LC-MS Chemical Profiling, In Silico Docking Studies to Unravel the Therapeutic Potential of <i>Streptomyces hygroscopicus</i> as a Source of Antimalarial Bioactive Compounds


  • Afifah A. Farahdina Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia;
  • Sawitri A. Ardiyanti Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia;
  • Agustina T. Endharti Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia;
  • Loeki E. Fitri Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia;
  • Nashi Widodo Department of Biology Faculty of Mathematics and Natural science, Universitas Brawijaya, Malang, East Java, 65145, Indonesia



Streptomyces hygroscopicus, molecular docking, LC-MS, Fraction 42


Malaria is a disease transmitted through the bite of female Anopheles mosquitoes carrying Plasmodium parasite. The resistance of the Plasmodium parasite against antimalarial drugs is a critical health concern necessitating the development of novel antimalarial treatments. Previous investigations reported that the crude extract of Streptomyces hygroscopicus Subsp. Hygroscopicus (S. hygroscopicus) possessed antimalarial properties, with in vitro assays confirming the ability to inhibit Plasmodium growth. Therefore, this research aimed to identify derivative compounds from S. hygroscopicus using Liquid Chromatography-Mass Spectrometry (LC-MS) and assess antimalarial activity by examining the binding site, pharmacokinetic profiles, and binding interactions through in silico analysis. In silico reverse molecular docking study was conducted with target proteins including Plasmodium falciparum malarial M1 aminopeptidase (PfA-M1), Plasmodium falciparum chloroquine resistance transporter (PfCRT), and falcipain-2 protease obtained from Protein Data Bank (PDB) and active compound ligands retrieved from PubChem. In addition, the analysis of pharmacokinetic profiles and bond interactions was performed using the SwissADME web tool and LigPlot software, respectively. The LC-MS analysis results showed that four compounds including dibenzyl amine, sedanolide, levalbuterol, and dibutyl phthalate with high retention times met the drug similarity criteria and had binding affinity values comparable to control ligands of the respective target proteins. The four compounds may have antimalarial activity due to the formation of hydrogen and hydrophobic bonds identical to those found between the target proteins and control ligands. Specifically, dibenzyl amine expressed the highest binding affinity across all target proteins, suggesting it as a potential antimalarial candidate.

Author Biography

Loeki E. Fitri, Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia;

AIDS, Toxoplasma, Opportunistic Diseases and Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia;


Nchinda TC. Malaria: a reemerging disease in Africa. Emerg Infect Dis. 1998;4(3):398-403.

Rollando R, Maulada F, Afthoni MH, Monica E, Yuniati Y, Nugraha AT. Screening Carica papaya compounds as an antimalarial agent: In silico study. Trop J Nat Prod Res. 2023;7(5):2895-2903.

Paengsri W, Promsawan N, Baramee A. Synthesis and evaluation of 2-hydroxy-1, 4-naphthoquinone derivatives as potent antimalarial agents. Chem Pharm B. 2021;69(3):253-7.

WHO. World malaria report 2020: 20 years of global progress and challenges. 2020: xiv-xv

Ministry of Health of the Republic of Indonesia. Malaria Annual Report 2022:18.

Fola AA, Feleke SM, Mohammed H, Brhane BG, Hennelly CM, Assefa A, Crudal RM, Reichert E, Juliano JJ, Cunningham J, Mamo H, Solomon H,

Tasew G, Petros B, Parr JB, Bailey JA. Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia. Nat Microbiol. 2023;8(10):1911-1919.

Fitri LE, Pawestri AR, Winaris N, Endharti AT, Khotimah ARH, Abidah HY, Huwae JTR. Antimalarial drug resistance: A brief history of its spread in

Indonesia. Drug Des Devel Ther. 2023;17:1995–201

Nugraha RY, Faratisha IF, Mardhiyyah K, Ariel DG, Putri FF, Winarsih S. Nafisatuzzamrudah, Sardjono TW, Fitri LE. Antimalarial properties of isoquinoline derivative from Streptomyces hygroscopicus subsp. Hygroscopicus: an in silico approach. BioMed Res Inter. 2020; Article ID 6135696.

Ferreira LG, Dos Santos RN, Oliva G, Andricopulo AD. Molecular docking and structure-based drug design strategies. Mol. 2015;20(7):13384-421.

Cahyono AW, Fitri LE, Nafisatuzzamrudah, Nugraha RY, Aulia R, Febriliani F, Ariel DG, Mardhiyyah K, Winarsih S, Suciati, Japany D, Endang E,

Waluyo D, Non-Toxic fractions of Streptomyces hygroscopicus Subsp. Hygroscopicus metabolite suppressed the growth of Plasmodium falciparum in vitro possibly through L-malate: Quinone Oxidoreductase (PfMQO) mitochondrial enzyme inhibition. Sys Rev Pharm. 2020;11(10):524-31.

Fitri LE, Putri AM, Erwan NE, Putri FF, Nugraha RY, SardjonoTW, Mardhiyyah K, Ariel DG, Faratisha IF, Suciati, Ihsan BR, Winarsih S, Antimalarial properties of Streptomyces hygroscopicus subsp hygroscopicus secondary metabolite active fractions: in silico and in vivo analysis. Inter J Pharm Res. 2021;13(1):2553-67.

