Displaying publications 1 - 20 of 265 in total

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  1. A Razak SA, Mohd Gazzali A, Fisol FA, M Abdulbaqi I, Parumasivam T, Mohtar N, et al.
    Cancers (Basel), 2021 Jan 22;13(3).
    PMID: 33499040 DOI: 10.3390/cancers13030400
    Docetaxel (DCX) is a highly effective chemotherapeutic drug used in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). The drug is known to have low oral bioavailability due to its low aqueous solubility, poor membrane permeability and susceptibility to hepatic first-pass metabolism. To mitigate these problems, DCX is administered via the intravenous route. Currently, DCX is commercially available as a single vial that contains polysorbate 80 and ethanol to solubilize the poorly soluble drug. However, this formulation causes short- and long-term side effects, including hypersensitivity, febrile neutropenia, fatigue, fluid retention, and peripheral neuropathy. DCX is also a substrate to the drug efflux pump P-glycoprotein (P-gp) that would reduce its concentration within the vicinity of the cells and lead to the development of drug resistance. Hence, the incorporation of DCX into various nanocarrier systems has garnered a significant amount of attention in recent years to overcome these drawbacks. The surfaces of these drug-delivery systems indeed can be functionalized by modification with different ligands for smart targeting towards cancerous cells. This article provides an overview of the latest nanotechnological approaches and the delivery systems that were developed for passive and active delivery of DCX via different routes of administration for the treatment of lung cancer.
    Matched MeSH terms: Ligands
  2. 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: Ligands
  3. Frimayanti N, Zain SM, Lee VS, Wahab HA, Yusof R, Abd Rahman N
    In Silico Biol. (Gedrukt), 2011;11(1-2):29-37.
    PMID: 22475750 DOI: 10.3233/ISB-2012-0442
    Publication year=2011-2012
    Matched MeSH terms: Ligands
  4. Lee SK, Tan KW, Ng SW, Ooi KK, Ang KP, Abdah MA
    PMID: 24231745 DOI: 10.1016/j.saa.2013.10.084
    A cationic Schiff base ligand, TSB (L) and its Zn (II) complex (1) were synthesized and characterized by using CHN, (1)H-NMR, FT-IR, UV, LC-MS, and X-ray methods. Their ability to inhibit topoisomerase I, DNA cleavage activities, and cytotoxicity were studied. X-ray diffraction study shows that the mononuclear complex 1 is four coordinated with distorted tetrahedral geometry. The singly deprotonated Schiff base ligand L acts as a bidentate ON-donor ligand. Complexation of L increases the inhibitory strength on topoisomerase I activity. Complex 1 could fully inhibit topoisomerase I activity at 250 μM, while L did not show any inhibitory effect on topoisomerase I activity. In addition, L and complex 1 could cleave pBR322 DNA in a concentration and time dependent profile. Surprisingly, L has better DNA cleavage activity than complex 1. The cleavage of DNA by complex 1 is altered in the presence of hydrogen peroxide. Furthermore, L and complex 1 are mildly cytotoxic towards human ovarian cancer A2780 and hepatocellular carcinoma HepG2.
    Matched MeSH terms: Ligands
  5. Ahmed A, Saeed F, Salim N, Abdo A
    J Cheminform, 2014;6:19.
    PMID: 24883114 DOI: 10.1186/1758-2946-6-19
    BACKGROUND: It is known that any individual similarity measure will not always give the best recall of active molecule structure for all types of activity classes. Recently, the effectiveness of ligand-based virtual screening approaches can be enhanced by using data fusion. Data fusion can be implemented using two different approaches: group fusion and similarity fusion. Similarity fusion involves searching using multiple similarity measures. The similarity scores, or ranking, for each similarity measure are combined to obtain the final ranking of the compounds in the database.

    RESULTS: The Condorcet fusion method was examined. This approach combines the outputs of similarity searches from eleven association and distance similarity coefficients, and then the winner measure for each class of molecules, based on Condorcet fusion, was chosen to be the best method of searching. The recall of retrieved active molecules at top 5% and significant test are used to evaluate our proposed method. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints.

