scholarly journals In silico Approach to Identify Potent Bioactive Compounds as Inhibitors against the Enoyl-acyl Carrier Protein (acp) Reductase Enzyme of Mycobacterium tuberculosis

2021 ◽  
Vol 12 (5) ◽  
pp. 7023-7039
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Bioactive Compounds ◽  
In Silico ◽  
Acyl Carrier Protein ◽  
Cell Wall Protein ◽  
Carrier Protein ◽  
Protein Inhibitor ◽  
Mycobacterial Cell Wall ◽  
Docking Energy

The enoyl-acyl carrier protein (ACP) reductase (InhA) of Mycobacterium tuberculosis elongates acyl fatty acids, which are progenitors of mycolic acids and that are mycobacterial cell wall parts. The aim is to discover potent therapeutic novel bioactive compounds as enoyl-acyl carrier protein (ACP) reductase (InhA, PDB ID: 4U0J) antagonists using an in silico drug design scheme. Structure-based computerized prediction of drug-receptor interactions. PyRx virtual screening tool was used to conduct molecular docking investigations on enoyl-ACP reductase. A target-based ligand selection strategy to choose ligand compounds was employed. The ligand structure was chosen using LEA3D-CNRS. Medication data set that was approved by the FDA: 2028 molecule (s) were used in the study. Around 27 bioactive molecules can bind to the 4U0J, with docking scores ranging from -6.2 to -11.2 Kcal/mol. Compound CHEMBL441373 was shown to have the highest acceptable docking energy (-11.1Kcal/mol), making it a good candidate for a cell wall protein inhibitor (4U0J) that should be investigated further in vivo and in vitro. The anti-mycobacterial ability of triazole scaffolding in a new therapeutic was determined. Compound CHEMBL441373 is located to possess high docking energy (-11.1Kcal/mol) and is shown as a suitable molecule of cell wall protein inhibitor (4U0J).

scholarly journals Docking-Based Virtual Screening and Molecular Dynamics Simulations of Quercetin Analogs as Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors of Mycobacterium tuberculosis

2021 ◽  
Vol 89 (2) ◽  
pp. 20
Author(s):  
Dian Ayu Eka Pitaloka ◽  
Dwi Syah Fitra Ramadhan ◽  
Arfan ◽  
Lidya Chaidir ◽  
Taufik Muhammad Fakih
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Virtual Screening ◽  
Acyl Carrier Protein ◽  
Binding Free Energy ◽  
Multidrug Resistant ◽  
Carrier Protein ◽  
Dynamic Simulations ◽  
Energy Prediction ◽  
Dynamics Simulations ◽  
Mycobacterial Cell Wall

The emergence of multidrug-resistant Mycobacterium tuberculosis (MTB) has become a major problem in treating tuberculosis (TB) and shows the need to develop new and efficient drugs for better TB control. This study aimed to use in silico techniques to discover potential inhibitors to the Enoyl-[acyl-carrier-protein] reductase (InhA), which controls mycobacterial cell wall construction. Initially, 391 quercetin analogs present in the KNApSAck_3D database were selected, filters were sequentially applied by docking-based virtual screening. After recategorizing the variables (bond energy prediction and molecular interaction, including hydrogen bond and hydrophobic bond), compounds C00013874, C00006532, and C00013887 were selected as hit ligands. These compounds showed great hydrophobic contributions, and for each hit ligand, 100 ns of molecular dynamic simulations were performed, and the binding free energy was calculated. C00013874 demonstrated the greatest capacity for the InhA enzyme inhibition with ΔGbind = −148.651 kcal/mol compare to NAD (native ligand) presented a ΔGbind = −87.570 kcal/mol. These data are preliminary studies and might be a suitable candidate for further experimental analysis.

scholarly journals Uji In Vitro dan Studi In Silico Senyawa Turunan n’-benzoylisonicotinohydr

2019 ◽  
Vol 17 (2) ◽  
pp. 218
Author(s):  
Ruswanto Ruswanto ◽  
Nur Rahayuningsih ◽  
Nur Laeli Dwi Hidayati ◽  
Ginna Sri Nuryani ◽  
Richa Mardianingrum
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Binding Affinity ◽  
In Silico ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Inhibitor Concentration

