Design and in silico screening of combinatorial library of antimalarial analogs of triclosan inhibiting Plasmodium falciparum enoyl-acyl carrier protein reductase

2009 ◽  
Vol 44 (7) ◽  
pp. 3009-3019 ◽  
Author(s):  
Vladimir Frecer ◽  
Eugene Megnassan ◽  
Stanislav Miertus
Keyword(s):  
Plasmodium Falciparum ◽  
In Silico ◽  
Combinatorial Library ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
In Silico Screening

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.

scholarly journals Analysis Docking Of Plasmodium Falciparum Enoyl Acyl Carrier Protein Reductase (Pfenr) With Organic Compunds From Virtual Screening Of Herbal Database

2020 ◽  
Vol 3 (1) ◽  
pp. 127
Author(s):  
Nya Daniaty Malau ◽  
St Fatimah Azzahra
Keyword(s):  
Plasmodium Falciparum ◽  
Virtual Screening ◽  
In Silico ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Chemotherapeutic Agents ◽  
Effective Vaccine ◽  
Carrier Protein ◽  
Autodock Vina ◽  
In Silico Screening

Malaria is one of problematic infectious diseases worldwide. The absence of an effective vaccine and the spread of drug resistant strains of Plasmodium clearly indicate the necessity for the deveploment of new chemotherapeutic agents. Recent method being developed is searching a new drug of antimalarial using in silico screening, or also known as virtual screening. One of enzyme target that important for growth of the malaria parasite is Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase (PfENR). Inhibition of this enzyme cause the fatty acid biosynthesis type II will be terminated. In this research, in silico screening was performed using AUTODOCK VINA software to find inhibitor candidates of PfENR by using ligands from the database of Medicinal Plants in Indonesia. On the AUTODOCK VINA software moleculer docking experiments were performed between ligands and macromolecule target PfENR. This target that has been optimized with residue removal and charges addition. Ligand is expected to be the PfENR inhibitors.

scholarly journals Structure-Based Design and in Silico Screening of Virtual Combinatorial Library of Benzamides Inhibiting 2-trans Enoyl-Acyl Carrier Protein Reductase of Mycobacterium tuberculosis with Favorable Predicted Pharmacokinetic Profiles

2019 ◽  
Vol 20 (19) ◽  
pp. 4730
Author(s):  
Koffi Charles Kouman ◽  
Melalie Keita ◽  
Raymond Kre N’Guessan ◽  
Luc Calvin Owono Owono ◽  
Eugene Megnassan ◽  
...  
Keyword(s):  
Gas Phase ◽  
In Silico ◽  
Combinatorial Library ◽  
Acyl Carrier Protein ◽  
Pharmacophore Model ◽  
Qsar Model ◽  
Active Conformation ◽  
In Silico Screening ◽  
Lipinski’S Rule ◽  
Pharmacokinetic Profiles

Background: During the previous decade a new class of benzamide-based inhibitors of 2-trans enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis (Mt) with unusual binding mode have emerged. Here we report in silico design and evaluation of novel benzamide InhA-Mt inhibitors with favorable predicted pharmacokinetic profiles. Methods: By using in situ modifications of the crystal structure of N-benzyl-4-((heteroaryl)methyl) benzamide (BHMB)-InhA complex (PDB entry 4QXM), 3D models of InhA-BHMBx complexes were prepared for a training set of 19 BHMBs with experimentally determined inhibitory potencies (half-maximal inhibitory concentrations IC50exp). In the search for active conformation of the BHMB1-19, linear QSAR model was prepared, which correlated computed gas phase enthalpies of formation (∆∆HMM) of InhA-BHMBx complexes with the IC50exp. Further, taking into account the solvent effect and entropy changes upon ligand, binding resulted in a superior QSAR model correlating computed complexation Gibbs free energies (∆∆Gcom). The successive pharmacophore model (PH4) generated from the active conformations of BHMBs served as a virtual screening tool of novel analogs included in a virtual combinatorial library (VCL) of compounds containing benzamide scaffolds. The VCL filtered by Lipinski’s rule-of-five was screened by the PH4 model to identify new BHMB analogs. Results: Gas phase QSAR model: −log10(IC50exp) = pIC50exp = −0.2465 × ∆∆HMM + 7.95503, R2 = 0.94; superior aqueous phase QSAR model: pIC50exp = −0.2370 × ∆∆Gcom + 7.8783, R2 = 0.97 and PH4 pharmacophore model: p IC 50 exp = 1.0013 × p IC 50 exp − 0.0085, R2 = 0.95. The VCL of more than 114 thousand BHMBs was filtered down to 73,565 analogs Lipinski’s rule. The five-point PH4 screening retained 90 new and potent BHMBs with predicted inhibitory potencies IC50pre up to 65 times lower than that of BHMB1 (IC50exp = 20 nM). Predicted pharmacokinetic profile of the new analogs showed enhanced cell membrane permeability and high human oral absorption compared to current anti-tuberculotics. Conclusions: Combined use of QSAR models that considered binding of the BHMBs to InhA, pharmacophore model, and ADME properties helped to recognize bound active conformation of the benzamide inhibitors, permitted in silico screening of VCL of compounds sharing benzamide scaffold and identification of new analogs with predicted high inhibitory potencies and favorable pharmacokinetic profiles.