    CONCLUSIONS: Simulated virtual screening experiments with the standard two data sets show that the use of Condorcet fusion provides a very simple way of improving the ligand-based virtual screening, especially when the active molecules being sought have a lowest degree of structural heterogeneity. However, the effectiveness of the Condorcet fusion was increased slightly when structural sets of high diversity activities were being sought.

    Matched MeSH terms: Ligands
  6. Mohammad Hood MH, Tengku Abdul Hamid TH, Abdul Wahab RA, Huyop FZ, Kaya Y, Abdul Hamid AAA
    J Biomol Struct Dyn, 2023 Apr;41(7):2831-2847.
    PMID: 35174777 DOI: 10.1080/07391102.2022.2039772
    Efficacy of a β-1,4-glucosidase from Trichoderma harzianum T12 (ThBglT12) in disrupting the cell wall of the phytopathogenic fungus M. phaseolina (Macrophomina phaseolina) was studied, as the underlying molecular mechanisms of cell wall recognition remains elusive. In this study, the binding location identified by a consensus of residues predicted by COACH tool, blind docking, and multiple sequence alignment revealed that molecular recognition by ThBglT12 occurred through interactions between the α-1,3-glucan, β-1,3-glucan, β-1,3/1,4-glucan, and chitin components of M. phaseolina, with corresponding binding energies of -7.4, -7.6, -7.5 and -7.8 kcal/mol. The residue consensus verified the participation of Glu172, Tyr304, Trp345, Glu373, Glu430, and Trp431 in the active site pocket of ThBglT12 to bind the ligands, of which Trp345 was the common interacting residue. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), total energy, and minimum distance calculation from molecular dynamics (MD) simulation further confirmed the stability and the closeness of the binding ligands into the ThBglT12 active site pocket. The h-bond occupancy by Glu373 and Trp431 instated the role of the nucleophile for substrate recognition and specificity, crucial for cleaving the β-1,4 linkage. Further investigation showed that the proximity of Glu373 to the anomeric carbon of β-1,3/1,4-glucan (3.5 Å) and chitin (5.5 Å) indicates the nucleophiles' readiness to form enzyme-substrate intermediates. Plus, the neighboring water molecule appeared to be correctly positioned and oriented towards the anomeric carbon to hydrolyze the β-1,3/1,4-glucan and chitin, in less than 4.0 Å. In a nutshell, the study verified that the ThBglT12 is a good alternative fungicide to inhibit the growth of M. phaseolina.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Ligands
  7. Yip FW, Yang Farina, Ibrahim Baba, Abdul Hamid Othman
    Organostannum(IV) complexes derived from dicarboxylic acids have been successfully synthesised from triphenylstannum(IV) hydroxide (Ph3SnOH). The complexes were obtained by refluxing Ph3SnOH and the respective dicarboxylic acids (malonic, succinic, glutaric and adipic acids) using a Dean and Stark apparatus in the appropriate solvent. The free ligands and complexes were characterised by C, Hand Sn elemental analysis and spectroscopic methods such as infrared and nuclear magnetic resonance (1H, 13C NMR). Structure determination of triphenylstannum(IV) succinate, 2, showed that each dicarboxylate anion was bonded monodentatically to two triphenylstannum(IV) moieties. The geometry surrounding each stannum atom is close to a tetrahedron. Spectroscopic data obtained for all complexes were found to be similar and thus it may be concluded that all complexes have the same structure as 2.
