Alginate biopolymeric structures: Versatile carriers for bioactive compounds in functional foods and nutraceutical formulations: A review.

Alginate-based biopolymer products have gained attention for protecting and delivering bioactive components in nutraceuticals and functional foods. These naturally abundant anionic, unbranched, and linear copolymers are also produced commercially by microorganisms. Alone or in combination with other copolymers, they efficiently transport bioactive molecules in food and nutraceutical products. This review aims to provide an in-depth understanding of alginate-based products and structures, emphasizing their role in delivering functional molecules in various formulations and delivery systems. These include edible coatings/films, gels/emulsions, beads/droplets, microspheres/particles, and engineered nanostructures where alginates have been used potentially. By exploring these applications, readers gain insights into the benefits of these products. Because, alginate-based biopolymer products have shown promise in delivering bioactive compounds like vitamin C, vitamin D3, curcumin, ß-carotene, resveratrol, folic acid, gliadins, caffeic acid, betanin, limonoids, quercetin, several polyphenols and essential oils, etc., which are chief contributors to treating specific/overall nutritional and chronic metabolic disorders. So, this review summarizes the potential of alginate-based structures/products in various forms for delivering a wide range of functional food ingredients and nutraceutical components that offer promising perspectives for future investigations.

QSAR modeling, pharmacophore-based virtual screening, and ensemble docking insights into predicting potential epigallocatechin gallate (EGCG) analogs against epidermal growth factor receptor.

Epigallocatechin gallate (EGCG) is a major polyphenols of green tea may have the possibility to inhibit epidermal growth factor receptor (EGFR) activity and lead to reduce non-small cell lung cancer (NSCLC) progression. However, EGCG has some toxic features; moreover, there is a lack of explorations into the molecular interaction mechanisms of EGCG and the EGFR. In this examination, integration of quantitative structure-activity relationship (QSAR) modeling, pharmacophore-based virtual screening, and ensemble docking approaches were used to predict potential novel EGCG analogs as effective EGFR inhibitors. QSAR modeling of logP and logS predictions and toxicity endpoint investigation for a set of 82 compounds were shown good predictive ability and robustness from the applicability domain and confusion matrix elucidations. Virtual screening and docking studies revealed that seven high potential EGCG analogs as strong EGFR binders. Molecular interactions interpretations indicated some insights into the structural features of ligands that efficiently interfere with mutation possible residues (Gly719 and Thr790) of the EGFR. The hydrogen bonds, hydrophobic interactions, atomic π-cation interactions and salt bridges of ligands are contributing additional stability to receptor structure, which can lead to blocking the intracellular protein-tyrosine kinase activity, including EGFR associated pathways activation in NSCLC. Therefore, this can characterize as a block-cluster mechanism between EGCG analogs and EGFR complexes. In silico anti-EGFR and anticancer activity predictions suggested that, ligands could act as promising pharmacological, anticancer, and drug-like templates of EGFR towards moderating the NSCLC progressions. These results and provided pinpoints could be beneficial to recognize probable therapeutic targets for NSCLC therapy.

Structural Probing, Screening and Structure-Based Drug Repositioning Insights into the Identification of Potential Cox-2 Inhibitors from Selective Coxibs.

The rate-limiting enzyme cyclooxygenase-2 (COX-2) is considered as an insightful prognostic target for non-small cell lung cancer (NSCLC) therapy. Now, administration and prolonged utilization of selective COX-2 inhibitors (COXIBs) towards moderating the NSCLC has been associated with different side effects. In the present study, we focused on the structure-based drug repositioning approaches for predicting therapeutic potential de novo candidates for human COX-2. Due to discrepancies in the eminence of x-ray diffraction structures, creates a big barrier in drug discovery approach. Hence, the adaptable COX-2 structure was investigated using multi-template modeling method. Next, a dataset of twenty-six celebrex-associated optimized scaffolds were screened from ZINC database. Comparative docking approaches were then utilized to identify five compounds as best binders to the active site of COX-2 structures and strongly agree with enormous experimental consequences. MD simulations of regarded protein-ligand complexes reveals that lead molecules were stabilized dynamically in inside the cyclooxygenase site by forming potential salt bridges with Tyr348, Tyr385 and Ser530 residues. These significant results revealed that, identified druggables could prevent the tyrosyl radicals and prostaglandin production that reduces NSCLC progression. Furthermore, pharmacokinetics assets of respected ligands were analyzed, which incorporates similarity ensemble approach, druglikeness and ADMET properties. Finally, the identified novel candidates could serve as COX-2 inhibitors for NSCLC therapy, and coxibs are the best choices for designing new scaffolds to treat cyclooxygenases regard disorders.

In silico insights into the identification of potential novel angiogenic inhibitors against human VEGFR-2: a new SAR-based hierarchical clustering approach.