scholarly journals The Effect of Thespesia populnea Against Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase Receptor by Study In Silico

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
I Made Prasetya Kurniawan ◽  
Prawesty Diah Utami ◽  
Risma Risma
Keyword(s):  
Plasmodium Falciparum ◽  
Active Compound ◽  
In Silico ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Active Compounds ◽  
Prediction Analysis ◽  
Thespesia Populnea ◽  
Study Results ◽  
In Silico Studies

Indonesia is a country that has abundant natural resources; one of them is the Baru laut plant which is the latest breakthrough because it has an active substance that can be used as an anti-malaria medicine. It is very beneficial because there has been a case of resistance of artemisinin derivatives in Indonesia. The purpose of this study was to determine the potential of active compounds in Baru laut plants (Thespesia populnea (L.) Soland ex. Correa) against the Plasmodium falciparum enoyl acyl carrier protein reductase receptor in P. falciparum through in silico studies. This research is purely experimental using the One-Shot Experimental Study research design method. Observations were only made once between the variables studied through three analyzes, namely prediction analysis of active compound content, prediction analysis of the mechanism of action of active compound content, and prediction analysis of ADME active compound. The study results show that there are three active compounds in Baru laut plants that have antimalarial potential. The three compounds include gossypol, linoleic acid, and beta-sitosterol, have their respective potential in becoming a malaria drug. This study concludes that Baru laut plants have potential as anti-malaria drugs.

scholarly journals In Silico Screening of a Novel Inhibitor of β-Ketoacyl Acyl Carrier Protein Synthase I

2011 ◽  
Vol 32 (5) ◽  
pp. 1645-1649 ◽  
Author(s):  
Jee-Young Lee ◽  
Ki-Woong Jeong ◽  
Ju-Un Lee ◽  
Dong-Il Kang ◽  
Yang-Mee Kim
Keyword(s):  
In Silico ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
In Silico Screening

scholarly journals In silico screening for Plasmodium falciparum enoyl-ACP reductase inhibitors

2014 ◽  
Vol 29 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Steffen Lindert ◽  
Lorillee Tallorin ◽  
Quynh G. Nguyen ◽  
Michael D. Burkart ◽  
J. Andrew McCammon
Keyword(s):  
Plasmodium Falciparum ◽  
In Silico ◽  
In Silico Screening ◽  
Reductase Inhibitors ◽  
Enoyl Acp Reductase

Structural basis for the functional and inhibitory mechanisms of β-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Plasmodium falciparum

2011 ◽  
Vol 176 (2) ◽  
pp. 238-249 ◽  
Author(s):  
Koustav Maity ◽  
Bharat Somireddy Venkata ◽  
Neha Kapoor ◽  
Namita Surolia ◽  
Avadhesha Surolia ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Acyl Carrier Protein ◽  
Structural Basis ◽  
Carrier Protein ◽  
Inhibitory Mechanisms
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