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  1. Acetogenins Exhibit Potential BCL-XL Inhibitor for the Induction of Apoptosis in the Molecular Docking Study
    Nordin N, Khimani K, Abd Ghani MF
    Curr Drug Discov Technol, 2021;18(6):e010921191171.
    PMID: 33563198 DOI: 10.2174/1570163818666210204202426
    BACKGROUND: Anti-apoptotic protein BCL-XL plays a vital role in tumorigenesis and cancer chemotherapy resistance, resulting in a good target for cancer treatment. Understanding the function of BCL-XL has driven the progression of a new class of cancer drugs that can mimic its natural inhibitors, BH3-only proteins, to trigger apoptosis. This mimicking is initiated through acetogenins due to their excellent biological properties. Acetogenins, which can be isolated from Annonaceae plants, have a unique structure along with several oxygenated functionalities.

    OBJECTIVE: Based on their biological capability, various acetogenins were studied in the present study and compared alongside ABT-737 on molecular docking.

    METHODS: The docking simulation of acetogenins was performed using AutoDock Vina software.

    RESULTS: Our findings have shown eleven acetogenins-BCL-XL protein complex, namely, muricin B (2), muricin F (4), muricin H (6), muricin I (7), xylomaticin (9), annomontacin (12), annonacin (14), squamocin (15), squamostatin A (16), bullatacin (20) and annoreticulin (21) exhibited strong binding affinities lower than - 10.4 kcalmol-1 as compared to ABT-373-BCL-XL complex. Six hydrogen bonds along with hydrophobic interaction were detected on the complex of BCL-XL with muricin B (2), muricin G (5), corossolone (11), and isoannonacin-10-one A (18).

    CONCLUSION: These findings indicated that some acetogenins could represent a new potential BCLXL inhibitor that could mimic the BH3-only protein for the induction of apoptosis in cancer chemotherapy.

    Matched MeSH terms: Molecular Docking Simulation
  2. Fulltext Synthesis, in-Vitro and in Silico Studies of Azo-Based Calix[4]arenes as Antibacterial Agent and Neuraminidase Inhibitor: A New Look Into an Old Scaffold
    Ali Y, Muhamad Bunnori N, Susanti D, Muhammad Alhassan A, Abd Hamid S
    Front Chem, 2018;6:210.
    PMID: 29946538 DOI: 10.3389/fchem.2018.00210
    Calixarene derivatives are reported as potential therapeutic agents. Azo derivatives of calixarenes have not been given much consideration to explore their biomedical applications. In the present study, some azo-based derivatives of calix[4]arene were synthesized and characterized and their antibacterial and antiviral potentials were studied. The mono azo products of sulphanilamide, sulfaguanidine and 2-methyl-4-aminobenzoic acid showed good activity against bacterial strains with minimum inhibition concentration values ranging from 0.97 to 62.5 μg/mL. For mono azo products, the diazotized salt was applied as a limiting reagent. The use of calix[4]arene and sodium acetate trihydrate in 1:3 (molar ratio) helped in partial substitution. Molecular docking was performed to see the interaction of the designed compounds with two bacterial and one viral (neuraminidase) receptor. Some of the derivatives showed good interaction with the active site of bacterial and neuraminidase enzymes through hydrogen, hydrophobic and pi-pi interactions, and could inhibit the activity of the selected enzymes.
    Matched MeSH terms: Molecular Docking Simulation
  3. In silico study of carvone derivatives as potential neuraminidase inhibitors
    Jusoh N, Zainal H, Abdul Hamid AA, Bunnori NM, Abd Halim KB, Abd Hamid S
    J Mol Model, 2018 Mar 15;24(4):93.
    PMID: 29546582 DOI: 10.1007/s00894-018-3619-6
    Recent outbreaks of highly pathogenic influenza strains have highlighted the need to develop new anti-influenza drugs. Here, we report an in silico study of carvone derivatives to analyze their binding modes with neuraminidase (NA) active sites. Two proposed carvone analogues, CV(A) and CV(B), with 36 designed ligands were predicted to inhibit NA (PDB ID: 3TI6) using molecular docking. The design is based on structural resemblance with the commercial inhibitor, oseltamivir (OTV), ligand polarity, and amino acid residues in the NA active sites. Docking simulations revealed that ligand A18 has the lowest energy binding (∆Gbind) value of -8.30 kcal mol-1, comparable to OTV with ∆Gbind of -8.72 kcal mol-1. A18 formed seven hydrogen bonds (H-bonds) at residues Arg292, Arg371, Asp151, Trp178, Glu227, and Tyr406, while eight H-bonds were formed by OTV with amino acids Arg118, Arg292, Arg371, Glu119, Asp151, and Arg152. Molecular dynamics (MD) simulation was conducted to compare the stability between ligand A18 and OTV with NA. Our simulation study showed that the A18-NA complex is as stable as the OTV-NA complex during the MD simulation of 50 ns through the analysis of RMSD, RMSF, total energy, hydrogen bonding, and MM/PBSA free energy calculations.
