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Article ; Online: Protein network analysis to prioritize key genes in amyotrophic lateral sclerosis.

Kumar, Rupesh / Haider, Shazia

IBRO neuroscience reports

2021 Volume 12, Page(s) 25–44

Abstract: Amyotrophic Lateral Sclerosis (ALS) is a fatal disease, progressive nature characterizes by loss of both upper and lower motor neuron functions. One of the major challenge is to understand the mechanism of ALS multifactorial nature. We aimed to explore ... ...

Abstract	Amyotrophic Lateral Sclerosis (ALS) is a fatal disease, progressive nature characterizes by loss of both upper and lower motor neuron functions. One of the major challenge is to understand the mechanism of ALS multifactorial nature. We aimed to explore some key genes related to ALS through bioinformatics methods for its therapeutic intervention. Here, we applied a systems biology approach involving experimentally validated 148 ALS-associated proteins and construct ALS protein-protein interaction network (ALS-PPIN). The network was further statistically analysed and identified bottleneck-hubs. The network is also subjected to identify modules which could have similar functions. The interaction between the modules and bottleneck-hubs provides the functional regulatory role of the ALS mechanism. The ALS-PPIN demonstrated a hierarchical scale-free nature. We identified 17 bottleneck-hubs, in which
Language	English
Publishing date	2021-12-07
Publishing country	Netherlands
Document type	Journal Article
ISSN	2667-2421
ISSN (online)	2667-2421
DOI	10.1016/j.ibneur.2021.12.002
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Article: Computational study of the motor neuron protein KIF5A to identify nsSNPs, bioactive compounds, and its key regulators.

Kumar, Rupesh / Madhavan, Thirumurthy / Ponnusamy, Kalaiarasan / Sohn, Honglae / Haider, Shazia

Frontiers in genetics

2023 Volume 14, Page(s) 1282234

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-11-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2023.1282234
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Article ; Online: Amyotrophic Lateral Sclerosis Risk Genes and Suppressor.

Kumar, Rupesh / Malik, Zubbair / Singh, Manisha / Rachana, R / Mani, Shalini / Ponnusamy, Kalaiarasan / Haider, Shazia

Current gene therapy

2022 Volume 23, Issue 2, Page(s) 148–162

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to death by progressive paralysis and respiratory failure within 2-4 years of onset. About 90-95% of ALS cases are sporadic (sALS), and 5-10% are inherited through family ...

Abstract	Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to death by progressive paralysis and respiratory failure within 2-4 years of onset. About 90-95% of ALS cases are sporadic (sALS), and 5-10% are inherited through family (fALS). Though the mechanisms of the disease are still poorly understood, so far, approximately 40 genes have been reported as ALS causative genes. The mutations in some crucial genes, like SOD1, C9ORF72, FUS, and TDP-43, are majorly associated with ALS, resulting in ROS-associated oxidative stress, excitotoxicity, protein aggregation, altered RNA processing, axonal and vesicular trafficking dysregulation, and mitochondrial dysfunction. Recent studies show that dysfunctional cellular pathways get restored as a result of the repair of a single pathway in ALS. In this review article, our aim is to identify putative targets for therapeutic development and the importance of a single suppressor to reduce multiple symptoms by focusing on important mutations and the phenotypic suppressors of dysfunctional cellular pathways in crucial genes as reported by other studies.
MeSH term(s)	Humans ; Amyotrophic Lateral Sclerosis/genetics ; Neurodegenerative Diseases ; Mutation
Language	English
Publishing date	2022-11-11
Publishing country	United Arab Emirates
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2146187-9
ISSN	1875-5631 ; 1566-5232
ISSN (online)	1875-5631
ISSN	1566-5232
DOI	10.2174/1566523223666221108113330
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Zs.A 5883: Show issues

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Article ; Online: Combinatorial Network of Transcriptional and miRNA Regulation in Colorectal Cancer.

Kumar, Rupesh / Mahmoud, Maged Mostafa / Tashkandi, Hanaa M / Haque, Shafiul / Harakeh, Steve / Ponnusamy, Kalaiarasan / Haider, Shazia

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Colorectal cancer is one of the leading causes of cancer-associated mortality across the worldwide. One of the major challenges in colorectal cancer is the understanding of the regulatory mechanisms of biological molecules. In this study, we aimed to ... ...

