Displaying publications 21 - 40 of 729 in total

Abstract:
Sort:
  1. Pharmacophore Modelling and Virtual Screening Studies for the Discovery of Potential Natural Products Based PDE1B Inhibitor Lead Compounds
    Shy TW, Gaurav A
    Cent Nerv Syst Agents Med Chem, 2021;21(3):195-204.
    PMID: 34970959 DOI: 10.2174/1871524922666211231115638
    AIM: The aim of the present study was to apply pharmacophore based virtual screening to a natural product database to identify potential PDE1B inhibitor lead compounds for neurodegenerative and neuropsychiatric disorders.

    BACKGROUND: Neurodegenerative and neuropsychiatric disorders are a major health burden globally. The existing therapies do not provide optimal relief and are associated with substantial adverse effects. This has resulted in a huge unmet medical need for newer and more effective therapies for these disorders. Phosphodiesterase (PDEs) enzymes have been identified as potential targets of drugs for neurodegenerative and neuropsychiatric disorders, and one of the subtypes, i.e., PDE1B, accounts for more than 90 % of total brain PDE activity associated with learning and memory process, making it an interesting drug target for the treatment of neurodegenerative disorders.

    OBJECTIVES: The present study has been conducted to identify potential PDE1B inhibitor lead compounds from the natural product database.

    METHODS: Ligand-based pharmacophore models were generated and validated; they were then employed for virtual screening of Universal Natural Products Database (UNPD) followed by docking with PDE1B to identify the best hit compound.

    RESULTS: Virtual screening led to the identification of 85 compounds which were then docked into the active site of PDE1B. Out of the 85 compounds, six showed a higher affinity for PDE1B than the standard PDE1B inhibitors. The top scoring compound was identified as Cedreprenone.

    CONCLUSION: Virtual screening of UNPD using Ligand based pharmacophore led to the identification of Cedreprenone, a potential new natural PDE1B inhibitor lead compound.

    Matched MeSH terms: Molecular Docking Simulation
  2. Computational Approaches in the Discovery and Development of Therapeutic and Prophylactic Agents for Viral Diseases
    Gaurav A, Agrawal N, Al-Nema M, Gautam V
    Curr Top Med Chem, 2022;22(26):2190-2206.
    PMID: 36278463 DOI: 10.2174/1568026623666221019110334
    Over the last two decades, computational technologies have played a crucial role in antiviral drug development. Whenever a virus spreads and becomes a threat to global health, it brings along the challenge of developing new therapeutics and prophylactics. Computational drug and vaccine discovery has evolved quickly over the years. Some interesting examples of computational drug discovery are anti-AIDS drugs, where HIV protease and reverse transcriptase have been targeted by agents developed using computational methods. Various computational methods that have been applied to anti-viral research include ligand-based methods that rely on known active compounds, i.e., pharmacophore modeling, machine learning or classical QSAR; structure-based methods that rely on an experimentally determined 3D structure of the targets, i.e., molecular docking and molecular dynamics and methods for the development of vaccines such as reverse vaccinology; structural vaccinology and vaccine epitope prediction. This review summarizes these approaches to battle viral diseases and underscores their importance for anti-viral research. We discuss the role of computational methods in developing small molecules and vaccines against human immunodeficiency virus, yellow fever, human papilloma virus, SARS-CoV-2, and other viruses. Various computational tools available for the abovementioned purposes have been listed and described. A discussion on applying artificial intelligence-based methods for antiviral drug discovery has also been included.
    Matched MeSH terms: Molecular Docking Simulation
  3. Sustainable lignocellulose fractionation by integrating p-toluenesulfonic acid/pentanol pretreatment with mannitol for efficient production of glucose, native-like lignin, and furfural
    Madadi M, Elsayed M, Sun F, Wang J, Karimi K, Song G, et al.
    Bioresour Technol, 2023 Mar;371:128591.