    Matched MeSH terms: Molecular Docking Simulation
  4. Fulltext Multipotent Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease: Synthesis, Biological Analysis and Molecular Docking Study of Benzimidazole-Based Thiazole Derivatives
    Hussain R, Ullah H, Rahim F, Sarfraz M, Taha M, Iqbal R, et al.
    Molecules, 2022 Sep 18;27(18).
    PMID: 36144820 DOI: 10.3390/molecules27186087
    Twenty-four analogues of benzimidazole-based thiazoles (1-24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30 µM (for AChE) and 0.20 ± 0.050 µM to 14.20 ± 0.10 µM (for BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.
    Matched MeSH terms: Molecular Docking Simulation
  5. β Mangostin suppress LPS-induced inflammatory response in RAW 264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo
    Syam S, Bustamam A, Abdullah R, Sukari MA, Hashim NM, Mohan S, et al.
    J Ethnopharmacol, 2014 Apr 28;153(2):435-45.
    PMID: 24607509 DOI: 10.1016/j.jep.2014.02.051
    The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.
    Matched MeSH terms: Molecular Docking Simulation
  6. Mononuclear dioxomolybdenum(VI) thiosemicarbazonato complexes: Synthesis, characterization, structural illustration, in vitro DNA binding, cleavage, and antitumor properties
    Hussein MA, Guan TS, Haque RA, Khadeer Ahamed MB, Abdul Majid AM
    Spectrochim Acta A Mol Biomol Spectrosc, 2015 Feb 05;136 Pt C:1335-48.
    PMID: 25456676 DOI: 10.1016/j.saa.2014.10.021
    Four dioxomolybdenum(VI) complexes were synthesized by reacting [MoO2(acac)2] with N-ethyl-2-(5-bromo-2-hydroxybenzylidene) hydrazinecarbothioamide (1), N-ethyl-2-(5-allyl-3-methoxy-2-hydroxybenzylidene) hydrazinecarbothioamide (2), N-methyl-2-(3-tert-butyl-2-hydroxybenzylidene) hydrazinecarbothioamide (3), and N-ethyl-2-(3-methyl-2-hydroxybenzylidene) hydrazinecarbothioamide (4). The molecular structures of 1, 2, and all the synthesized complexes were determined using single crystal X-ray crystallography. The binding properties of the ligand and complexes with calf thymus DNA (CT-DNA) were investigated via UV, fluorescence titrations, and viscosity measurement. Gel electrophoresis revealed that all the complexes cleave pBR 322 plasmid DNA. The cytotoxicity of the complexes were studied against the HCT 116 human colorectal cell line. All the complexes exhibited more pronounced activity than the standard reference drug 5-fluorouracil (IC50 7.3μM). These studies show that dioxomolybdenum(VI) complexes could be potentially useful in chemotherapy.
    Matched MeSH terms: Molecular Docking Simulation
  7. Fulltext Conjugation of benzylvanillin and benzimidazole structure improves DNA binding with enhanced antileukemic properties
    Al-Mudaris ZA, Majid AS, Ji D, Al-Mudarris BA, Chen SH, Liang PH, et al.
    PLoS One, 2013;8(11):e80983.
