In Silico Exploration of Antimalarial Potential of Ethanolic Leaf Extract of Heliotropium indicum
DOI:
https://doi.org/10.54548/الملخص
ABSTRACT
Heliotropium indicum, commonly known as Indian heliotrope, is a member of the family Boraginaceae, and possessed array of ethnomedicinal usefulness. The objective of this study was to computationally investigate phytochemical constituents, pharmacokinetics and binding dynamics of ethanolic leaf extract of H. indicum with key molecular targets relevant to malaria. The method used are pharmacokinetics prediction, target prediction, and molecular docking. The results showed twenty-nine (29) identified constituents of which some are poorly soluble and have low gastrointestinal absorption (GIA) and others soluble with high GIA and could permeate the blood brain barrier (BBB). The molecular docking results showed that eicosane have the highest binding affinity for Enoyl- acyl-carrier protein (ACP) reductase (-7.363 kcal.mol-1), followed by 3-oxoacyl-ACP reductase (-7.012 kcal.mol-1), and beta-hydroxyacyl-ACP dehydratase (-6.295 kcal.mol-1), while Nonadecane has binding affinity of -5.048 kcal.mol-1 for Heat shock protein 90; 2-(Pentyloxycarbonyl) benzoic acid has binding affinity of -5.375 kcal.mol-1 for cysteine protease falcipain-3, and 4-Methoxyanthranilic acid has binding affinity of -5.667 kcal.mol-1 for M17 leucyl aminopeptidase. Overall, this study showed that nonadecane, 1-chlorononadecane, eicosane, 2-(Pentyloxycarbonyl) benzoic acid, and 4-Methoxyanthranilic acid, are the five most active constituents of ethanolic leaves extract of H. indicum; targeting key proteins in P. falciparum. In conclusion, ethanolic leaves extract of H. indicum plant has potential antimalarial properties. However, further in vivo and in vitro studies are required to validate the claims of this study in order to established therapeutic efficacy of active compounds of ethanolic leaves extract of H. indicum that are directly responsible for its antimalarial properties.
Keywords: Heliotropium indicum, phytochemicals, pharmacokinetics, Plasmodium falciparum, Enoyl-ACP reductase, M17 leucyl aminopeptidase, molecular docking.
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REFERENCES
Ahsan T., Chen J., Zhao X., Irfan M. and Wu Y. (2017). Extraction and identification of bioactive compounds (eicosane and dibutyl phthalate) produced by Streptomyces strain KX852460 for the biological control of Rhizoctonia solani AG-3 strain KX852461 to control target spot disease in tobacco leaf. MB Expr. 7:54. DOI 10.1186/s13568-017-0351-z
Amusan, T., Bello, M. and Oladeji, O. (2016): Proximate, vitamin assays and anti-oxidant properties of an underutilised indigenous vegetable Heliotropium indicum L. (Lamiales: Boraginaceae) in West Africa in enhancing diet diversification. Revista Brasileira de Gestão Ambiental e Sustentabilidade: 3(6): 337-353.
Arnott, J.A., and Planey, S.L. (2012). The influence of lipophilicity in drug discovery and design. Expert Opin. Drug Discovery 7(10): 863–875.
Balachandran, A.; Choi, S.B.; Beata, M.-M.; Małgorzata, J.; Froemming, G.R.A.; Lavilla, C.A., Jr.; Billacura, M.P.; Siyumbwa, S.N.; Okechukwu, P.N. (2023). Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane. Molecules 2023, 28, 1043. https://doi.org/10.3390/molecules28031043
Boye A, Koffuor GA, Ameyaw EO and Abaitey AK (2012): Analgesic activity and safety assessment of Heliotropium indicum Linn. (Boraginaceae) in rodents. International Journal of Pharmacology, 8(2): 91-100.
Chuah, X.Q.; Okechukwu, P.N.; Amini, F.; Teo, S.S. (2018). Eicosane, pentadecane and palmitic acid: The effects in in vitro wound healing studies. Asian Pac. J. Trop. Biomed. 2018, 8, 490–499.
Daina A, Michielin O, Zoete V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Report 7(1): 42717. https://doi.org/10.1038/srep42717
Eberhardt, J., Santos-Martins, D., Tillack, A.F., and Forli, S. (2021). AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings, J. Chem. Inf. Model, 61(8): 3891-3898.
Faleye B.C., Bamisaye F.A., and Fatoki T.H. (2023). GC-MS Characterization and Computational Assessment of Phytochemicals in Heliotropium indicum Ethanolic Leaves Extract. J. Compl. Altern. Med. Res., 22(1), 1-10. DOI: 10.9734/JOCAMR/2023/v22i1447
Fatoki T. H., Awofisayo O. A., and Faleye B. C., (2022). Cipargamin Could Inhibit Human Adenosine Receptor A3 with Higher Binding Affinity than Plasmodium falciparum P-type ATPase 4: An In Silico Study. Acta facultatis medicae Naissensis 2022; 39(1): 23-36.
Fatoki T.H., Balogun C.T., Oluwadare O.T., Famusiwa C.D., Oyebiyi O.R., Ejimadu B.A., Lawal O.E., Amosun B.E., Adeyeye T.O., and Falode J.A. (2023). In Silico Evaluation of Nutri-Pharmacological Potentials of Phytochemicals in Sorghum (Sorghum bicolor) Grains. J. Food Bioact., 23. doi: 10.31665/JFB.2023.18354.