Abstract	Colorectal cancer is one of the leading causes of cancer-associated mortality across the worldwide. One of the major challenges in colorectal cancer is the understanding of the regulatory mechanisms of biological molecules. In this study, we aimed to identify novel key molecules in colorectal cancer by using a computational systems biology approach. We constructed the colorectal protein-protein interaction network which followed hierarchical scale-free nature. We identified
MeSH term(s)	Humans ; MicroRNAs/metabolism ; Gene Regulatory Networks ; Gene Expression Regulation ; Transcription Factors/metabolism ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Computational Biology ; Gene Expression Regulation, Neoplastic
Chemical Substances	MicroRNAs ; Transcription Factors ; ErbB Receptors (EC 2.7.10.1) ; MIRN622 microRNA, human
Language	English
Publishing date	2023-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065356
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Article ; Online: A computational biology approach to identify potential protein biomarkers and drug targets for sporadic amyotrophic lateral sclerosis.

Kumar, Rupesh / Malik, Md Zubbair / Thanaraj, Thangavel Alphonse / Bagabir, Sali Abubaker / Haque, Shafiul / Tambuwala, Murtaza / Haider, Shazia

Cellular signalling

2023 Volume 112, Page(s) 110915

Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of upper and lower motor neurons. The sporadic ALS (sALS) is a multigenic disorder and the complex mechanisms underlying its onset are still not fully delineated. ... ...

Abstract	Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of upper and lower motor neurons. The sporadic ALS (sALS) is a multigenic disorder and the complex mechanisms underlying its onset are still not fully delineated. Despite the recent scientific advancements, certain aspects of ALS pathogenic targets need to be yet clarified. The aim of the presented study is to identify potential genetic biomarkers and drug targets for sALS, by analysing gene expression profiles, presented in the publicly available GSE68605 dataset, of motor neurons cells obtained from sALS patients. We used different computational approaches including differential expression analysis, protein network mapping, candidate protein biomarker (CPB) identification, elucidation of the role of functional modules, and molecular docking analysis. The resultant top ten up- and downregulated genes were further used to construct protein-protein interaction network (PPIN). The PPIN analysis resulted in identifying four CPBs (namely RIOK2, AKT1, CTNNB1, and TNF) that commonly overlapped with one another in network parameters (degree, bottleneck and maximum neighbourhood component). The RIOK2 protein emerged as a potential mediator of top five functional modules that are associated with RNA binding, lipoprotein particle receptor binding in pre-ribosome, and interferon, cytokine-mediated signaling pathway. Furthermore, molecular docking analysis revealed that cyclosporine exhibited the highest binding affinity (-8.6 kJ/mol) with RIOK2, and surpassed the FDA-approved ALS drugs, such as riluzole and edaravone. This suggested that cyclosporine may serve as a promising candidate for targeting RIOK2 downregulation observed in sALS patients. In order to validate our computational results, it is suggested that in vitro and in vivo studies may be conducted in future to provide a more detailed understanding of ALS diagnosis, prognosis, and therapeutic intervention.
MeSH term(s)	Humans ; Amyotrophic Lateral Sclerosis/drug therapy ; Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Neurodegenerative Diseases ; Molecular Docking Simulation ; Proteins ; Computational Biology ; Biomarkers ; Cyclosporins/therapeutic use
Chemical Substances	Proteins ; Biomarkers ; Cyclosporins
Language	English
Publishing date	2023-10-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2023.110915
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Article: Synthesis and characterization of Schiff base of nicotinic hydrazide as antibacterial agent along with in vivo wound healing activities and atomic force microscopic study of bacterial cell wall affected by synthesized compound.

Burki, Samiullah / Burki, Zeba Gul / Haider, Shazia / Mehjabeen, - / Ahmed, Ijaz

Pakistan journal of pharmaceutical sciences

2020 Volume 33, Issue 2, Page(s) 675–683

Abstract: The present work reports the synthesis of Schiff base series of nicotinic hydrazide (C-1-C-5) and it's antibacterial and wound healing evaluation. The synthetic molecules were characterized with different spectroscopic techniques and explored for their ... ...