    PMID: 36627085 DOI: 10.1016/j.biortech.2023.128591
    A new cutting-edge lignocellulose fractionation technology for the co-production of glucose, native-like lignin, and furfural was introduced using mannitol (MT)-assisted p-toluenesulfonic acid/pentanol pretreatment, as an eco-friendly process. The addition of optimized 5% MT in pretreatment enhanced the delignification rate by 29% and enlarged the surface area and biomass porosity by 1.07-1.80 folds. This increased the glucose yield by 45% (from 65.34 to 94.54%) after enzymatic hydrolysis relative to those without MT. The extracted lignin in the organic phase of pretreatment exhibited β-O-4 bonds (61.54/100 Ar) properties of native cellulosic enzyme lignin. Lignin characterization and molecular docking analyses revealed that the hydroxyl tails of MT were incorporated with lignin and formed etherified lignin, which preserved high lignin integrity. The solubilized hemicellulose (96%) in the liquid phase of pretreatment was converted into furfural with a yield of 83.99%. The MT-assisted pretreatment could contribute to a waste-free biorefinery pathway toward a circular bioeconomy.
    Matched MeSH terms: Molecular Docking Simulation
  4. Fulltext Molecular Dynamics Simulations Reveal Novel Interacting Regions of Human Prion Protein to Brucella abortus Hsp60 Protein
    Le-Dao HA, Dinh TT, Tran TL, Lee VS, Tran-Van H
    Mol Biotechnol, 2024 Apr;66(4):687-695.
    PMID: 36633832 DOI: 10.1007/s12033-023-00655-9
    The distinctive morphology characteristics of microfold cells (M cells) allow the vaccine antigen not only to interact with immune cells directly, but also to effectively stimulate mucosal immune responses via receptors on its apical surface. Human prion protein, a transmembrane receptor for Brucella abortus Hsp60, is highly expressed on the M cell surface. Nonetheless, this protein tends to express in inclusion body in prokaryotic hosts. In this study, the shorter interacting regions of human prion protein were identified via computational methods such as docking and molecular dynamics simulations to minimize its aggregation tendency. The computational calculations revealed three novel human prion protein-interacting regions, namely PrP125, PrP174, and PrP180. In accordance with in silico prediction, the biologically synthesized peptides fusing with GST tag demonstrated their specific binding to Hsp60 protein via pull-down assay. Hence, this finding laid the groundwork for M-cell targeting candidate validation through these newly identified interacting regions.
    Matched MeSH terms: Molecular Docking Simulation
  5. An integrated assessment of ecological and human health risks of per- and polyfluoroalkyl substances through toxicity prediction approaches
    Hamid N, Junaid M, Manzoor R, Sultan M, Chuan OM, Wang J
    Sci Total Environ, 2023 Dec 20;905:167213.
    PMID: 37730032 DOI: 10.1016/j.scitotenv.2023.167213
    Per- and polyfluoroalkyl substances (PFAS) are also known as "forever chemicals" due to their persistence and ubiquitous environmental distribution. This review aims to summarize the global PFAS distribution in surface water and identify its ecological and human risks through integrated assessment. Moreover, it provides a holistic insight into the studies highlighting the human biomonitoring and toxicological screening of PFAS in freshwater and marine species using quantitative structure-activity relationship (QSAR) based models. Literature showed that PFOA and PFOS were the most prevalent chemicals found in surface water. The highest PFAS levels were reported in the US, China, and Australia. The TEST model showed relatively low LC50 of PFDA and PFOS for Pimephales promelas (0.36 and 0.91 mg/L) and high bioaccumulation factors (518 and 921), revealing an elevated associated toxicity. The risk quotients (RQs) values for P. promelas and Daphnia magna were found to be 269 and 23.7 for PFOS. Studies confirmed that long-chain PFAS such as PFOS and PFOA undergo bioaccumulation in aquatic organisms and induce toxicological effects such as oxidative stress, transgenerational epigenetic effects, disturbed genetic and enzymatic responses, perturbed immune system, hepatotoxicity, neurobehavioral toxicity, altered genetic and enzymatic responses, and metabolism abnormalities. Human biomonitoring studies found the highest PFOS, PFOA, and PFHxS levels in urine, cerebrospinal fluid, and serum samples. Further, long-chain PFOA and PFOS exposure create severe health implications such as hyperuricemia, reduced birth weight, and immunotoxicity in humans. Molecular docking analysis revealed that short-chain PFBS (-11.84 Kcal/mol) and long-chain PFUnDA (-10.53 Kcal/mol) displayed the strongest binding interactions with human serum albumin protein. Lastly, research challenges and future perspectives for PFAS toxicological implications were also discussed, which helps to mitigate associated pollution and ecological risks.
