Natural Compounds as Inhibitors of Plasmodium Falciparum Enoyl-acyl Carrier Protein Reductase (PfENR): An In silico Study

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.

Download Full-text

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

Acta Chimica Asiana ◽

10.29303/aca.v3i1.14 ◽

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.

Download Full-text

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

Qanun Medika - Medical Journal Faculty of Medicine Muhammadiyah Surabaya ◽

10.30651/jqm.v5i2.5368 ◽

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.

Download Full-text

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

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2008.12.028 ◽

2009 ◽

Vol 44 (7) ◽

pp. 3009-3019 ◽

Cited By ~ 18

Author(s):

Vladimir Frecer ◽

Eugene Megnassan ◽

Stanislav Miertus

Keyword(s):

Plasmodium Falciparum ◽

In Silico ◽

Combinatorial Library ◽

Acyl Carrier Protein ◽

Carrier Protein ◽

In Silico Screening

Download Full-text

Inhibitory Effect of Active Substances of Lollyfish (Holothuria atra) Against the Development of Plasmodium falciparum Based on In Silico Study

ILMU KELAUTAN Indonesian Journal of Marine Sciences ◽

10.14710/ik.ijms.25.4.135-142 ◽

2020 ◽

Vol 25 (4) ◽

pp. 135-142

Author(s):

Felly Moelyadi ◽

Prawesty Diah Utami ◽

Irmawati M. Dikman

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Drug ◽

In Silico ◽

Lethal Dose ◽

Artemisinin Resistance ◽

Inhibitory Effect ◽

In Silico Study ◽

Carbon Dioxide Co2 ◽

Holothuria Atra ◽

Active Substances

The high level of artemisinin resistance as the antimalarial drug makes the active substances found of lollyfish (Holothuria atra) become a very useful discovery as a new antimalarial drug. The purpose of this research is to find out the inhibitory effect of the active substances of lollyfish against the development of Plasmodium falciparum with in silico method. This is a one-shot experimental study research. Based on the test of potentially active substances of lollyfish through PubChem (https://pubchem.ncbi.nlm.nih.gov/), there are pyrogallol and catechin that have potential as the antimalarial drug. Pyrogallol, chlorogenic acid, catechin dan ascorbic acid have indirect inhibition to P. falciparum Orotidine 5-Monophosphate Decarboxylase (PfOMPDC) through carbon dioxide (CO2) and it is visualized by STITCH DB Version 5.0 (http://stitch.embl.de/). The binding affinity score of catechin, obtained from molecular docking, is higher than other substances and artemisinin. The Physicochemical and pharmacokinetic activity of the substance was predicted through SWISS ADME (http://www.swissadme.ch/index.php), while the toxicity was predicted through Pro-Tox (http://tox.charite.de/protox_II/). Catechin is a substance in lollyfish that is the safest because its lowest toxicity and very effective to be used as the antimalarial drug because of its high lethal dose 50 (LD50). Therefore, active substances in lollyfish have inhibitory effects against the development of P. falciparum based on in silico study.

Download Full-text