    Matched MeSH terms: Ligands
  8. Arunagiri C, Subashini A, Saranya M, Thomas Muthiah P, Thanigaimani K, Abdul Razak I
    PMID: 25084236 DOI: 10.1016/j.saa.2014.07.016
    The molecular structure of a new Schiff base, 2-[4-hydroxy benzylidene]-amino naphthalene (HBAN) has been examined by HF and B3LYP/6-311++G(d,p) calculations. The X-ray structure was determined in order to establish the conformation of the molecule. The compound, C17H13NO, crystallizes in the orthorhombic, P212121 space group with the cell dimension, a=6.2867(2), b=10.2108(3), c=19.2950(6) Å, α=β=γ=90° and z=4. The asymmetric unit contains a molecule of a Schiff base. A strong intermolecular O-H⋯N and a weak C-H⋯O hydrogen bonds stabilized the crystal structure. The vibrational spectra of HBAN have been calculated using density functional theoretical computation and compared with the experimental. The study is extended to the HOMO-LUMO analysis to calculate the energy gap (Δ), Ionization potential (I), Electron Affinity (A), Global Hardness (η), Chemical Potential (μ) and Global Electrophilicity (w). The calculated HOMO and LUMO energy reveals that the charge transfer occurs within the molecule.
    Matched MeSH terms: Ligands
  9. Hajrezaie M, Golbabapour S, Hassandarvish P, Gwaram NS, A Hadi AH, Mohd Ali H, et al.
    PLoS One, 2012;7(12):e51537.
    PMID: 23251568 DOI: 10.1371/journal.pone.0051537
    BACKGROUND: Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II) complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats.

    METHODOLOGY/PRINCIPAL FINDINGS: Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v). Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20). Groups 4-7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20), respectively. Tween 20 (10% v/v) was given orally to group 1 and absolute ethanol was given orally to groups 2-7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE(2)) activities and a decrease in malondialdehyde (MDA) level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4-7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4-7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound.

    CONCLUSIONS/SIGNIFICANCE: The gastroprotective effect of the Copper (II) complex may possibly be due to preservation of gastric wall mucus; increase in PGE(2) synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein.

    Matched MeSH terms: Ligands
  10. Rahman ML, Wong ZJ, Sarjadi MS, Joseph CG, Arshad SE, Musta B, et al.
    Polymers (Basel), 2021 May 06;13(9).
    PMID: 34066308 DOI: 10.3390/polym13091486
    Toxic metals in the industrial wastewaters have been liable for drastic pollution hence a powerful and economical treatment technology is needed for water purification. For this reason, some pure cellulosic materials were derived from waste fiber to obtain an economical adsorbent for wastewater treatment. Conversion of cellulose into grafting materials such as poly(methyl acrylate)-grafted cellulose was performed by free radical grafting process. Consequently, poly(hydroxamic acid) ligand was produced from the grafted cellulose. The intermediate products and poly(hydroxamic acid) ligand were analyzed by FT-IR, FE-SEM, TEM, EDX, and XPS spectroscopy. The adsorption capacity (qe) of some toxic metals ions by the polymer ligand was found to be excellent, e.g., copper capacity (qe) was 346.7 mg·g-1 at pH 6. On the other hand, several metal ions such as cobalt chromium and nickel also demonstrated noteworthy sorption capacity at pH 6. The adsorption mechanism obeyed the pseudo second-order rate kinetic model due to the satisfactory correlated experimental sorption values (qe). Langmuir model isotherm study showed the significant correlation coefficient with all metal ions (R2 > 0.99), indicating that the single or monolayer adsorption was the dominant mode on the surface of the adsorbent. This polymer ligand showed good properties on reusability. The result shows that the adsorbent may be recycled for 6 cycles without any dropping of starting sorption capabilities. This polymeric ligand showed outstanding toxic metals removal magnitude, up to 90-99% of toxic metal ions can be removed from industrial wastewater.
    Matched MeSH terms: Ligands
  11. 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: Ligands
  12. Camacho F, Moreno E, Garcia-Alles LF, Chinea Santiago G, Gilleron M, Vasquez A, et al.
    Front Immunol, 2020;11:566710.