Wettersten HI, Ganti S, Weiss RH. Metabolomic profiling of tumor-bearing mice. In Met in Enz. Acad Press. 2014;543:275-296.

Egan TJ, Kuter D. Dual-functioning antimalarials that inhibit the chloroquine-resistance transporter. Fut Micro. 2013;8(4):475-89.

Woods JA, Jewell C, O'Brien NM. Sedanolide, a natural phthalide from celery seed oil: effect on hydrogen peroxide and tert-butyl hydroperoxide-induced toxicity in HepG2 and CaCo-2 human cell lines. In Vit & Mol Tox: J Bas App Res. 2001;14(3):233-40.

Quintanilla LR, Mata CB, Vargas VJ, Bazaldúa RA, Ángeles HI, Garza GN, Hernandez GM, Antiprotozoal activity against Entamoeba histolytica of plants used in northeast Mexican traditional medicine. Bioactive compounds from Lippia graveolens and Ruta chalepensis. Mol. 2014; 19(12):21044-65.

Husain DR, Wardhani R. Antibacterial activity of endosymbiotic bacterial compound from Pheretima sp. earthworms inhibit the growth of Salmonella Typhi and Staphylococcus aureus: in vitro and in silico approach. Iranian J. Micro. 2021;13(4):537.

Flydal MI, Kråkenes TA, Tai MD, Tran MP, Teigen K, Martinez A. Levalbuterol lowers the feedback inhibition by dopamine and delays misfolding and aggregation in tyrosine hydroxylase. Biochimie. 2021;183:126-32.

Jat KR, Khairwa A. Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis. Pulmo Phar Ther. 2013;26(2):239-48.

Wang K, Yang H, Tang L. Virtual development of COVID-19 drugs targeting Nsp16-Nsp10 complex. J. Stud Res. 2023; 12(2).

Mahmud F, Lai NS, How SE, Gansau JA, Mustaffa KMF, Leow CH, Osman H, Sidek HM, Embi N, Lee PC. Bioactivities and mode of actions of dibutyl phthalates and nocardamine from Streptomyces sp. H11809. Mol. 2022; 27(7):2292.

Li Y, Meng Q, Yang M, Liu D, Hou X, Tang L, Wang X, Lyu Y, Chen X, Liu K, Yu AM. Current trends in drug metabolism and pharmacokinetics. Acta Pharm Sin B. 2019; 9(6):1113-44.

Chaira T, Subramani C, Barman TK. ADME, pharmacokinetic scaling, pharmacodynamic and prediction of human dose and regimen of novel antiviral drugs. Pharmaceutics. 2023;15(4):1212.

Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharm Tox Met. 2000; 44(1):235-49.

Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J. Med Chem. 2002; 45(12):2615-23.

Duru CE, Duru IA, Ikpa CBC, Enenebeaku UE, Obiagwu IC, Igbomezie MC, Nnabuchi MA. In silico docking studies of bioactive compounds in Ocimum gratissimum essential oil against candidapepsin-1 enzyme from Candida albicans. Trop J Nat Prod Res. 2021;5(2):364-369.

Seo S, Choi J, Park S, Ahn J. Binding affinity prediction for protein–ligand complex using deep attention mechanism based on intermolecular interactions. BMC Bioinformatics 2021;22:542.

Davarcioglu B. The general characteristic of weak intermolecular interactions in liquids and crystals. Inter J. Mod Eng Res. 2011;1(2):443-54.

Patil R, Das S, Stanley A, Yadav L, Sudhakar A, Varma AK. Optimized hydrophobic interactions and hydrogen bonding at the target-ligand interface leads the pathways of drug-designing. PLoS One. 2010;16;5(8):e12029.

Mansouri M, Daware K,Webb CT, McGowan S. Understanding the structure and function of Plasmodium aminopeptidases to facilitate drug discovery. Curr. Opin. Struct. Biol. 2023; 82:102693.

Wicht KJ, Mok S and Fidock DA. Molecular mechanisms of drug resistance in Plasmodium falciparum malaria. Ann Rev Micro. 2020;74:431-454.

Kim J, Tan YZ, Wicht KJ, Erramilli SK, Dhingra SK, Okombo J, Vendome J, Hagenah, LM, Giacometti SI, Warren AL. and Nosol K. Structure and drug resistance of the Plasmodium falciparum transporter PfCRT. Nat. 2019;576(7786):315-320.

Machin JM., Kantsadi AL. and Vakonakis I. The complex of Plasmodium falciparum falcipain-2 protease with an (E)-chalcone-based inhibitor highlights a novel, small, molecule-binding site. Malar. J. 2019;18(1):388.




How to Cite

Farahdina, A. A., Ardiyanti, S. A., Endharti, A. T., Fitri, L. E., & Widodo, N. (2024). LC-MS Chemical Profiling, In Silico Docking Studies to Unravel the Therapeutic Potential of <i>Streptomyces hygroscopicus</i> as a Source of Antimalarial Bioactive Compounds. Tropical Journal of Natural Product Research (TJNPR), 8(3), 6736–6743.

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