    Matched MeSH terms: Molecular Docking Simulation
  6. Fulltext Pharmacotherapeutic Potential of Natural Products to Target the SARS-CoV-2 PLpro Using Molecular Screening and Simulation Approaches
    Sayaf AM, Ahmad H, Aslam MA, Ghani SA, Bano S, Yousafi Q, et al.
    Appl Biochem Biotechnol, 2023 Nov;195(11):6959-6978.
    PMID: 36961512 DOI: 10.1007/s12010-023-04466-1
    Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development. To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120-140, 160-180, and 205-215. The 120-140 and 160-180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be - 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was - 35.58 ± 0.14 kcal/mol, for the NPC474594-PLpro, the TBE was - 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be - 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes.
    Matched MeSH terms: Molecular Docking Simulation
  7. Fulltext Identification of Potential Biomarkers and Small Molecule Drugs for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ): An Integrated Bioinformatics Study Using Big Data
    Balachandran K, Ramli R, Karsani SA, Abdul Rahman M
    Int J Mol Sci, 2023 May 11;24(10).
    PMID: 37239981 DOI: 10.3390/ijms24108635
    This study aimed to identify potential molecular mechanisms and therapeutic targets for bisphosphonate-related osteonecrosis of the jaw (BRONJ), a rare but serious side effect of bisphosphonate therapy. This study analyzed a microarray dataset (GSE7116) of multiple myeloma patients with BRONJ (n = 11) and controls (n = 10), and performed gene ontology, a pathway enrichment analysis, and a protein-protein interaction network analysis. A total of 1481 differentially expressed genes were identified, including 381 upregulated and 1100 downregulated genes, with enriched functions and pathways related to apoptosis, RNA splicing, signaling pathways, and lipid metabolism. Seven hub genes (FN1, TNF, JUN, STAT3, ACTB, GAPDH, and PTPRC) were also identified using the cytoHubba plugin in Cytoscape. This study further screened small-molecule drugs using CMap and verified the results using molecular docking methods. This study identified 3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo[d]isoxazol-6-yl) methoxy) phenyl) propanoic acid as a potential drug treatment and prognostic marker for BRONJ. The findings of this study provide reliable molecular insight for biomarker validation and potential drug development for the screening, diagnosis, and treatment of BRONJ. Further research is needed to validate these findings and develop an effective biomarker for BRONJ.
    Matched MeSH terms: Molecular Docking Simulation
  8. Reverse vaccinology-based prediction of a multi-epitope SARS-CoV-2 vaccine and its tailoring to new coronavirus variants
    Ezzemani W, Kettani A, Sappati S, Kondaka K, El Ossmani H, Tsukiyama-Kohara K, et al.
    J Biomol Struct Dyn, 2023 Jul;41(11):4917-4938.