    PMID: 33162982 DOI: 10.3389/fimmu.2020.566710
    Lipids, glycolipids and lipopeptides derived from Mycobacterium tuberculosis (Mtb) are presented to T cells by monomorphic molecules known as CD1. This is the case of the Mtb-specific sulfoglycolipid Ac2SGL, which is presented by CD1b molecules and is recognized by T cells found in tuberculosis (TB) patients and in individuals with latent infections. Our group, using filamentous phage display technology, obtained two specific ligands against the CD1b-Ac2SGL complex: (i) a single chain T cell receptor (scTCR) from a human T cell clone recognizing the CD1b-AcSGL complex; and (ii) a light chain domain antibody (dAbκ11). Both ligands showed lower reactivity to a synthetic analog of Ac2SGL (SGL12), having a shorter acyl chain as compared to the natural antigen. Here we put forward the hypothesis that the CD1b endogenous spacer lipid (EnSpacer) plays an important role in the recognition of the CD1b-Ac2SGL complex by specific T cells. To support this hypothesis we combined: (a) molecular binding assays for both the scTCR and the dAbκ11 antibody domain against a small panel of synthetic Ac2SGL analogs having different acyl chains, (b) molecular modeling of the CD1b-Ac2SGL/EnSpacer complex, and (c) modeling of the interactions of this complex with the scTCR. Our results contribute to understand the mechanisms of lipid presentation by CD1b molecules and their interactions with T-cell receptors and other specific ligands, which may help to develop specific tools targeting Mtb infected cells for therapeutic and diagnostic applications.
    Matched MeSH terms: Ligands
  13. Hajeb P, Sloth JJ, Shakibazadeh S, Mahyudin NA, Afsah-Hejri L
    Compr Rev Food Sci Food Saf, 2014 Jul;13(4):457-472.
    PMID: 33412705 DOI: 10.1111/1541-4337.12068
    Toxic elements such as mercury, arsenic, cadmium, and lead, sometimes called heavy metals, can diminish mental and central nervous system function; elicit damage to blood composition as well as the kidneys, lungs, and liver; and reduce energy levels. Food is considered one of the main routes of their entry into the human body. Numerous studies have been performed to examine the effects of common food processing procedures on the levels of toxic elements in food. While some studies have reported negative effects of processing, several have shown that processing practices may have a positive effect on the reduction of toxic elements in foodstuffs. A number of studies have also introduced protocols and suggested chemical agents that reduce the amount of toxic elements in the final food products. In this review, the reported methods employed for the reduction of toxic elements are discussed with particular emphasis on the chemical binding of both the organic and inorganic forms of each element in various foods. The molecular groups and the ligands by which the food products bind with the metals and the types of these reactions are also presented.
    Matched MeSH terms: Ligands
  14. Md Yusof EN, S A Ravoof TB, Tiekink ER, Veerakumarasivam A, Crouse KA, Mohamed Tahir MI, et al.
    Int J Mol Sci, 2015 May 15;16(5):11034-54.
    PMID: 25988384 DOI: 10.3390/ijms160511034
    Two bidentate NS ligands were synthesized by the condensation reaction of S-2-methylbenzyldithiocarbazate (S2MBDTC) with 2-methoxybenzaldehyde (2MB) and 3-methoxybenzaldehyde (3MB). The ligands were reacted separately with acetates of Cu(II), Ni(II) and Zn(II) yielding 1:2 (metal:ligand) complexes. The metal complexes formed were expected to have a general formula of [M(NS)2] where M = Cu2+, Ni2+, and Zn2+. These compounds were characterized by elemental analysis, molar conductivity, magnetic susceptibility and various spectroscopic techniques. The magnetic susceptibility measurements and spectral results supported the predicted coordination geometry in which the Schiff bases behaved as bidentate NS donor ligands coordinating via the azomethine nitrogen and thiolate sulfur. The molecular structures of the isomeric S2M2MBH (1) and S2M3MBH (2) were established by X-ray crystallography to have very similar l-shaped structures. The Schiff bases and their metal complexes were evaluated for their biological activities against estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cell lines. Only the Cu(II) complexes showed marked cytotoxicity against the cancer cell lines. Both Schiff bases and other metal complexes were found to be inactive. In concordance with the cytotoxicity studies, the DNA binding studies indicated that Cu(II) complexes have a strong DNA binding affinity.
    Matched MeSH terms: Ligands*
  15. Ting T, Crouse K, Ahmad H
    Sains Malaysiana, 2015;44:619-628.