    PMID: 24260527 DOI: 10.1371/journal.pone.0080983
    Benzyl-o-vanillin and benzimidazole nucleus serve as important pharmacophore in drug discovery. The benzyl vanillin (2-(benzyloxy)-3-methoxybenzaldehyde) compound shows anti-proliferative activity in HL60 leukemia cancer cells and can effect cell cycle progression at G2/M phase. Its apoptosis activity was due to disruption of mitochondrial functioning. In this study, we have studied a series of compounds consisting of benzyl vanillin and benzimidazole structures. We hypothesize that by fusing these two structures we can produce compounds that have better anticancer activity with improved specificity particularly towards the leukemia cell line. Here we explored the anticancer activity of three compounds namely 2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2MP, N-1-(2-benzyloxy-3-methoxybenzyl)-2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2XP, and (R) and (S)-1-(2-benzyloxy-3-methoxyphenyl)-2, 2, 2-trichloroethyl benzenesulfonate, 3BS and compared their activity to 2-benzyloxy-3-methoxybenzaldehyde, (Bn1), the parent compound. 2XP and 3BS induces cell death of U937 leukemic cell line through DNA fragmentation that lead to the intrinsic caspase 9 activation. DNA binding study primarily by the equilibrium binding titration assay followed by the Viscosity study reveal the DNA binding through groove region with intrinsic binding constant 7.39 µM/bp and 6.86 µM/bp for 3BS and 2XP respectively. 2XP and 3BS showed strong DNA binding activity by the UV titration method with the computational drug modeling showed that both 2XP and 3BS failed to form any electrostatic linkages except via hydrophobic interaction through the minor groove region of the nucleic acid. The benzylvanillin alone (Bn1) has weak anticancer activity even after it was combined with the benzimidazole (2MP), but after addition of another benzylvanillin structure (2XP), stronger activity was observed. Also, the combination of benzylvanillin with benzenesulfonate (3BS) significantly improved the anticancer activity of Bn1. The present study provides a new insight of benzyl vanillin derivatives as potential anti-leukemic agent.
    Matched MeSH terms: Molecular Docking Simulation
  8. Fulltext In Silico Screening of Aptamers Configuration against Hepatitis B Surface Antigen
    Sabri MZ, Abdul Hamid AA, Sayed Hitam SM, Abdul Rahim MZ
    Adv Bioinformatics, 2019;2019:6912914.
    PMID: 31346332 DOI: 10.1155/2019/6912914
    Aptamer has been long studied as a substitute of antibodies for many purposes. However, due to the exceeded length of the aptamers obtained in vitro, difficulties arise in its manipulation during its molecular conjugation on the matrix surfaces. Current study focuses on computational improvement for aptamers screening of hepatitis B surface antigen (HBsAg) through optimization of the length sequences obtained from SELEX. Three original aptamers with affinity against HBsAg were truncated into five short hairpin structured aptamers and their affinity against HBsAg was thoroughly studied by molecular docking, molecular dynamics (MD) simulation, and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method. The result shows that truncated aptamers binding on HBsAg "a" determinant region are stabilized by the dynamic H-bond formation between the active binding residues and nucleotides. Amino acids residues with the highest hydrogen bonds hydrogen bond interactions with all five aptamers were determined as the active binding residues and further characterized. The computational prediction of complexes binding will include validations through experimental assays in future studies. Current study will improve the current in vitro aptamers by minimizing the aptamer length for its easy manipulation.
    Matched MeSH terms: Molecular Docking Simulation
  9. 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
  10. Novel furan-containing peptide-based inhibitors of protein arginine deiminase type IV (PAD4)
    Teo CY, Tejo BA, Leow ATC, Salleh AB, Abdul Rahman MB
    Chem Biol Drug Des, 2017 Dec;90(6):1134-1146.
    PMID: 28581157 DOI: 10.1111/cbdd.13033
    Protein arginine deiminase type IV (PAD4) is responsible for the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullinated protein is the autoantigen in rheumatoid arthritis, and therefore, PAD4 is currently a promising therapeutic target for the disease. Recently, we reported the importance of the furan ring in the structure of PAD4 inhibitors. In this study, the furan ring was incorporated into peptides to act as the "warhead" of the inhibitors for PAD4. IC50 studies showed that the furan-containing peptide-based inhibitors were able to inhibit PAD4 to a better extent than the furan-containing small molecules that were previously reported. The best peptide-based inhibitor inhibited PAD4 reversibly and competitively with an IC50 value of 243.2 ± 2.4 μm. NMR spectroscopy and NMR-restrained molecular dynamic simulations revealed that the peptide-based inhibitor had a random structure. Molecular docking studies showed that the peptide-based inhibitor entered the binding site and interacted with the essential amino acids involved in the catalytic activity. The peptide-based inhibitor could be further developed into a therapeutic drug for rheumatoid arthritis.
    Matched MeSH terms: Molecular Docking Simulation
  11. Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles
    Yeong KY, Tan SC, Mai CW, Leong CO, Chung FF, Lee YK, et al.
    Chem Biol Drug Des, 2018 01;91(1):213-219.