    PMID: 35549819 DOI: 10.1080/07391102.2022.2075468
    The genome feature of SARS-CoV-2 leads the virus to mutate and creates new variants of concern. Tackling viral mutations is also an important challenge for the development of a new vaccine. Accordingly, in the present study, we undertook to identify B- and T-cell epitopes with immunogenic potential for eliciting responses to SARS-CoV-2, using computational approaches and its tailoring to coronavirus variants. A total of 47 novel epitopes were identified as immunogenic triggering immune responses and no toxic after investigation with in silico tools. Furthermore, we found these peptide vaccine candidates showed a significant binding affinity for MHC I and MHC II alleles in molecular docking investigations. We consider them to be promising targets for developing peptide-based vaccines against SARS-CoV-2. Subsequently, we designed two efficient multi-epitopes vaccines against the SARS-CoV-2, the first one based on potent MHC class I and class II T-cell epitopes of S (FPNITNLCPF-NYNYLYRLFR-MFVFLVLLPLVSSQC), M (MWLSYFIASF-GLMWLSYFIASFRLF), E (LTALRLCAY-LLFLAFVVFLLVTLA), and N (SPRWYFYYL-AQFAPSASAFFGMSR). The second candidate is the result of the tailoring of the first designed vaccine according to three classes of SARS-CoV-2 variants. Molecular docking showed that the protein-protein binding interactions between the vaccines construct and TLR2-TLR4 immune receptors are stable complexes. These findings confirmed that the final multi-epitope vaccine could be easily adapted to new viral variants. Our study offers a shortlist of promising epitopes that can accelerate the development of an effective and safe vaccine against the virus and its adaptation to new variants.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Molecular Docking Simulation
  9. Phillyrin: an adipose triglyceride lipase inhibitor supported by molecular docking, dynamics simulation, and pharmacological validation
    Zhou C, Yan L, Xu J, Hamezah HS, Wang T, Du F, et al.
    J Mol Model, 2024 Feb 13;30(3):68.
    PMID: 38347278 DOI: 10.1007/s00894-024-05875-7
    CONTEXT: Adipose triglyceride lipase (ATGL), a key enzyme responsible for lipolysis, catalyzes the first step of lipolysis and converts triglycerides to diacylglycerols and free fatty acids (FFA). Our previous work suggested that phillyrin treatment improves insulin resistance in HFD-fed mice, which was associated with ATGL inhibition. In this study, using docking simulation, we explored the binding pose of phillyrin and atglistatin (a mouse ATGL inhibitor) to ATGL in mouse. From the docking results, the interactions with Ser47 and Asp166 were speculated to have caused phillyrin to inhibit ATGL in mice. Further, molecular dynamics simulation of 100 ns and MM-GBSA were conducted for the protein-ligand complex, which indicated that the system was stable and that phillyrin displayed a better affinity to ATGL than did atglistatin throughout the simulation period. Moreover, the results of pharmacological validation were consistent with those of the in silico simulations. In summary, our study illustrates the potential of molecular docking to accurately predict the binding protein produced by AlphaFold and suggests that phillyrin is a potential small molecule that targets and inhibits ATGL enzymatic activity.

    METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrödinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.

    Matched MeSH terms: Molecular Docking Simulation
  10. Mechanistic insight of α-mangostin encapsulation in 2-hydroxypropyl-β-cyclodextrin for solubility enhancement
    Muchtaridi M, Triwahyuningtyas D, Muhammad Fakih T, Megantara S, Choi SB
    J Biomol Struct Dyn, 2024 Apr;42(6):3223-3232.
    PMID: 37286382 DOI: 10.1080/07391102.2023.2214237
    α-Mangostin is the most abundant compound contained in the mangostin (Garcinia mangostana L.) plant which have been developed and proven to have many promising pharmacological effects. However, the low water solubility of α-mangostin causes limitations in its development in clinical purpose. To increase the solubility of a compound, a method currently being developed is to make drug inclusion complexes using cyclodextrins. This research aimed to use in silico techniques namely molecular docking study and molecular dynamics simulation to explore the molecular mechanism and stability of the encapsulation of α-mangostin using cyclodextrins. Two types of cyclodextrins were used including β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin docked against α-mangostin. From the molecular docking results, it shows that the α-mangostin complex with 2-hydroxypropyl-β-cyclodextrin provides the lowest binding energy value of -7.99 Kcal/mol compared to β-cyclodextrin value of -6.14 Kcal/mol. The α-mangostin complex with 2-hydroxypropyl-β-cyclodextrin also showed good stability based on molecular dynamics simulation during 100 ns. From molecular motion, RDF, Rg, SASA, density, total energy analyzes, this complex shows increased solubility in water and provided good stability. This indicates that the encapsulation of α-mangostin with 2-hydroxypropyl-β-cyclodextrin can increase the solubility of the α-mangostin.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Molecular Docking Simulation
  11. Fulltext A data-driven machine learning approach for discovering potent LasR inhibitors
    Koh CMM, Ping LSY, Xuan CHH, Theng LB, San HS, Palombo EA, et al.