    Three novel ruthenium(II) complexes of the general formula [Ru(II)(bpy)2
    L]2+ were synthesized, where L =
    1,10-phenanthroline derivatives of position 2 imidazole having 3,4-didecyloxy-phenyl (ddip), 3,4-ditetradecyloxy-phenyl
    (dtip) and 3,4-dihexadecyloxy-phenyl (dhip). All complexes were characterized by elemental analysis, 1
    H-NMR and ESI-MS.
    Their photophysical properties have also been studied by UV-visible spectroscopy and fluorescence spectroscopy. The
    complexes exhibit Ru(II) metal centered emission at approximately 610 nm in acetonitrile solution at room temperature. DNA
    binding studies were carried out by UV-visible titration, luminescence titration and viscosity studies. The results indicated
    that [Ru(bpy)2
    (ddip)]2+ binds to CT-DNA by partial intercalation mode, while [Ru(bpy)2
    (dtip)]2+ and [Ru(bpy)2
    (dhip)]2+
    bind intercalatively via extended ligands.
    Matched MeSH terms: Ligands
  16. Zaini MS, Liew JYC, Alang Ahmad SA, Mohmad AR, Ahmad Kamarudin M
    ACS Omega, 2020 Dec 08;5(48):30956-30962.
    PMID: 33324803 DOI: 10.1021/acsomega.0c03768
    The existence of surface organic capping ligands on quantum dots (QDs) has limited the potential in QDs emission properties and energy band gap structure alteration as well as the carrier localization. This drawback can be addressed via depositing a thin layer of a semiconductor material on the surface of QDs. Herein, we report on the comparative study for photoluminescent (PL) properties of PbS and PbS/MnS QDs. The carrier localization effect due to the alteration of energy band gap structure and carrier recombination mechanism in the QDs were investigated via PL measurements in a temperature range of 10-300 K with the variation of the excitation power from 10 to 200 mW. For PbS QDs, the gradient of integrated PL intensity (IPL) as a function of excitation power density graph was less than unity. When the MnS shell layer was deposited onto the PbS core, the PL emission exhibited a blue shift, showing dominant carrier recombination. It was also found that the full width half-maximum showed a gradual broadening with the increasing temperature, affirming the electron-phonon interaction.
    Matched MeSH terms: Ligands
  17. Mazlan NS, Ahmad Khairudin NB
    J Biomol Struct Dyn, 2016 Jul;34(7):1486-94.
    PMID: 26261863 DOI: 10.1080/07391102.2015.1081570
    Paenibacillus polymyxa β-glucosidase B (BglB), belongs to a GH family 1, is a monomeric enzyme that acts as an exo-β-glucosidase hydrolysing cellobiose and cellodextrins of higher degree of polymerization using retaining mechanism. A molecular dynamics (MD) simulation was performed at 300 K under periodic boundary condition for 5 ns using the complexes structure obtained from previous docking study, namely BglB-Beta-d-glucose and BglB-Cellobiose. From the root-mean-square deviation analysis, both enzyme complexes were reported to deviate from the initial structure in the early part of the simulation but it was stable afterwards. The root-mean-square fluctuation analysis revealed that the most flexible regions comprised of the residues from 26 to 29, 43 to 53, 272 to 276, 306 to 325 and 364 to 367. The radius of gyration analysis had shown the structure of BglB without substrate became more compact towards the end of the simulation compare to other two complexes. The residues His122 and Trp410 were observed to form stable hydrogen bond with occupancy higher than 10%. In conclusion, the behaviour of BglB enzyme towards the substrate binding was successfully explored via MD simulation approaches.
    Matched MeSH terms: Ligands*
  18. Abdo A, Salim N, Ahmed A
    J Biomol Screen, 2011 Oct;16(9):1081-8.
