have garnered attention for their potent antifungal properties and broad-spectrum activity against Candida species. This study assessed the antifungal effectiveness of ultrashort β-peptides against Candida strains, with a specific focus on peptide P3 (LAU-β3,3-Pip-β2,2-Ac6c-PEA). Our findings showed P3's remarkable fungistatic and fungicidal activities against Candida albicans, exhibiting an MIC of 4 μg/mL, comparable to those of standard antifungal drugs. The MIC value remained unchanged in the presence of ADC and BSA, indicating that serum albumin does not diminish the activity of P3. P3 demonstrates synergistic effects when combined with Fluconazole (FLU), Itraconazole (ITR), and Nystatin (NYS) to the extent that it becomes effective at 0.125, 0.125, and 0.03125 μg/mL, respectively. Concentration versus time-kill kinetics showed its time-dependent activity up to the first 12 h against C. albicans, and later concentration also played a role; indeed, at 24 h the whole culture was sterilized at 8× MIC. Post-antifungal effect assays confirmed prolonged suppression of pathogen growth after the removal of P3 from the media for significant durations. More importantly, P3 inhibits hyphae formation and biofilm development of Candida, outperforming Fluconazole with respect to these properties. Mechanistic insights display P3's potential to disrupt fungal cell membrane integrity and dose-dependent inhibition of ergosterol biosynthesis, essential for fungal cell wall integrity. Using the Bradford assay, it was observed that extracellular protein concentrations increased with higher doses of the compound, thereby validating the effect of P3 on membrane integrity. A comparative gene analysis using RT-PCR showed that P3 downregulates ERG3, ERG11, and HWP1, which are crucial for the survival and pathogenicity of C. albicans. The impact of P3 on ERG11 and ERG3 is more effective than that of Fluconazole. Molecular docking studies revealed strong binding of P3 to various isoforms of lanosterol 14-α-demethylase, a key enzyme in ergosterol synthesis. Furthermore, molecular dynamic simulations validated the stability of the most promising docking complex. Overall, our findings underscore P3's potential as a leading candidate for the development of innovative antifungal therapies, warranting further investigation and optimization.

Synthesis, α-Glucosidase, α-Amylase, and Aldol Reductase Inhibitory Activity with Molecular Docking Study of Novel Imidazo[1,2-a]pyridine Derivatives.

Inhibition ofaldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) are some of the essential targets in diabetes mellitus (DM). Here, a series of imidazo[1,2-a]pyridine-based 1,3,4-thiadiazole derivatives (8a-k) were successfully synthesized and characterized using 1H NMR, 13C NMR, and HRMS spectroscopic techniques. The inhibition effects of the synthesized derivatives against AR, α-GLY, and α-AMY were evaluated using both in vitro and in silico methods. In vitro studies revealed that the derivatives (8a-k) showed significant inhibition activity. The results showed that the novel derivatives (8a-k) demonstrated potential inhibitory activity, with K I values covering the following ranges: 23.47 ± 2.40 to 139.60 ± 13.33 nM for AR and 6.09 ± 0.37 to 119.80 ± 12.31 μM for α-GLY, with IC50 values 81.14 to 153.51 μM for α-AMY. Furthermore, many of these compounds exhibited high inhibition activity, while some of them showed higher potency than the reference compounds. Molecular docking of the target compounds was carried out in the active sites of AR (PDB ID: 4JIR) and α-GLY (PDB ID: 5NN8).

Appraisal of chemical composition and biological activities of thyme essential oil: an insight to in-silico molecular docking studies

The current study aims to ascertain the chemical composition and biological activities of thyme leaves essential oil (TEO), with an emphasis on its in silico molecular docking studies targeting the antibacterial properties of its constituents. TEO was extracted from dried leaves using a standardized procedure, with a yield of 0.75%. The chemical constituents of TEO were identified using Gas Chromatography-Mass Spectrometry (GC-MS). The primary compounds detected included carvacrol, o-acetyl thymol, α-pinene, and spathulenol. Subsequently, the antioxidant activity of the isolated oil was measured, and the results showed that the total phenolic contents (TPC) was 4.69 ± 0.17 GAE mg/100 g, the total flavonoid contents (TFC) was 1.45 ± 0.04 CE mg/100 g, the ferric reducing antioxidant potential (FRAP) ranged from 0.07-0.81, and the DPPH radical scavenging activity was 42.88-86.94%. TEO exhibited notable antibacterial activity against certain strains of Staphylococcus aureus and Escherichia coli. The molecular docking studies were then conducted to further investigate the interaction of TEO’s potent metabolites with key bacterial enzymes, identifying spathulenol and caryophyllene as the best-interacting ligands. Hemolytic activity tests of TEO indicated negligible cytotoxic effects. These findings support that TEO holds great potential for the development of functional food and nutra-pharmaceuticals.