Abstract	The present work reports the synthesis of Schiff base series of nicotinic hydrazide (C-1-C-5) and it's antibacterial and wound healing evaluation. The synthetic molecules were characterized with different spectroscopic techniques and explored for their antibacterial potential. The objective of this work was to explore antimicrobial agent using two types of microorganisms, one Gram-positive (S. aureus ATCC 9144) and one Gram-negative (E. coli ATCC 10536). C-2, C-4 and C-5 potentially inhibit bacterial growth (p<0.001). Atomic force microscopy (AFM) imaging was obtained to get high-resolution images of the effect of treated drugs on the bacterial morphology. The images obtained also revealed the antibacterial effects of potent molecule. The magnified pictures captured under AFM suggest significantly damaged cell surface and disturbed morphology. The compounds were further analyzed for in vivo wound healing potential on mice. The compound C-2, C-4 and C-5 heal the wounds comparatively in less time duration as compared to control group (p<0.001). Compound C-1 and C-3 took more time to heal the wound as compare to compound C-2, C-4 and C-5. The re-epithelialization process of wound in animals group treated with potent compound was highly significant (p<0.001) and faster than control. Results of this study suggest that the compounds C-2, C-4 andC-5 possess pronounced antibacterial and wound healing potential and need to be further evaluated for mechanism of action.
MeSH term(s)	Animals ; Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/pharmacology ; Cell Wall/drug effects ; Cell Wall/physiology ; Escherichia coli/drug effects ; Escherichia coli/physiology ; Mice ; Microbial Sensitivity Tests/methods ; Microscopy, Atomic Force/methods ; Nicotine/analogs & derivatives ; Nicotine/chemical synthesis ; Nicotine/pharmacology ; Schiff Bases/chemical synthesis ; Schiff Bases/pharmacology ; Staphylococcus aureus/drug effects ; Staphylococcus aureus/physiology ; Wound Healing/drug effects ; Wound Healing/physiology
Chemical Substances	Anti-Bacterial Agents ; Schiff Bases ; nicotine hydrazide ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2020-04-10
Publishing country	Pakistan
Document type	Journal Article
ZDB-ID	885131-1
ISSN	1011-601X
ISSN	1011-601X
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Zs.A 6588: Show issues

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Article: New series of hydrazinyl thiazole derivatives of piperidin-4-one: Synthesis, structural elucidation, analgesic activity and comparative structure activity relationship.

Siddiqui, Rubina / Akhtar, Shamim / Haider, Shazia / Saify, Zafar Saied / Akhtar, Mahwish / Shamim, Sana

Pakistan journal of pharmaceutical sciences

2021 Volume 34, Issue 4, Page(s) 1415–1420

Abstract: Seven new hydrazinyl thiazole derivatives of piperidin-4-one (PE3-PE9) have been synthesized by cyclization of intermediate thiosemicarbazone derivative (PE2). Parent molecule (PE1) was synthesized by one pot total synthesis using Mannich condensation ... ...

Abstract	Seven new hydrazinyl thiazole derivatives of piperidin-4-one (PE3-PE9) have been synthesized by cyclization of intermediate thiosemicarbazone derivative (PE2). Parent molecule (PE1) was synthesized by one pot total synthesis using Mannich condensation reaction. Percent yield of most of the compounds found in between 70-85%. Compounds were identified by spectroscopic analysis. In vivo analgesic activity was examined using tail flick method. One-way ANOVA was used to compare the mean latency time of synthesized derivatives with control and standard. Analgesic activity was discussed in terms of structural differences between compounds. Among allthe derivatives thiosemicarbazone derivative showed good analgesic activity (195.24%). Methoxy (-OCH3) and bromo (-Br) containing thiazole derivative also showed good pain reducing property (167.62%, 203%) at a dose of 30mg/kg.
MeSH term(s)	Analgesics/pharmacology ; Animals ; Molecular Structure ; Pain/prevention & control ; Piperidines/chemical synthesis ; Piperidines/chemistry ; Piperidines/pharmacology ; Structure-Activity Relationship ; Thiazoles/chemical synthesis ; Thiazoles/chemistry ; Thiazoles/pharmacology
Chemical Substances	Analgesics ; Piperidines ; Thiazoles
Language	English
Publishing date	2021-11-19
Publishing country	Pakistan
Document type	Journal Article
ZDB-ID	885131-1
ISSN	1011-601X
ISSN	1011-601X
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Article: Comparative study of antibacterial activity between Schiff base nicotinic hydrazide derivative and its silver architected nanoparticles with atomic force microscopic study of bacterial cell wall.