In this study, binding efficiency of new pyrrolopyrimidine structural analogs against human vascular endothelial growth factor receptor-2 (VEGFR-2) were elucidated using integrated in silico methods. Optimized high-resolution model of VEGFR-2 was generated and adopted for structure-based virtual screening approaches. Pyrrolopyrimidine inhibitor (CP15) associated compounds were screened from PubChem database and subjected to virtual screening and comparative docking methods against the receptor ligand-binding domain. Accordingly, high efficient compounds were clustered with similarity indices through PubChem structure cluster module using single-linkage algorithm. Moreover, pharmacokinetics including drug metabolism activities of high-binding leads under investigation was portrayed using ADMET and similarity ensemble analysis. Optimal energy orientations of the selected protein model have been shown to be reliable, and highly recommended for screening and docking studies. Docking and clustering strategies were shown that nineteen candidates as most effective binders for VEGFR-2 than CP15, and are grouped as three classes. Lys868, Glu885, Cys919, His1026, Arg1027, Asp1046, and Gly1048 residues were predicted as novel hotspot residues, and participate in H-bonds, π-cation, π-stacking, halogen bonds, and salt-bridges formation with ligands. These additional bonds are contributing extent stability that holds the receptor structure at flexible state, this make difficult to any further conformational changes for evoking angiogenic signals. The ADMET and similarity ensemble analysis results were strongly indicated that thirteen candidates as best ligands for angiogenesis targets. Altogether, these findings indicate potential angiogenic templates and their binding levels with VEGFR-2; sorted viewpoints could be useful as a promising way to describe potential angiogenesis inhibitors with related molecular targets.

In silico insights into prediction and analysis of potential novel pyrrolopyridine analogs against human MAPKAPK-2: a new SAR-based hierarchical clustering approach.

In the present study, we have focused on to elucidate potential bioactive pyrrolopyridine (PYP23) analogs against human mitogen-activated protein kinase-activated protein kinase-2 (MK-2). Here, in silico methods and computational systems biology tools were used as rational strategies to predict novel PYP23 analogs against the MK-2. Initially, crystal structure (PDB-ID: 2P3G) consists steriochemical conflicts were rectified by structure-optimization approaches using the Modeller program, and a new optimized-high resolution model was generated. The stereochemical qualities of the predicted MK-2 model were judged; these showed that the model was reliable for docking assessments. SAR-based bioactivity analysis showed that among the 197 datasets only 15 candidates contained bioactivity data and were accepted as probable MK-2 inhibitors. Virtual screening and docking strategies of dataset compounds against the ligand-binding domain of MK-2 recognized 13 composites containing high binding affinity than known compounds. Furthermore, the comparative structure clustering, in silico toxicogenomics and QSAR-based anticancer properties prediction approaches were successful in the recognition of five best potential compounds such as 60118340, 60118338, 60117736, 60118473 and 60118322, which have great anticancer and drug-likeness with non-toxicity class indices. Leu70, Glu139, Leu141, Glu145, Glu190, Thr206 and Asp207 were found to be novel hotspot residues prominently involved in H-bonds framing with ligands. Interestingly, they have shown better molecular similarity with known bioactive PYP inhibitors. Thus, predicted five compounds can useful as possible chemotherapeutic agents for MK-2 and show similar molecular actions like known PYP inhibitors. Overall, these streamlined new methods may have great potential to reveal possible ligands toward other molecular targets and biomarkers.

Computational screening, ensemble docking and pharmacophore analysis of potential gefitinib analogues against epidermal growth factor receptor.

The observable mutated isoforms of epidermal growth factor receptor (EGFR) are important considerable therapeutic benchmarks in moderating the non-small cell lung cancer (NSCLC). Recently, quinazoline-based ATP competitive inhibitors have been developed against the EGFR; however, these imply the mutation probabilities, which contribute to the discovery of high probable novel inhibitors for EGFR mutants. Therefore, SAR-based bioactivity analysis, molecular docking and computational toxicogenomics approaches were performed to identify and evaluate new analogs of gefitinib against the ligand-binding domain of the EGFR double-mutated model. From the diverse groups of molecular clustering and molecular screening strategies, top high-binding gefitinib-analogues were identified and studied against EGFR core cavity through three-phase ensemble docking approach. Resulted high possible leads showed good binding orientations than gefitinib (positive control) thus they were subjected to pharmacophore analysis that possesses possible molecular assets to tight binding with EGFR domain. Residues Ser720, Arg841 and Trp880 were observed as novel hot spots and involved in H-bonds, pi-stacking and π-cation interactions that contribute additional electrostatic potency to sustain stability and complexity of protein-ligand complexes, thus they have ability to profoundly adopted by pharmacophoric features. Furthermore, lead molecules have an inhibition percent probability, anticancer potency, toxic impacts, flexible pharmacokinetics, potential gene-chemical interactions towards EGFR were revealed by computational systems biology tools. Our multiple screening strategies confirmed that the druggable sub-pocket was crucial to strong EGFR-ligand binding. The essential pharmacophoric features of ligands provided viewpoints for new inhibitors envisaging, and predicted scaffolds could used as anticancer agents against selected EGFR mutated isoforms.

Ligand-based virtual screening, molecular docking, QSAR and pharmacophore analysis of quercetin-associated potential novel analogs against epidermal growth factor receptor.

The present study was to explore expectation and examination of therapeutic potential quercetin analogs as efficient anticancer agents against human epidermal growth factor receptor (EGFR), which is a consistent hallmark for moderating the non-small-cell lung carcinoma (NSCLC). Here, ligand-based virtual screening, pharmacophore approach and molecular docking were established as rational strategies for recognition of small analogs against the ligand binding domain of EGFR (PDB code: 1XKK). Adverse effects, toxicogenomics and pharmacokinetics reported that 10 candidates showed reliable consequences with less side effects and more efficient for target receptor. Protein-ligand interaction profiles revealed that the probable H-bonds, atomic-π contacts, salt bridges and van der Waals interactions sustain the complexity and stability of receptor structure; thus, they could complicate to generate single alteration acquired for drug resistance. In silico anticancer properties explain the lead scaffolds which are assumed to be flexible and experimentally proved chemicals. The overall consequences indicated that recognized leads could be utilized as reference skeletons for new inhibitors envisaging toward EGFR to ameliorate NSCLC and other malignant disorders.