Wedelolactone alleviates inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway in osteoarthritis

Inflammation and extracellular matrix (ECM) degradation are two major factors involved in the pathogenesis of osteoarthritis (OA). Wedelolactone, a natural compound classified as a coumestan, is isolated from the medicinal plants Eclipta alba and Wedelia calendulacea. In this study, we assessed the protective effects of Wedelolactone on chondrocytes in OA. Our findings show that pretreatment with Wedelolactone effectively inhibited the IL-1β-induced upregulation of COX‑2, iNOS, TNF-α, and IL6 in chondrocytes, contributing to inflammation suppression. Moreover, pretreatment with Wedelolactone followed by IL-1β treatment significantly increased the expression of Collagen II and SOX9, while decreasing the expression of Adamts5, MMP1, MMP3, and MMP13, thereby promoting ECM protection. Through Network pharmacology Analysis, we identified 14 key targets that link Wedelolactone and OA. GO and KEGG pathway analysis suggested that Wedelolactone primarily impacted OA by targeting inflammatory responses, particularly the NF-κB signaling pathway. Further studies demonstrated Wedelolactone prevented IL-1β-induced activation of NF-κB signaling pathway by inhibiting the translocation of p65 and the preventing the degradation of IκBα in human chondrocytes. Molecular docking studies also indicated that Wedelolactone can directly bind to the NF-κB complex, thereby inhibited the nuclear localization of p65. In vivo experiments demonstrated that Wedelolactone can alleviate cartilage damage in DMM mice model. In summary, Wedelolactone appears to mitigate inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway, thereby alleviating OA progression. Our results suggested Wedelolactone may offer therapeutic advantages for OA treatment.

Engineering Neuroglobin for Synthesis of Chiral Organoborons via Carbene B-H Insertion.

Organoborons have recently received much attention, while a biocatalytic platform for the synthesis of chiral organoborons is limited only to Rma cytochrome c. In this study, we exploited the other heme protein, neuroglobin (Ngb), and engineered a quadruple mutant, A15C/H64G/V68F/F28M Ngb, by redesigning the heme active site using the structural information on A15C Ngb and molecular docking studies. The enzyme was shown to be efficient in catalyzing carbene transfer B-H insertion reactions between pyridine/quinoline boranes and benzyl 2-diazopropanoates and their derivatives (29 examples). The designed cavity in the heme distal site favors the binding of large volume substrates such as those containing a quinoline, naphthyl, or biphenyl group. As further determined by the X-ray crystallography of 6c, the chiral products are in the R-configuration, with up to 98:2 e.r. Furthermore, both the whole cell and cell lysate containing the enzyme are reactive toward the B-H insertion reactions. This study presents a convenient biocatalytic platform that may be generally applicable for the synthesis of functional chiral organoborons.

Benzimidazolium salts bearing ester group: Synthesis, characterization, crystal structure, molecular docking studies, and inhibitory properties against metabolic enzymes

In this work, the synthesis of several unsymmetrical benzimidazolium salts with an ester (2-ethoxy-2-oxoethyl) group on the nitrogen atom is described. The structures of all compounds were fully characterized by spectroscopic (1H, 13C NMR, FTIR) and analytical (elemental analysis) methods. However, single-crystal X-ray diffraction analysis elucidated the molecular and crystal structures of compounds 1a and 1c. Asymmetric units of both crystal structures contain two crystallographically independent molecules and two bromide anions. All compounds exhibited substantial inhibition against the cytosolic carbonic anhydrase isoforms (hCA I and hCA II) and acetylcholinesterase (AChE) with Ki values 51.00–45.18 nM, 46.94–305.65 nM, and 17.57–65.68 nM, respectively. Notably, compound 1d showed extreme inhibitory effect against hCA I with 51.00±5.31 nM (AZA: 275.44±13.32 nM), hCA II with 46.94±5.44 nM (AZA: 236.55±17.88 nM) and AChE with 17.57±3.14 nM (TAC: 80.44±6.88 nM). In silico approach showed that compound 1d could form stable complexes with target enzymes with a different binding affinity (BE:9.01 kcal/mol for AChE; -7.22 kcal/mol for hCA II and -6.51 kcal/mol for hCA I). The results supported the medical potential of benzimidazolium salts containing ester group. They significantly lighted our knowledge about the chemistry of side groups on phenyl ring especially in the para position as compared to ortho and meta positions.