Burki, Zeba Gul / Burki, Samiullah / Haider, Shazia / Ahmed, Ijaz / Mehjabeen, - / Zafar, Saba

Pakistan journal of pharmaceutical sciences

2021 Volume 33, Issue 5, Page(s) 1987–1994

Abstract: The threat of multi-drug resistant bacterial pathogens evokes researchers to synthesized safe and effective chemotherapeutic agents for nano-drug delivery system. In current study, Schiff base of nicotinic hydrazide(NHD) and its silver nanoparticles(NHD- ... ...

Abstract	The threat of multi-drug resistant bacterial pathogens evokes researchers to synthesized safe and effective chemotherapeutic agents for nano-drug delivery system. In current study, Schiff base of nicotinic hydrazide(NHD) and its silver nanoparticles(NHD-AgNPs) were synthesized and characterized. These compounds were investigated for cytotoxicity, antibacterial and AFM activity. The NHD showed LD50 at >1000μg/mL while NHD-AgNPs didn't exhibit toxicity at 1000μg/mL against 3T3 cell line. The NHD showed zone of inhibition against two strains of salmonella enteric (ATCC 14028 and 700408) 45.29±1.66 and 48.01±1.43mm respectively at 160μg/mL (p<0.01) while NHD-AgNPs exhibited 55.87±2.08 and 52.88±1.42 mm respectively at 130μg/mL (p<0.001) in disc diffusion method. NHD showed more than 70% growth inhibition for both strains at 85 and 125μg/ml (p<0.01) respectively, while NHD-AgNPs inhibit 80% and 75% respectively at 75 and 125 μg/ml (p<0.01, p<0.001) against Alamar blue antibacterial assay. For morphological changes in bacterial cell wall NHD and NHD-AgNPs treated bacterial cells were observed under atomic force microscope(AFM) and treated bacterial cells were severely damaged with leaked cytoplasmic contents as compare to untreated bacterial cell. These results validate that NHD-AgNPs were highly active as compared to NHD against both strains at their MIC concentrations. In future, comparative wound healing potential will be emphasized.
MeSH term(s)	3T3 Cells ; Animals ; Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/toxicity ; Cell Wall/drug effects ; Disk Diffusion Antimicrobial Tests ; Drug Compounding ; Hydrazines/chemical synthesis ; Hydrazines/pharmacology ; Hydrazines/toxicity ; Metal Nanoparticles ; Mice ; Microscopy, Atomic Force ; Nicotinic Acids/chemical synthesis ; Nicotinic Acids/pharmacology ; Nicotinic Acids/toxicity ; Salmonella enterica/drug effects ; Salmonella enterica/growth & development ; Schiff Bases/chemical synthesis ; Schiff Bases/pharmacology ; Schiff Bases/toxicity ; Silver Compounds/chemical synthesis ; Silver Compounds/pharmacology ; Silver Compounds/toxicity
Chemical Substances	Anti-Bacterial Agents ; Hydrazines ; Nicotinic Acids ; Schiff Bases ; Silver Compounds ; nicotinic acid hydrazide (AF1LLO72TM)
Language	English
Publishing date	2021-04-06
Publishing country	Pakistan
Document type	Comparative Study ; Journal Article
ZDB-ID	885131-1
ISSN	1011-601X
ISSN	1011-601X
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Article: In silico identification of potential inhibitors against shikimate dehydrogenase through virtual screening and toxicity studies for the treatment of tuberculosis.

Isa, Mustafa Alhaji / Majumdar, Rita Singh / Haider, Shazia

International microbiology : the official journal of the Spanish Society for Microbiology

2018 Volume 22, Issue 1, Page(s) 7–17

Abstract: The present study attempts to identify the novel inhibitors of shikimate dehydrogenase (SD), the enzyme that catalyzes the fourth reaction in the shikimate pathway, through virtual screening and toxicity studies. Crystal structure of SD was obtained from ...