    Bioengineered, 2023 Dec;14(1):2243416.
    PMID: 37552115 DOI: 10.1080/21655979.2023.2243416
    The rampant spread of multidrug-resistant Pseudomonas aeruginosa strains severely threatens global health. This severity is compounded against the backdrop of a stagnating antibiotics development pipeline. Moreover, with many promising therapeutics falling short of expectations in clinical trials, targeting the las quorum sensing (QS) system remains an attractive therapeutic strategy to combat P. aeruginosa infection. Thus, our primary goal was to develop a drug prediction algorithm using machine learning to identify potent LasR inhibitors. In this work, we demonstrated using a Multilayer Perceptron (MLP) algorithm boosted with AdaBoostM1 to discriminate between active and inactive LasR inhibitors. The optimal model performance was evaluated using 5-fold cross-validation and test sets. Our best model achieved a 90.7% accuracy in distinguishing active from inactive LasR inhibitors, an area under the Receiver Operating Characteristic Curve value of 0.95, and a Matthews correlation coefficient value of 0.81 when evaluated using test sets. Subsequently, we deployed the model against the Enamine database. The top-ranked compounds were further evaluated for their target engagement activity using molecular docking studies, Molecular Dynamics simulations, MM-GBSA analysis, and Free Energy Landscape analysis. Our data indicate that several of our chosen top hits showed better ligand-binding affinities than naringenin, a competitive LasR inhibitor. Among the six top hits, five of these compounds were predicted to be LasR inhibitors that could be used to treat P. aeruginosa-associated infections. To our knowledge, this study provides the first assessment of using an MLP-based QSAR model for discovering potent LasR inhibitors to attenuate P. aeruginosa infections.
    Matched MeSH terms: Molecular Docking Simulation
  12. Fulltext Profiling the Antidiabetic Potential of Compounds Identified from Fractionated Extracts of Entada africana toward Glucokinase Stimulation: Computational Insight
    Onikanni SA, Lawal B, Munyembaraga V, Bakare OS, Taher M, Khotib J, et al.
    Molecules, 2023 Jul 30;28(15).
    PMID: 37570723 DOI: 10.3390/molecules28155752
    Glucokinase plays an important role in regulating the blood glucose level and serves as an essential therapeutic target in type 2 diabetes management. Entada africana is a medicinal plant and highly rich source of bioactive ligands with the potency to develop new target drugs for glucokinase such as diabetes and obesity. Therefore, the study explored a computational approach to predict identified compounds from Entada africana following its intermolecular interactions with the allosteric binding site of the enzymes. We retrieved the three-dimensional (3D) crystal structure of glucokinase (PDB ID: 4L3Q) from the online protein data bank and prepared it using the Maestro 13.5, Schrödinger Suite 2022-3. The compounds identified were subjected to ADME, docking analysis, pharmacophore modeling, and molecular simulation. The results show the binding potential of the identified ligands to the amino acid residues, thereby suggesting an interaction of the amino acids with the ligand at the binding site of the glucokinase activator through conventional chemical bonds such as hydrogen bonds and hydrophobic interactions. The compatibility of the molecules was highly observed when compared with the standard ligand, thereby leading to structural and functional changes. Therefore, the bioactive components from Entada africana could be a good driver of glucokinase, thereby paving the way for the discovery of therapeutic drugs for the treatment of diabetes and its related complications.