Telah dilakukannya penelitian tentang studi in vitro dan in silico senyawa turunan N-Benzoylisonicotinohydrazide. Penelitian ini bertujuan untuk mengetahui bahwa senyawa turunan N’-benzoylisonicotinohydrazide dapat menghambat aktivitas bakteri gram positif, gram negatif dan Mycobacterium tuberculosis, serta mempunyai interaksi yang baik dengan Enoyl-Acyl Carrier Protein Reductase dari Mycobacterium Tuberculosis. Dari uji in vitro dihasilkan bahwa senyawa N’-benzoylisonicotinohydrazide memiliki Minimum Inhibitor Concentration (MIC) sebesar 0,33 µg/ml terhadap bakteri Basillus subtilis, sedangkan besarnya Minimum Inhibitor Concentration (MIC) senyawa N’-(2-chlorobenzoyl)isonicotinohydrazide terhadap Mycobacterium tuberkulosis (H37Rv) adalah sebesar 3,125 µg/ml. Dari studi in silico didapat bahwa nilai binding affinity antara senyawa N’-(2-chlorobenzoyl)isonicotinohydrazide enzim Enoyl-Acyl Carrier Protein Reductase (2X23) mempunyai binding affinity yang paling kecil sehingga dapat diprediksi bahwa senyawa tersebut mempunyai interaksi yang stabil dan paling baik disbanding senyawa-senyawa lainnya sehingga senyawa N’-(2-chlorobenzoyl)isonicotinohydrazide dapat digunakan sebagai kandidat antituberkulosis yang lebih poten.

scholarly journals Anti-TB Evaluation of Novel 2,3-Dihydroquinazolin-4(1H)-Ones and in Silico Studies of The Active Compounds

2021 ◽  
Author(s):  
Apurba Dutta ◽  
Priyanka Trivedi ◽  
Dipshikha Gogoi ◽  
Pankaj Chetia ◽  
Vinita Chaturvedi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Minimum Inhibitory Concentration ◽  
Active Site ◽  
In Silico ◽  
Inhibitory Concentration ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
In Silico Studies

Abstract In vitro anti-tubercular activity of a series of 15 novel 2,3-dihydroquinazolin-4(1H)-one analogues were evaluated against Mycobacterium tuberculosis H37Ra (ATCC 25177 strain). Among the series, seven compounds showed moderate to good anti-TB activity with minimum inhibitory concentration (MIC) values ranging from 25.0-12.5 μg/mL. Further, in silico experiments were carried out to identify the probable ligand-protein interaction. Molecular docking of the target compounds into the active site of enzymes 1DQY Antigen 85C from Mycobacterium Tuberculosis and 2NSD Enoyl Acyl Carrier Protein Reductase reveals notable information on the possible binding interactions.

scholarly journals IN-SILICO SCREENING AGAINST ANTIMALARIAL TARGET PLASMODIUM FALCIPARUM ENOYL-ACYL CARRIER PROTEIN REDUCTASE

2017 ◽  
Vol 10 (17) ◽  
pp. 127
Author(s):  
Berwi Fazri Pamudi ◽  
Azizahwati Azizahwati ◽  
Arry Yanuar
Keyword(s):  
Plasmodium Falciparum ◽  
Virtual Screening ◽  
In Silico ◽  
Acyl Carrier Protein ◽  
Parasitic Infection ◽  
Antimalarial Drugs ◽  
Chemotherapeutic Agents ◽  
Effective Vaccine ◽  
Carrier Protein ◽  
In Silico Screening

  Objective: Malaria is a parasitic infection that causes worldwide health problems. The absence of an effective vaccine and Plasmodium strains that are resistant to antimalarial drugs emphasize the importance of developing new chemotherapeutic agents. The use of computers for in-silico screening, or virtual screening, is currently being developed as a method for discovering antimalarial drugs. One of the enzymes that can support the development of the malaria parasite is the Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR). Inhibition of these enzymes leads to Type II lipid biosynthesis inhibition on the parasite.Methods: This research investigates the use of virtual screening to find PfENR inhibitor candidates. A molecular docking method using GOLD software and the medicinal plants in Indonesia database will be used. This target has been optimized by the removal of residues and the addition of charge. Ligand is expected to be an inhibitor of PfENR.Results: In-silico screening, or virtual screening, found that the top five compounds with the highest GOLD score at trial are kaempferol 3-rhamnosyl- (1-3)-rhamnosyl-(1-6)-glucoside; cyanidin 3,5-di-(6-malonylglucoside); 8-hydroxyapigenin 8-(2’’, 4’’-disulfato glucuronide); epigallocatechin 3,5,-di- O-gallat; quercetin 3,4’-dimethyl ether 7-alpha-L-arabinofuranosyl-(1-6)-glucoside. They had GOLD scores of 94.73, 95.90, 86.46, 85.39, and 84.40, respectively.Conclusions: There are two candidate inhibitor compounds from tea (Camellia sinensis), which have potential for development as an antimalarial drug, which are kaempferol 3-rhamnosyl-(1-3)-rhamnosyl-(1-6)-glucoside and epigallocatechin 3,5,-di-O-gallate, with a GOLD score of 94.73 and 85.39, respectively.

Piperazine derivatives: Synthesis, inhibition of the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase and SAR studies

2015 ◽  
Vol 90 ◽  
pp. 436-447 ◽  
Author(s):  
Mariane Rotta ◽  
Kenia Pissinate ◽  
Anne Drumond Villela ◽  
Davi Fernando Back ◽  
Luis Fernando Saraiva Macedo Timmers ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Synthesis Inhibition ◽  
Piperazine Derivatives ◽  
Sar Studies
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