In silico Evaluation of the Inhibitory Potential of Cymbopogonol from Cymbopogon citratus Towards Falcipain-2 (FP2) Cysteine Protease of Plasmodium falciparum


  • Emmanuel T. Adetobi Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin 240003, Kwara, Nigeria
  • Samuel O. Akinsuyi Department of Microbiology and Cell Science, University of Florida, Gainsville, FL 32611, USA
  • Otunba A. Ahmed Daniel and Fola Biotechnology Foundation, Makoko, Lagos 101245, Nigeria
  • Elizabeth O. Folajimi Department of Microbiology, Faculty of Life Sciences, University of Ilorin, Ilorin 240003, Kwara, Nigeria
  • Benjamin A. Babalola Biochemistry Division, Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA


Malaria,, Cymbopogonol,, Falcipain-2 (FP2),, Molecular docking,, Drug discovery.


Antimicrobial resistance is a major challenge militating against the health of people globally. Plasmodium falciparum has developed resistance to current drugs used in tackling malaria, and this has remarkably contributed to an increased mortality rate in Sub-Saharan Africa. The inhibitory potential of cymbopogonol against Falcipain-2 (FP2) of the Plasmodium falciparum parasite was evaluated and achieved using a computational approach in this study. SwissADME, ADMETLab, and PROTOX-II servers were used to evaluate cymbopogonol's absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties in comparison to the other ligands. The test compound had a better docking score of – 8.40 kcal/mol compared to the standard and co-crystallized ligand. The compound also had a hydrophobic interaction with LEU I:78, MET I:29, VAL I:44, VAL I:47, LEU I:25, and ARG I:43 present in the FP2 receptor- binding motif of the malaria parasite. The compound also possesses a favorable ADMET characteristics and demonstrated no tendency towards hERG inhibition, hepatotoxicity, carcinogenicity, mutagenicity, or drug-liver injury. Therefore, cymbopogonol may be used for experimental research and future medication development for the successful treatment of malaria.



Babalola BA, Adetobi TE, Akinsuyi OS, Adebisi OA, Folajimi EO. Computational study of the therapeutic potential of novel heterocyclic derivatives against SARS-CoV-2. COVID. 2021; 1(4):757–74.

Chanda-Kapata P, Kapata N, Zumla A. COVID-19 and malaria: A symptom screening challenge for malaria endemic countries. Int J Infect Dis. 2020; 94:151–3.

Price RN, Anstey NM, Guerra CA, Yeung S, Tjitra E, White NJ. Vivax Malaria: Neglected and not benign. Am J Trop Med Hyg. 2007; 77:79–87.

Carlton JM, Adams JH, Silva JC, Bidwell SL, Lorenzi H, Caler E, Crabtree J, Angiuoli SV, Merino EF, Amedeo P, Cheng Q, Coulson RMR, Crabb BS, del Portillo HA, Essien K, Feldblyum TV, Fernandez-Becerra C, Gilson PR, Gueye AH, Guo X, Kang’a S, Kooij TWA, Korsinczky M, Meyer EVS, Nene V, Paulsen I, White O, Ralph SA, Ren Q, Sargeant TJ, Salzberg SL, Stoeckert CJ, Sullivan SA, Yamamoto MM, Hoffman SL, Wortman JR, Gardner MJ, Galinski MR, Barnwell JW & Fraser-Liggett CM. Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature. 2008; 455:757–63.

Ajibola O, Diop MF, Ghansah A, Amenga-Etego L, Golassa L, Apinjoh T, Randrianarivelojosia M, Maiga-Ascofare O, Yavo W, Bouyou-Akotet M, Oyebola KM, Andagalu B, Alessandro UD, Ishengoma D, Djimde AA, Kamau E, Amambua-Ngwa A. In silico characterisation of putative Plasmodium falciparum vaccine candidates in african malaria populations. Sci Rep 2021; 11(1):16215-16228.

World Health Organization. Disease burden, malaria. (Accessed: 11 December 2021).

Battista T, Colotti G, Ilari A, Fiorillo A. Targeting trypanothione reductase, a key enzyme in the redox trypanosomatid metabolism, to develop new drugs against leishmaniasis and trypanosomiases. Molecules. 2020; 25(8):1924.

Cox FE. History of the discovery of the malaria parasites and their vectors. Parasit Vectors. 2010; 3:5-14.

Ettari R, Previti S, Di Chio C, Zappalà M. Falcipain-2 and falcipain-3 inhibitors as promising antimalarial agents. Curr. Med. Chem. 2020; 28(15):3010-3031.

Sourabh S, Chauhan M, Tuteja R. Genome wide In Silico characterization of ded1 family of helicases from Plasmodium Falciparum. Helicases from All Domains of Life. 2019; 97– 112.

Rosenthal PJ. Falcipain cysteine proteases of malaria parasites: an update. Biochim Biophys Acta - Proteins Proteom. 2020; 1868(3):140362.

Salawu EO. In Silico Study Reveals How E64 Approaches, Binds to, and Inhibits falcipain-2 of Plasmodium falciparum that causes malaria in humans. Sci. Rep. 2018; 8(1):16380- 16393.