    Matched MeSH terms: Molecular Docking Simulation
  13. Essential oil composition, anti-tyrosinase activity, and molecular docking studies of Knema intermedia Warb. (Myristicaceae)
    Salihu AS, Salleh WMNHW, Setzer WN
    Z Naturforsch C J Biosci, 2023 Jul 26;78(7-8):293-298.
    PMID: 36960928 DOI: 10.1515/znc-2023-0003
    Knema is one of the genera in the Myristicaceae family. The genus includes 60 species in Southeast Asia and is traditionally used for treating skin disorders. Here, for the first time, the essential oil, anti-tyrosinase, and molecular docking studies of Knema intermedia were evaluated. The essential oil was obtained by hydrodistillation and fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Anti-tyrosinase activity was evaluated against mushroom tyrosinase, whereas molecular docking studies were performed using Autodock vina embedded in PyRx to evaluate the binding interactions of major components. A total of 37 components (97.3%) were successfully identified in the essential oil, which was characterized by high amounts of t-muurolol (20.1%), α-copaene (14.4%), δ-cadinene (13.9%), germacrene B (9.5%), and δ-selinene (7.0%). The essential oil displayed moderate inhibitory activity towards tyrosinase with an IC50 value of 70.2 μg/mL. The best docking energy was observed with δ-selinene (-7.8 kcal/mol), and it also forms interactions with His85, His263, and His244 which are important amino acid residues of the tyrosinase receptor. Hence, this study provides valuable scientific data on K. intermedia as potential candidate for the development of natural antiaging formulations.
    Matched MeSH terms: Molecular Docking Simulation
  14. Development and application of fragment-based de novo inhibitor design approaches against Plasmodium falciparum GST
    Al-Qattan MNM, Mordi MN
    J Mol Model, 2023 Aug 16;29(9):281.
    PMID: 37584781 DOI: 10.1007/s00894-023-05650-0
    CONTEXT: Modulation of disease progression is frequently started by identifying biochemical pathway catalyzed by biomolecule that is prone to inhibition by small molecular weight ligands. Such ligands (leads) can be obtained from natural resources or synthetic libraries. However, de novo design based on fragments assembly and optimization is showing increasing success. Plasmodium falciparum parasite depends on glutathione-S-transferase (PfGST) in buffering oxidative heme as an approach to resist some antimalarials. Therefore, PfGST is considered an attractive target for drug development. In this research, fragment-based approaches were used to design molecules that can fit to glutathione (GSH) binding site (G-site) of PfGST.

    METHODS: The involved approaches build molecules from fragments that are either isosteric to GSH sub-moieties (ligand-based) or successfully docked to GSH binding sub-pockets (structure-based). Compared to reference GST inhibitor of S-hexyl GSH, ligands with improved rigidity, synthetic accessibility, and affinity to receptor were successfully designed. The method involves joining fragments to create ligands. The ligands were then explored using molecular docking, Cartesian coordinate's optimization, and simplified free energy determination as well as MD simulation and MMPBSA calculations. Several tools were used which include OPENEYE toolkit, Open Babel, Autodock Vina, Gromacs, and SwissParam server, and molecular mechanics force field of MMFF94 for optimization and CHARMM27 for MD simulation. In addition, in-house scripts written in Matlab were used to control fragments connection and automation of the tools.

    Matched MeSH terms: Molecular Docking Simulation
  15. Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors
    Roney M, Huq AKMM, Issahaku AR, Soliman MES, Hossain MS, Mustafa AH, et al.
    J Biomol Struct Dyn, 2023;41(21):12186-12203.