    PMID: 28719017 DOI: 10.1111/cbdd.13072
    Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activities. We showed that modification on benzimidazoles may alter their selectivity toward sirtuin or PARP-1 enzymes. This offers an opportunity for further discovery and development of new promising sirtuin inhibitors. Molecular docking studies were carried out to aid the rationalization of these observations. Preliminary antiproliferative studies of selected compounds against nasopharyngeal cancer cells also showed relatively promising results.
    Matched MeSH terms: Molecular Docking Simulation
  12. Fulltext Fragment-based in silico design of SARS-CoV-2 main protease inhibitors
    Ahmad S, Usman Mirza M, Yean Kee L, Nazir M, Abdul Rahman N, Trant JF, et al.
    Chem Biol Drug Des, 2021 Oct;98(4):604-619.
    PMID: 34148292 DOI: 10.1111/cbdd.13914
    3CLpro is essential for SARS-CoV-2 replication and infection; its inhibition using small molecules is a potential therapeutic strategy. In this study, a comprehensive crystallography-guided fragment-based drug discovery approach was employed to design new inhibitors for SARS-CoV-2 3CLpro. All small molecules co-crystallized with SARS-CoV-2 3CLpro with structures deposited in the Protein Data Bank were used as inputs. Fragments sitting in the binding pocket (87) were grouped into eight geographical types. They were interactively coupled using various synthetically reasonable linkers to generate larger molecules with divalent binding modes taking advantage of two different fragments' interactions. In total, 1,251 compounds were proposed, and 7,158 stereoisomers were screened using Glide (standard precision and extra precision), AutoDock Vina, and Prime MMGBSA. The top 22 hits having conformations approaching the linear combination of their constituent fragments were selected for MD simulation on Desmond. MD simulation suggested 15 of these did adopt conformations very close to their constituent pieces with far higher binding affinity than either constituent domain alone. These structures could provide a starting point for the further design of SARS-CoV-2 3CLpro inhibitors with improved binding, and structures are provided.
    Matched MeSH terms: Molecular Docking Simulation
  13. Benzimidazole derivatives as new α-glucosidase inhibitors and in silico studies
    Zawawi NK, Taha M, Ahmat N, Wadood A, Ismail NH, Rahim F, et al.
    Bioorg Chem, 2016 Feb;64:29-36.
    PMID: 26637946 DOI: 10.1016/j.bioorg.2015.11.006
    Newly synthesized benzimidazole hydrazone derivatives 1-26 were evaluated for their α-glucosidase inhibitory activity. Compounds 1-26 exhibited varying degrees of yeast α-glucosidase inhibitory activity with IC50 values between 8.40 ± 0.76 and 179.71 ± 1.11 μM when compared with standard acarbose. In this assay, seven compounds that showed highest inhibitory effects than the rest of benzimidazole series were identified. All the synthesized compounds were characterized by different spectroscopic methods adequately. We further evaluated the interaction of the active compounds with enzyme with the help of docking studies.
    Matched MeSH terms: Molecular Docking Simulation
  14. 3-Benzyl(phenethyl)-2-thioxobenzo[g]quinazolines as a new class of potent α-glucosidase inhibitors: synthesis and molecular docking study
    Al-Salahi R, Ahmad R, Anouar E, Iwana Nor Azman NI, Marzouk M, Abuelizz HA
    Future Med Chem, 2018 08 01;10(16):1889-1905.
    PMID: 29882426 DOI: 10.4155/fmc-2018-0141
    AIM: Using a simple modification on a previously reported synthetic route, 3-benzyl(phenethyl)-2-thioxobenzo[g]quinazolin-4(3H)-ones (1 and 2) were synthesized with high yields. Further transformation of 1 and 2 produced derivatives 3-26, which were structurally characterized based on NMR and MS data, and their in vitro α-glucosidase inhibitory activity was evaluated using Baker's yeast α-glucosidase enzyme.

    RESULTS: Compounds 2, 4, 8, 12 and 20 exhibited the highest activity (IC50 = 69.20, 59.60, 49.40, 50.20 and 83.20 μM, respectively) compared with the standard acarbose (IC50 = 143.54 μM).

    CONCLUSION: A new class of potent α-glucosidase inhibitors was identified, and the molecular docking predicted plausible binding interaction of the targets in the binding pocket of α-glucosidase and rationalized the structure-activity relationship (SARs) of the target compounds.

    Matched MeSH terms: Molecular Docking Simulation*
  15. tLyp-1: A peptide suitable to target NRP-1 receptor
    Larue L, Kenzhebayeva B, Al-Thiabat MG, Jouan-Hureaux V, Mohd-Gazzali A, Wahab HA, et al.