Pathak DP, Sharma V, Kumar S. Designing novel inhibitors against falcipain-2 of Plasmodium falciparum. Bioorg Med Chem Lett. 2018; 28(9):1566-1569.

Kumar P, Kadyan K, Duhan M, Sindhu J, Singh V, Saharan BS. Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents. Chem Cent J. 2017; 11(1):115-129.

Femi-Olabisi FJ, Ishola AA, Faokunla O, Agboola AO, Babalola BA. Evaluation of the inhibitory potentials of selected compounds from Costus spicatus (Jacq.) rhizome towards enzymes associated with insulin resistance in polycystic ovarian syndrome: an in silico study. J Genet Eng Biotechnol. 2021; 19(1):176-185.

Chukwuocha UM, Fernández-Rivera O, Legorreta-Herrera M. Exploring the antimalarial potential of whole Cymbopogon citratus plant therapy. J Ethnopharmacol. 2016; 193:517–23.

Clement YN, Baksh-Comeau YS, Seaforth CE. An ethnobotanical survey of medicinal plants in Trinidad. J Ethnobiol Ethnomedicine. 2015; 11(1):1-28.

Odoh UE, Uzor PF, Eze CL, Akunne TC, Onyegbulam CM, Osadebe PO. Medicinal plants used by the people of Nsukka Local Government Area, south-eastern Nigeria for the treatment of malaria: an ethnobotanical survey. J Ethnopharmacol. 2018; 218:1-5.

Sawadogo I, Paré A, Kaboré D, Montet D, Durand N, Bouajila J, Zida EP, Sawadogo-Lingani H, Nikiéma PA, Nebié RH, Bassolé IH. Antifungal and antiaflatoxinogenic effects of Cymbopogon citratus, Cymbopogon nardus, and Cymbopogon schoenanthus essential oils alone and in combination. J Fungi. 2022; 8(2):117.

HMDB. Ontology: Showing metabocard for cymbopogonol (HMDB0036904). es (Accessed 23rd September 2022).

Marrero AD, Quesada AR, Martínez-Poveda B, Medina MÁ. Antiangiogenic phytochemicals constituent of diet as promising candidates for chemoprevention of cancer. Antioxidants. 2022; 11(2):302-322.

Bishayee A, Ahmed S, Brankov N, Perloff M. Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front Biosci. 2011; 16(1):980-986.

Crowley VM, Ayi K, Lu Z, Liby KT, Sporn M, Kain KC. Synthetic oleanane triterpenoids enhance blood brain barrier integrity and improve survival in experimental cerebral malaria. Malar J. 2017; 16(1):463-474.

Dobreva A, Nedeltcheva-Antonova D, Nenov N, Getchovska K, Antonov L. Subcritical extracts from major species of oil- bearing roses—a comparative chemical profiling. Molecules. 2021; 26(16):4991.

Ramalhete C, da Cruz FP, Mulhovo S, Sousa IJ, Fernandes MX, Prudêncio M, Ferreira MJU. Dual-stage triterpenoids from an african medicinal plant targeting the malaria parasite. Bioorg Med Chem. 2014; 22(15):3887–90.

Assefa DG, Zeleke ED, Molla W, Mengistu N, Sefa A, Mebratu A, Bate AF, Bekele E, Yesmaw G & Makonnen E. Safety of dihydroartemisinin-piperaquine versus artemether- lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials. Malar J. 2022; 21(1):4-28.

Brinkmann S, Semmler S, Kersten C, Patras MA, Kurz M, Fuchs N, Hammerschmidt SJ, Legac J, Hammann PE, Vilcinskas A, Rosenthal PJ, Schirmeister T, Bauer A, Schäberle TF. Identification, characterization, and synthesis of natural parasitic cysteine protease inhibitors: pentacitidins are more potent falcitidin analogues. ACS Chem Biol. 2022; 17(3):576– 89.

Dong J, Wang N-N, Yao Z-J, Zhang L, Cheng Y, Ouyang D, Lu AP, Cao, DS. ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively collected ADMET database. J Cheminformatics. 2018; 10(1):29-40.

Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018; 46(W1):W257–63.

da Silva GN, Maria NR, Schuck DC, Cruz LN, de Moraes MS, Nakabashi M. Two series of new semisynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action. Malar J. 2013; 12(1):89-96.

Cátia R, Filipa PC, Silva MC, Inês JS, Miguel XF, Miguel P, Maria-José UF. Dual-stage triterpenoids from an african medicinal plant targeting the malaria parasite. Bioorg. Med. Chem. 2014; 22:3887-3890.

Bezerra KS, Fulco UL, Esmaile SC, Lima Neto JX, Machado LD, Freire VN, Albuquerque EL, Oliveira JI. Ribosomal RNA– aminoglycoside hygromycin b interaction energy calculation within a density functional theory framework. J Phys Chem B. 2019; 123(30):6421–9.