    PMID: 36645141 DOI: 10.1080/07391102.2023.2166123
    Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue therapies. This research's primary objective was to discover an anti-DENV inhibitor using in silico ligand- and structure-based approaches. To begin, a ligand-based pharmacophore model was developed, and 130 distinct natural products (NPs) were screened. Docking of the pharmacophore-matched compounds were performed to the active site of DENV-2 RdRp protease . Eleven compounds were identified as potential DENV-2 RdRp inhibitors based on docking energy and binding interactions. ADMET and drug-likeness were done to predict their pharmacologic, pharmacokinetic, and drug-likeproperties . Compounds ranked highest in terms of pharmacokinetics and drug-like appearances were then subjected to additional toxicity testing to determine the leading compound. Additionally, MD simulation of the lead compound was performed to confirm the docked complex's stability and the binding site determined by docking. As a result, the lead compound (compound-108) demonstrated an excellent match to the pharmacophore, a strong binding contact and affinity for the RdRp enzyme, favourable pharmacokinetics, and drug-like characteristics. In summary, the lead compound identified in this study could be a possible DENV-2 RdRp inhibitor that may be further studied on in vitro and in vivo models to develop as a drug candidate.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Molecular Docking Simulation
  16. Skin hydration modulatory activities of Ficus deltoidea extract
    Ariffin NHM, Hasham R, Hamzah MAAM, Park CS
    Fitoterapia, 2024 Jan;172:105755.
    PMID: 38000761 DOI: 10.1016/j.fitote.2023.105755
    Ficus deltoidea was known for its potent antioxidant, anti-melanogenic and photoprotective skin barrier activities. These properties are contributed by its biomarkers which are vitexin and isovitexin. This study aims to optimize the yield of methanolic extraction of Ficus deltoidea leaves (EFD) and evaluate their effects on skin barrier function and hydration. For optimization, Box-Behnken design was utilized to investigate the effects of methanol concentration, sonication time, and solvent-to-sample ratio on the yields of vitexin and isovitexin in EFD. The optimal yields obtained were 32.29 mg/g for vitexin and 35.87 mg/g for isovitexin. The optimum extraction conditions were 77.66% methanol concentration, 20.03 min sonication time, and 19.88 mL/g solvent-to-sample ratio. The quantitative real-time polymerase chain reaction was utilized to measure variant marker genes of transglutaminase-1, caspase 14, ceramide synthase 3, involucrin, and filaggrin of EFD-induced keratinocyte differentiation by in vitro study. Exposure to EFD has elevated the mRNA levels of all tested marker genes by 0.7-9.2 folds. Then, in vivo efficacy study was conducted on 20 female subjects for 14 days to evaluate skin biophysical assessment of hydration. EFD topical formulation treatment successfully increased skin hydration on day 7 (43.74%) and day 14 (47.23%). In silico study by molecular docking was performed to identify intermolecular binding interactions of vitexin and isovitexin with the interested proteins of tested marker genes. The result of molecular docking to the interested proteins revealed a similar trend with real-time PCR data. In conclusion, EFD potentially enhanced the skin barrier function and hydration of human skin cells.
    Matched MeSH terms: Molecular Docking Simulation
  17. Fortunefuroic Acid J from Keteleeria Hainanensis and its Dual Inhibitory Effects on ATP-Citrate Lyase and Acetyl-CoA Carboxylase
    Zhao ZY, Zang Y, Li J, Choo YM, Xiong J, Hu JF
    Chem Biodivers, 2024 Dec;21(12):e202401520.
    PMID: 39221607 DOI: 10.1002/cbdv.202401520
    A previously undescribed triterpenoid (fortunefuroic acid J, 1) was isolated from the endangered conifer Keteleeria hainanensis, along with 20 other known terpenoids. Compound 1 is characterized by an unusual 3,4-seco-9βH-lanost-3-oic acid motif, featuring a rare furoic acid moiety in its lateral chain. The structure elucidation of this compound was achieved through a combination of spectroscopic and computational methods. The C-15 epimers of 15-methoxypinusolidic acid (15R-8 and 15S-9) were successfully separated and identified for the first time. Compound 1 demonstrated dual inhibitory effects against ATP-citrate lyase (ACL, IC50: 0.92 μM) and acetyl-CoA carboxylase 1 (ACC1, IC50: 10.76 μM). Compounds 2 and 11 exclusively inhibited ACL, exhibiting IC50 values of 2.64 and 6.35 μM, respectively. Compound 1 is classified among the fortunefuroic acid-type compounds, previously isolated from K. fortunei, distinguished by the presence of a rare furoic acid moiety in their lateral chain. The chemotaxonomic significance of the 9βH-lanost-26-oic acids in Keteleeria was briefly discussed. These findings highlight the importance of conserving plant species diversity, thereby enhancing the exploration of structurally diverse compounds and potential avenues for developing new therapeutics targeting ACL/ACC1-associated diseases.