    Bioorg Chem, 2023 Jan;130:106200.
    PMID: 36332316 DOI: 10.1016/j.bioorg.2022.106200
    Targeting vascular endothelial growth factor receptor (VEFGR) and its co-receptor neuropilin-1 (NRP-1) is an interesting vascular strategy. tLyp-1 is a tumor-homing and penetrating peptide of 7 amino acids (CGNKRTR). It is a truncated form of Lyp-1 (CGNKRTRGC), which is known to target NRP-1 receptor, with high affinity and specificity. It is mediated by endocytosis via C-end rule (CendR) internalization pathway. The aim of this study is to evaluate the importance of each amino acid in the tLyp-1 sequence through alanine-scanning (Ala-scan) technique, during which each of the amino acid in the sequence was systematically replaced by alanine to produce 7 different analogues. In silico approach through molecular docking and molecular dynamics are employed to understand the interaction between the peptide and its analogues with the NRP-1 receptor, followed by in vitro ligand binding assay study. The C-terminal Arg is crucial in the interaction of tLyp-1 with NRP-1 receptor. Substituting this residue dramatically reduces the affinity of this peptide which is clearly seen in this study. Lys-4 is also important in the interaction, which is confirmed via the in vitro study and the MM-PBSA analysis. The finding in this study supports the CendR, in which the presence of R/K-XX-R/K motif is essential in the binding of a ligand with NRP-1 receptor. This presented work will serve as a guide in the future work pertaining the development of active targeting agent towards NRP-1 receptor.
    Matched MeSH terms: Molecular Docking Simulation
  16. Polypharmacology of some medicinal plant metabolites against SARS-CoV-2 and host targets: Molecular dynamics evaluation of NSP9 RNA binding protein
    Bandyopadhyay S, Abiodun OA, Ogboo BC, Kola-Mustapha AT, Attah EI, Edemhanria L, et al.
    J Biomol Struct Dyn, 2022;40(22):11467-11483.
    PMID: 34370622 DOI: 10.1080/07391102.2021.1959401
    Medicinal plants as rich sources of bioactive compounds are now being explored for drug development against COVID-19. 19 medicinal plants known to exhibit antiviral and anti-inflammatory effects were manually curated, procuring a library of 521 metabolites; this was virtually screened against NSP9, including some other viral and host targets and were evaluated for polypharmacological indications. Leads were identified via rigorous scoring thresholds and ADMET filtering. MM-GBSA calculation was deployed to select NSP9-Lead complexes and the complexes were evaluated for their stability and protein-ligand communication via MD simulation. We identified 5 phytochemical leads for NSP9, 23 for Furin, 18 for ORF3a, and 19 for IL-6. Ochnaflavone and Licoflavone B, obtained from Lonicera japonica (Japanese Honeysuckle) and Glycyrrhiza glabra (Licorice), respectively, were identified to have the highest potential polypharmacological properties for the aforementioned targets and may act on multiple pathways simultaneously to inhibit viral entry, replication, and disease progression. Additionally, MD simulation supports the robust stability of Ochnaflavone and Licoflavone B against NSP9 at the active sites via hydrophobic interactions, H-bonding, and H-bonding facilitated by water. This study promotes the initiation of further experimental analysis of natural product-based anti-COVID-19 therapeutics.
    Matched MeSH terms: Molecular Docking Simulation
  17. Fulltext Combining In Silico and In Vitro Studies to Evaluate the Acetylcholinesterase Inhibitory Profile of Different Accessions and the Biomarker Triterpenes of Centella asiatica
    Jusril NA, Muhamad Juhari ANN, Abu Bakar SI, Md Saad WM, Adenan MI
    Molecules, 2020 Jul 24;25(15).