Ambrose GO, Afees OJ, Nwamaka NC, Simon N, Oluwaseun AA, Soyinka T, Oluwaseun AS, Bankole S. Selection of Luteolin as a potential antagonist from molecular docking analysis of EGFR mutant. Bioinformation. 2018; 14(05):241–7.

Guan L, Yang H, Cai Y, Sun L, Di P, Li W. ADMET-score – a comprehensive scoring function for evaluation of chemical drug-likeness. Med Chem Comm. 2019; 10(1):148–57.

Johnson TO, Adegboyega AE, Iwaloye O, Eseola OA, Plass W, Afolabi B, Rotimi D, Ahmed EI, Albrakatih A, Gaber E, Batihai GE, Adeyemi, OS. Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2. J Pharmacol Sci. 2021; 147(1):62–71.

Zhao FK, Shi RB, Sun YB, Yang SY, Chen LZ, Fang BH. A comprehensive study to identify major metabolites of an amoxicillin–sulbactam hybrid molecule in rats and its metabolic pathway using UPLC-Q-TOF-MS/MS. Metabolites. 2022; 12(7):662.

Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7(1):42717-42730.

Barber DM. A competitive edge: competitor inspired scaffold hopping in herbicide lead optimization. J Agric Food Chem. 2022; 70(36):11075–11090.

Küçüktürkmen B and Bozkır A. A new approach for drug targeting to the central nervous system. In Nanoarchitectonics in Biomedicine. William Andrew Publishing, 2019; 335–69.

Ursu O, Rayan A, Goldblum A, Oprea TI. Understanding drug- likeness. Wiley Interdiscip. Rev Comput Mol Sci. 2011; 1(5):760–81.

Soliman ME, Adewumi AT, Akawa OB, Subair TI, Okunlola FO, Akinsuku OE, Khan S. Simulation models for prediction of bioavailability of medicinal drugs—the interface between experiment and computation. AAPS Pharm Sci Tech. 2022; 23(3): 86-103.

Ogala J, Hassan Y, Samaila A, Bindawa M, Taşkın Tok T. Synthesis, antifungal activity and in silico ADMET studies of benzyl alcohol derivatives. Istanbul J Pharm. 2022; 52(1):47- 53.

van Vugt-Lussenburg BM, Capinha L, Reinen J, Rooseboom M, Kranendonk M, Onderwater RC, Jennings P. ―Commandeuring‖ Xenobiotic metabolism: advances in understanding xenobiotic metabolism. Chem Res Toxicol. 2022; 35(7):1184-201.

Jang HY, Song J, Kim JH, Lee H, Kim I-W, Moon B, Oh JM. Machine learning-based quantitative prediction of drug exposure in drug-drug interactions using drug label information. NPJ Digit Med. 2022; 5(1):88-99.

Adejoro IA, Waheed SO, Adeboye OO, Akhigbe FU. Molecular docking of the inhibitory activities of triterpenoids of Lonchocarpus cyanescens against ulcer. Biophys Chem. 2017; 08(01):1–11.

Uddin A, Gupta S, Mohammad T, Shahi D, Hussain A, Alajmi MF, Hesham R. El-Seedi HR, Hassan I, Singh S, Abid M. Target-based virtual screening of natural compounds identifies a potent antimalarial with selective falcipain-2 inhibitory activity. Front Pharmacol. 2022; 13-29.

Guerra CVC, da Silva BM, Müller P, Baia-da-Silva DC, Moura MAS, Araújo JDA, Silva JCS, Silva-Neto AV, Balieiro AAS, Costa-Martins AG, Melo GC, Val F, Bassat Q, Nakaya HI, Martinez-Espinosa FE, Lacerda M, Sampaio VZ, Monteir W. HIV infection increases the risk of acquiring Plasmodium vivax malaria: a 4-year cohort study in the Brazilian Amazon HIV and risk of vivax malaria. Sci Rep. 2022; 12(1):9076-9085.

Bromowska AK. Thermodynamics of ligand-protein interactions: implications for molecular design. Inchotech Books. 2011.

Himangini, Pathak DP, Sharma V, Kumar S. Designing novel inhibitors against falcipain-2 of Plasmodium falciparum. Bioorg Med Chem Lett. 2018; 28(9):1566–1569.

Mane UR, Gupta RC, Nadkarni SS, Giridhar RR, Naik PP, Yadav MR. Falcipain inhibitors as potential therapeutics for resistant strains of malaria: a patent review. Expert Opin Ther Pat. 2012; 23(2):165–87.

Rosenthal PJ. Falcipain cysteine proteases of malaria parasites: an update. Biochim Biophys Acta Proteins Proteom. 2020; 1868(3):140362.




How to Cite

T. Adetobi, E., O. Akinsuyi, S., A. Ahmed, O., O. Folajimi, E., & A. Babalola, B. (2022). In silico Evaluation of the Inhibitory Potential of Cymbopogonol from Cymbopogon citratus Towards Falcipain-2 (FP2) Cysteine Protease of Plasmodium falciparum: Tropical Journal of Natural Product Research (TJNPR), 6(10), 1687–1684. Retrieved from