    Matched MeSH terms: Molecular Docking Simulation
  18. Fulltext Computer aided screening of secreted frizzled-related protein 4 (SFRP4): a potential control for diabetes mellitus
    Bukhari SA, Shamshari WA, Ur-Rahman M, Zia-Ul-Haq M, Jaafar HZ
    Molecules, 2014 Jul 11;19(7):10129-36.
    PMID: 25019556 DOI: 10.3390/molecules190710129
    Diabetes mellitus is a life threatening disease and scientists are doing their best to find a cost effective and permanent treatment of this malady. The recent trend is to control the disease by target base inhibiting of enzymes or proteins. Secreted frizzled-related protein 4 (SFRP4) is found to cause five times more risk of diabetes when expressed above average levels. This study was therefore designed to analyze the SFRP4 and to find its potential inhibitors. SFRP4 was analyzed by bio-informatics tools of sequence tool and structure tool. A total of three potential inhibitors of SFRP4 were found, namely cyclothiazide, clopamide and perindopril. These inhibitors showed significant interactions with SFRP4 as compared to other inhibitors as well as control (acetohexamide). The findings suggest the possible treatment of diabetes mellitus type 2 by inhibiting the SFRP4 using the inhibitors cyclothiazide, clopamide and perindopril.
    Matched MeSH terms: Molecular Docking Simulation*
  19. Fulltext Synthesis, spectroscopic investigations (X-ray, NMR and TD-DFT), antimicrobial activity and molecular docking of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone
    Barakat A, Ghabbour HA, Al-Majid AM, Soliman SM, Ali M, Mabkhot YN, et al.
    Molecules, 2015;20(7):13240-63.
    PMID: 26197312 DOI: 10.3390/molecules200713240
    The synthesis of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone 1 is described. The molecular structure of the title compound 1 was confirmed by NMR, FT-IR, MS, CHN microanalysis, and X-ray crystallography. The molecular structure was also investigated by a set of computational studies and found to be in good agreement with the experimental data obtained from the various spectrophotometric techniques. The antimicrobial activity and molecular docking of the synthesized compound was investigated.
    Matched MeSH terms: Molecular Docking Simulation*
  20. Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
    Taha M, Imran S, Alomari M, Rahim F, Wadood A, Mosaddik A, et al.
    Bioorg Med Chem, 2019 07 15;27(14):3145-3155.
    PMID: 31196753 DOI: 10.1016/j.bmc.2019.05.049
    A new series of oxadiazole with thiadiazole moiety (6-27) were synthesized, characterized by different spectroscopic techniques and evaluated for β-glucuronidase inhibitory potential. Sixteen analogs such as 6, 7, 8, 9, 10, 12, 13, 14, 17, 18, 20, 23, 24, 25, 26 and 27 showed IC50 values in the range of 0.96 ± 0.01 to 46.46 ± 1.10 μM, and hence were found to have excellent inhibitory potential in comparison to standard d-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Two analogs such as 16 and 19 showed moderate inhibitory potential while analogs 11, 15, 21 and 22 were found inactive. Our study identifies new series of potent β-glucuronidase inhibitors for further investigation. Structure activity relationships were established for all compounds which showed that the activity is varied due to different substituents on benzene ring. The interaction of the compounds with enzyme active site were confirmed with the help of docking studies, which reveals that the electron withdrawing group and hydroxy group make the molecules more favorable for enzyme inhibition.
    Matched MeSH terms: Molecular Docking Simulation/methods*
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links