Postharvest integration of prickly pear betalain-enriched gummies with different sugar substitutes for decoding diabetes type-II and skin resilience - in vitro and in silico study

Postharvest processing plays a crucial role in harnessing the benefits of prickly pear fruit by utilizing betalain as natural colorants to replace artificial colors in model food systems. Prickly pear betalain-enriched gummies were developed using various sugar substitutes, including table sugar, xylitol, stevia, and fructo-oligosaccharides (FOS). These gummies were analyzed for in vitro enzymatic inhibition, anti-inflammatory effects and molecular docking studies for decoding diabetes type-II and skin resilience. FTIR and HPLC confirmed the presence of betalain and isorhamnetin across all gummies. FOS and stevia incorporated gummies exhibited the highest polyphenolics and antioxidant activity. Betalain extract combined with stevia and FOS showed significant in vitro enzyme inhibition compared to other studied gummies. Specifically, FOS gummies showed the highest inhibition rates for α-amylase (23.58 %), α-glucosidase (24.12 %), tyrosinase (54.68 %), and collagenase (2.38 %). Additionally, all samples were non-toxic to RAW cell lines and exhibited anti-inflammatory effects. Molecular docking studies corroborated the in vitro results, and pharmacokinetics profiling confirmed the gummies' suitability for oral consumption and skin safety. The developed prickly pear betalain-enriched gummies, particularly those formulated with fructo-oligosaccharides and stevia, demonstrate significant potential as functional supplements for managing diabetes type-II and skin-related conditions.

Discovery of 5-(Substituted Phenyl)-2-aryl Benzimidazole Derivatives as SIRT1 Activators: Their Design, in silico Studies, Synthesis, and in vitro Evaluation.

Silent information regulator two homologue one (SIRT1) is an emerging target for managing metabolic disorders. This study aimed to synthesize novel 5-(- substituted phenyl)-2-aryl benzimidazole derivatives and evaluate them for SIRT1 activation. The compounds were designed according to the findings of the QSAR models framed in our previous studies. Molecular docking and dynamics studies were also performed to explore the interactions of designed compounds with the active site of the SIRT1 enzyme using AutoDock Vina and Schrödinger Maestro version 11.8.012, respectively. Compounds with good binding affinity were synthesized by Suzuki-Miyaura cross-coupling and spectrally characterized. The molecules were evaluated for their in vitro SIRT1 activation properties using a fluorescent screening kit. Based on the results of in vitro assay, a structure-activity relationship was established. SwissADME was employed to calculate the pharmacokinetics characteristics of the synthesized molecules. The molecular docking studies revealed that all the activators were effectively docked in the catalytic active site. All compounds demonstrated interactions with important amino acids like Glu230 and Arg446. In molecular dynamics simulations, the root mean square deviation (RMSD) of compound 5m and protein SIRT1 remained stable, i.e., below 3mm. Compound 5m, 4-(2-(3,4-dihydroxy-5-nitrophenyl)-1H-benzo[d]imidazol- 5-yl)benzaldehyde, was the most potent compound with an EC50 value of 0.006 mM (±0.001) and maximum activation of 240.5%. All the synthesized compounds had acceptable theoretical ADME profiles, and drug-likeness properties complied with Lipinski's rule. According to the findings, synthesized compounds may be viable leads for SIRT1 activators and may be used to advance preclinical in vivo research utilizing animal models.

Tunisian wild rosemary (Rosmarinus officinalis) essential oils: phytochemical profiling, antibacterial and antibiofilm properties and molecular docking studies

Despite rapid advances in drug production, bacteria have adopted several drug resistance strategies, such as biofilm production. Therefore, research to develop and/or discover alternative antibacterial agents, such as natural products from plants becomes a necessity. Rosemary (Rosmarinus officinalis) is a well-known potent source of bioactive molecules with antibacterial and antibiofilm activities. The aim of this study was to determine the phytochemical composition, to evaluate the antibacterial and antibiofilm activities of Tunisian wild rosemary essential oils (REOs). Molecular docking tools were used to investigate the antibacterial effects of REOs bioactive molecules. GC-MS analysis revealed thirty-one compounds. The main components that define the chemotype were eucalyptol, camphor and α-pinene. The antibacterial activity evaluated by disc diffusion and the microdilution methods and the antibiofilm activity assessed by crystal violet test proved that REOs had strong activity against all the bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Salmonella typhimurium). The molecular docking study revealed that the investigated main compounds of REOs exhibited the best binding scores with two target proteins (Fts-Z and FimH). These results prove that REOs exhibited interesting biological activities as antibacterial and antibiofilm agents which could be explored for complementary medicine, food and pharmaceutical industries.