Abstract	The present study attempts to identify the novel inhibitors of shikimate dehydrogenase (SD), the enzyme that catalyzes the fourth reaction in the shikimate pathway, through virtual screening and toxicity studies. Crystal structure of SD was obtained from Protein Data Bank (PDB ID 4P4G, 1.7 Å) and subjected to energy minimization and structure optimization. A total of 13,803 compounds retrieved from two public databases and used for the virtual screening based on physicochemical properties (Lipinski rule of five) and molecular docking analyses. A total of 26 compounds with good AutoDock binding energies values ranging between - 12.03 and - 8.33 kcal/mol was selected and further filtered for absorption distribution metabolism excretion and toxicity analyses (ADMET). In this, eight compounds were selected, which satisfied all the ADME and toxicity analysis properties. Three compounds with better AutoDock binding energies values (ZINC12135132, - 12.03 kcal/mol; ZINC08951370, - 10.04 kcal/mol; and ZINC14733847, 9.82 kcal/mol) were considered for molecular dynamic (MD) simulation and molecular generalized born surface area (MM-GBSA) analyses. The results of the analyses revealed that the two ligands (ZINC12135132 and ZINC08951370) had better inhibitory activities within their complexes, after the 50-ns MD simulation, which suggested that the complexes formed stable conformation. It is noteworthy that compounds identified by docking, MD simulation, and MM-GBSA methods could be a drug for tuberculosis which required further experimental validation.
MeSH term(s)	Alcohol Oxidoreductases/antagonists & inhibitors ; Alcohol Oxidoreductases/chemistry ; Antitubercular Agents/chemistry ; Antitubercular Agents/isolation & purification ; Antitubercular Agents/pharmacology ; Antitubercular Agents/toxicity ; Computational Biology/methods ; Drug Evaluation, Preclinical/methods ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/isolation & purification ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/toxicity ; Molecular Docking Simulation ; Protein Binding ; Protein Conformation ; Tuberculosis/drug therapy
Chemical Substances	Antitubercular Agents ; Enzyme Inhibitors ; Alcohol Oxidoreductases (EC 1.1.-) ; Shikimate dehydrogenase (EC 1.1.1.25)
Language	English
Publishing date	2018-08-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1454951-7
ISSN	1618-1905 ; 1139-6709
ISSN (online)	1618-1905
ISSN	1139-6709
DOI	10.1007/s10123-018-0021-2
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Zs.A 4964: Show issues

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Article ; Online: In silico docking and molecular dynamics simulation of 3-dehydroquinate synthase (DHQS) from Mycobacterium tuberculosis.

Isa, Mustafa Alhaji / Majumdhar, Rita Singh / Haider, Shazia

Journal of molecular modeling

2018 Volume 24, Issue 6, Page(s) 132

Abstract: The shikimate pathway is as an attractive target because it is present in bacteria, algae, fungi, and plants but does not occur in mammals. In Mycobacterium tuberculosis (MTB), the shikimate pathway is integral to the biosynthesis of naphthoquinones, ... ...

Abstract	The shikimate pathway is as an attractive target because it is present in bacteria, algae, fungi, and plants but does not occur in mammals. In Mycobacterium tuberculosis (MTB), the shikimate pathway is integral to the biosynthesis of naphthoquinones, menaquinones, and mycobactin. In these study, novel inhibitors of 3-dehydroquinate synthase (DHQS), an enzyme that catalyzes the second step of the shikimate pathway in MTB, were determined. 12,165 compounds were selected from two public databases through virtual screening and molecular docking analysis using PyRx 8.0 and Autodock 4.2, respectively. A total of 18 compounds with the best binding energies (-13.23 to -8.22 kcal/mol) were then selected and screened for absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, and nine of those compounds were found to satisfy all of the ADME and toxicity criteria. Among those nine, the three compounds-ZINC633887 (binding energy = -10.29 kcal/mol), ZINC08983432 (-9.34 kcal/mol), and PubChem73393 (-8.61 kcal/mol)-with the best binding energies were further selected for molecular dynamics (MD) simulation analysis. The results of the 50-ns MD simulations showed that the two compounds ZINC633887 and PubChem73393 formed stable complexes with DHQS and that the structures of those two ligands remained largely unchanged at the ligand-binding site during the simulations. These two compounds identified through docking and MD simulation are potential candidates for the treatment of TB, and should undergo validation in vivo and in vitro.
MeSH term(s)	Bacterial Proteins/chemistry ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Mycobacterium tuberculosis/enzymology ; Phosphorus-Oxygen Lyases/chemistry
Chemical Substances	Bacterial Proteins ; 3-dehydroquinate synthetase (EC 4.2.3.4) ; Phosphorus-Oxygen Lyases (EC 4.6.-)
Language	English
Publishing date	2018-05-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1284729-x
ISSN	0948-5023 ; 1610-2940
ISSN (online)	0948-5023
ISSN	1610-2940
DOI	10.1007/s00894-018-3637-4
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