    PMID: 21862688 DOI: 10.1177/1087057111416658
    Recently, the use of the Bayesian network as an alternative to existing tools for similarity-based virtual screening has received noticeable attention from researchers in the chemoinformatics field. The main aim of the Bayesian network model is to improve the retrieval effectiveness of similarity-based virtual screening. To this end, different models of the Bayesian network have been developed. In our previous works, the retrieval performance of the Bayesian network was observed to improve significantly when multiple reference structures or fragment weightings were used. In this article, the authors enhance the Bayesian inference network (BIN) using the relevance feedback information. In this approach, a few high-ranking structures of unknown activity were filtered from the outputs of BIN, based on a single active reference structure, to form a set of active reference structures. This set of active reference structures was used in two distinct techniques for carrying out such BIN searching: reweighting the fragments in the reference structures and group fusion techniques. Simulated virtual screening experiments with three MDL Drug Data Report data sets showed that the proposed techniques provide simple ways of enhancing the cost-effectiveness of ligand-based virtual screening searches, especially for higher diversity data sets.
    Matched MeSH terms: Ligands
  19. Himmat M, Salim N, Al-Dabbagh MM, Saeed F, Ahmed A
    Molecules, 2016 Apr 13;21(4):476.
    PMID: 27089312 DOI: 10.3390/molecules21040476
    Quantifying the similarity of molecules is considered one of the major tasks in virtual screening. There are many similarity measures that have been proposed for this purpose, some of which have been derived from document and text retrieving areas as most often these similarity methods give good results in document retrieval and can achieve good results in virtual screening. In this work, we propose a similarity measure for ligand-based virtual screening, which has been derived from a text processing similarity measure. It has been adopted to be suitable for virtual screening; we called this proposed measure the Adapted Similarity Measure of Text Processing (ASMTP). For evaluating and testing the proposed ASMTP we conducted several experiments on two different benchmark datasets: the Maximum Unbiased Validation (MUV) and the MDL Drug Data Report (MDDR). The experiments have been conducted by choosing 10 reference structures from each class randomly as queries and evaluate them in the recall of cut-offs at 1% and 5%. The overall obtained results are compared with some similarity methods including the Tanimoto coefficient, which are considered to be the conventional and standard similarity coefficients for fingerprint-based similarity calculations. The achieved results show that the performance of ligand-based virtual screening is better and outperforms the Tanimoto coefficients and other methods.
    Matched MeSH terms: Ligands
  20. Anwar A, Siddiqui R, Raza Shah M, Ahmed Khan N
    J Microbiol Biotechnol, 2019 Jan 28;29(1):171-177.
    PMID: 30415525 DOI: 10.4014/jmb.1805.05028
    Parasitic infections have remained a significant burden on human and animal health. In part, this is due to lack of clinically-approved, novel antimicrobials and a lack of interest by the pharmaceutical industry. An alternative approach is to modify existing clinically-approved drugs for efficient delivery formulations to ensure minimum inhibitory concentration is achieved at the target site. Nanotechnology offers the potential to enhance the therapeutic efficacy of drugs through modification of nanoparticles with ligands. Amphotericin B, nystatin, and fluconazole are clinically available drugs in the treatment of amoebal and fungal infections. These drugs were conjugated with gold nanoparticles. To characterize these gold-conjugated drug, atomic force microscopy, ultraviolet-visible spectrophotometry and Fourier transform infrared spectroscopy were performed. These drugs and their gold nanoconjugates were examined for antimicrobial activity against the protist pathogen, Acanthamoeba castellanii of the T4 genotype. Moreover, host cell cytotoxicity assays were accomplished. Cytotoxicity of these drugs and drug-conjugated gold nanoparticles was also determined by lactate dehydrogenase assay. Gold nanoparticles conjugation resulted in enhanced bioactivity of all three drugs with amphotericin B producing the most significant effects against Acanthamoeba castellanii (p < 0.05). In contrast, bare gold nanoparticles did not exhibit antimicrobial potency. Furthermore, amoebae treated with drugs-conjugated gold nanoparticles showed reduced cytotoxicity against HeLa cells. In this report, we demonstrated the use of nanotechnology to modify existing clinically-approved drugs and enhance their efficacy against pathogenic amoebae. Given the lack of development of novel drugs, this is a viable approach in the treatment of neglected diseases.
    Matched MeSH terms: Ligands
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