    PMID: 32721993 DOI: 10.3390/molecules25153353
    Alzheimer's disease (AD) is a neurodegenerative disease and the most cause of dementia in elderly adults. Acetylcholinesterase (AChE) is an important beneficial target for AD to control cholinergic signaling deficit. Centella asiatica (CA) has proven to be rich with active ingredients for memory enhancement. In the present study, the chemical profiling of three accession extracts of CA namely SECA-K017, SECA-K018, and, SECA-K019 were performed using high-performance liquid chromatography (HPLC). Four biomarker triterpene compounds were detected in all CA accessions. Quantitative analysis reveals that madecassoside was the highest triterpene in all the CA accessions. The biomarker compounds and the ethanolic extracts of three accessions were investigated for their acetylcholinesterase (AChE) inhibitory activity using Ellman's spectrophotometer method. The inhibitory activity of the triterpenes and accession extracts was compared with the standard AChE inhibitor eserine. The results from the in vitro study showed that the triterpene compounds exhibited an AChE inhibitory activity with the half-maximal inhibitory concentration (IC50) values between 15.05 ± 0.05 and 59.13 ± 0.18 µg/mL. Asiatic acid was found to possess strong AChE inhibitory activity followed by madecassic acid. Among the CA accession extracts, SECA-K017 and SECA-K018 demonstrated a moderate AChE inhibitory activity with an IC50 value of 481.5 ± 0.13 and 763.5 ± 0.16 µg/mL, respectively from the in silico docking studies, it is observed that asiatic acid and madecassic acid showed very good interactions with the active sites and fulfilled docking parameters against AChE. The present study suggested that asiatic acid and madecassic acid in the CA accessions could be responsible for the AChE inhibitory action and could be used as markers to guide further studies on CA as potential natural products for the treatment of AD.
    Matched MeSH terms: Molecular Docking Simulation
  18. Synthesis and molecular modelling studies of phenyl linked oxadiazole-phenylhydrazone hybrids as potent antileishmanial agents
    Taha M, Ismail NH, Imran S, Anouar EH, Selvaraj M, Jamil W, et al.
    Eur J Med Chem, 2017 Jan 27;126:1021-1033.
    PMID: 28012342 DOI: 10.1016/j.ejmech.2016.12.019
    Molecular hybridization yielded phenyl linked oxadiazole-benzohydrazones hybrids 6-35 and were evaluated for their antileishmanial potentials. Compound 10, a 3,4-dihydroxy analog with IC50 value of 0.95 ± 0.01 μM, was found to be the most potent antileishmanial agent (7 times more active) than the standard drug pentamidine (IC50 = 7.02 ± 0.09 μM). The current series 6-35 conceded in the identification of thirteen (13) potent antileishmanial compounds with the IC50 values ranging between 0.95 ± 0.01-78.6 ± 1.78 μM. Molecular docking analysis against pteridine reductase (PTR1) were also performed to probe the mode of action. Selectivity index showed that compounds with higher number of hydroxyl groups have low selectivity index. Theoretical stereochemical assignment was also done for certain derivatives by using density functional calculations.
    Matched MeSH terms: Molecular Docking Simulation*
  19. Fulltext Molecular docking and dynamics simulation studies uncover the host-pathogen protein-protein interactions in Penaeus vannamei and Vibrio parahaemolyticus
    Rosilan NF, Jamali MAM, Sufira SA, Waiho K, Fazhan H, Ismail N, et al.
    PLoS One, 2024;19(1):e0297759.
    PMID: 38266027 DOI: 10.1371/journal.pone.0297759
    Shrimp aquaculture contributes significantly to global economic growth, and the whiteleg shrimp, Penaeus vannamei, is a leading species in this industry. However, Vibrio parahaemolyticus infection poses a major challenge in ensuring the success of P. vannamei aquaculture. Despite its significance in this industry, the biological knowledge of its pathogenesis remains unclear. Hence, this study was conducted to identify the interaction sites and binding affinity between several immune-related proteins of P. vannamei with V. parahaemolyticus proteins associated with virulence factors. Potential interaction sites and the binding affinity between host and pathogen proteins were identified using molecular docking and dynamics (MD) simulation. The P. vannamei-V. parahaemolyticus protein-protein interaction of Complex 1 (Ferritin-HrpE/YscL family type III secretion apparatus protein), Complex 2 (Protein kinase domain-containing protein-Chemotaxis CheY protein), and Complex 3 (GPCR-Chemotaxis CheY protein) was found to interact with -4319.76, -5271.39, and -4725.57 of the docked score and the formation of intermolecular bonds at several interacting residues. The docked scores of Complex 1, Complex 2, and Complex 3 were validated using MD simulation analysis, which revealed these complexes greatly contribute to the interactions between P. vannamei and V. parahaemolyticus proteins, with binding free energies of -22.50 kJ/mol, -30.20 kJ/mol, and -26.27 kJ/mol, respectively. This finding illustrates the capability of computational approaches to search for molecular binding sites between host and pathogen, which could increase the knowledge of Vibrio spp. infection on shrimps, which then can be used to assist in the development of effective treatment.
    Matched MeSH terms: Molecular Docking Simulation
  20. 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
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