Funayama S. and Cordell G.A. (2015). Compounds Derived from Anthranilic Acid. In: Alkaloids: A Treasury of poisons and medicines. 163-180. Doi: 10.1016/B978-0-12-417302-6.00009-X
Gardiner D.L., Trenholme K.R., Skinner-Adams T.S., Stack C.M., and Dalton J.P. (2006). Overexpression of Leucyl Aminopeptidase in Plasmodium falciparum Parasites: target for the antimalarial activity of bestatin. Journal of Biological Chemistry, 281(3): 1741–1745.
Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. (2007). Relating protein pharmacology by ligand chemistry. Nature Biotech. 25(2), 197-206.
Koffuor GA, Boye A, Amoateng P, Ameyaw EO and Abaitey AK (2012): Investigating the site of action of an aqueous extract of Heliotropium indicum Linn (Boraginaceae) on smooth muscles. Research Journal of Pharmacology, 6(1): 12-19.
Kumari N., Menghani E. and Mithal R. (2019). Bioactive compounds characterization and antibacterial potentials of Actinomycetes isolated from Rhizospheric soil. Journal of Scientific and Industrial Research, 78: 793-798.
Lê, H.G.; Kang, J.-M.; Võ, T.C.; Nguyễn, T.D.; Jung, M.; Shin, M.K.; Yoo, W.G.; Na, B.-K. (2022). Inhibitor of Cysteine Protease of Plasmodium malariae Regulates Malapains, Endogenous Cysteine Proteases of the Parasite. Pathogens, 11, 605.
Martin P, Giardiello M, McDonald TO, Rannard SP, Owen A. (2013). Mediation of in vitro cytochrome P450 activity by common pharmaceutical excipients. Mol Pharm., 10:2739-2748. doi: 10.1021/mp400175n
Mathew R., Wunderlich J., Thivierge K., Cwiklinski K., Dumont C., Tilley L., Rohrbach P. and Dalton J.P. (2021). Biochemical and cellular characterisation of the Plasmodium falciparum M1 alanyl aminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP). Scientific Reports, 11:2854
McGowan, S, Oellig, CA, Birru, WA, Caradoc-Davies, TT, Stack, CM, Lowther, J, Skinner Adams, T, Mucha, A, Kafarski, P, Grembecka, J, Trenholme, KR, Buckle, AM, Gardiner, DL, Dalton, JP & Whisstock, JC (2010). Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases', Proceedings of the National Academy of Sciences (PNAS), 107(6): 2449-2454.
Morde V.A, Shaikh M.S., Pissurlenkar R.R.S. and Coutinho E.C. (2009). Molecular modeling studies, synthesis, and biological evaluation of Plasmodium falciparum enoyl-acyl carrier protein reductase (Pf ENR) inhibitors. Mol Divers. 13:501–517 DOI 10.1007/s11030-009-9141-0
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. Journal of Computational Chemistry 30(16):2785–2791. https://doi.org/10.1002/jcc.21256
Muthulakshmi, A., Margret, J. R. and Mohan, V. R. (2012). GC-MS Analysis of Bioactive components of Feonia elephantum correa (Rutaceae). J. App. Pharm. Sci. 2 (2):69-74.
Nandhini SU (2015). Gas chromatography–mass spectrometry analysis of bioactive constituents from the marine Streptomyces. Asi J Pharm Clin Res., 8:244–246
Nicola G, Smith CA, Lucumi E, Kuo MR, Karagyozov L, Fidock DA, Sacchettini JC, Abagyan R (2007). Discovery of novel inhibitors targeting enoyl-acyl carrier protein reductase in Plasmodium falciparum by structure-based virtual screening. Biochem Biophys Res Commun 358:686–691. doi:10.1016/j.bbrc.2007.04.113
Okechukwu N.P. (2020). Evaluation of Anti-Inflammatory, Analgesic, Antipyretic Effect of Eicosane, Pentadecane, Octacosane, and Heneicosane. Asian J Pharm Clin Res, 13(4): 29-35.
Pandey KC, Singh N, Arastu-Kapur S, Bogyo M, Rosenthal PJ (2006). Falstatin, a cysteine protease inhibitor of Plasmodium falciparum, facilitates erythrocyte invasion. PLoS Pathog 2(11): e117.
Pant, A., Kumar, R., Wani, N A., Verma, S., Sharma, R., Pande V., Saxena A. K., Dixit R., Rai R., and Pandey K. C. (2018) Allosteric Site Inhibitor Disrupting Auto-Processing of Malarial Cysteine Proteases Scientific Reports, 8: 16193.
Saeed S., Tremp A.Z. and Dessens J.T. (2023). Plasmodium berghei oocysts possess fatty acid synthesis and scavenging routes. Scientific Reports, 13:12700.
Sharma S.K., Kapoor M., Ramya T. N. C., Kumar S., Kumar G., Modak R., Sharma S., Surolia N., and Surolia A. (2003). Identification, Characterization, and Inhibition of Plasmodium falciparum β-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ). Journal of Biological Chemistry, 278(46): 45661–45671.
Stierand K, Maaß PC, Rarey M. (2006). Molecular complexes at a glance: Automated generation of two-dimensional complex diagrams. Bioinformatics, 22:1710–1716.
Trott O, Olson AJ (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry 31(2):455–461.
Tyagi T. and Agarwal M. (2017). Phytochemicals screening and GC-MS analysis of bioactive constituents in the ethanolic extract of Pista stratiotes L. and Eichhornia crassipes (Mart.) solms, J. Pharmacog. Phytochem., 6(1):195-206.
World Health Organization (2021). World malaria report 2021 Vol. 2021. World Health Organization: Geneva, Switzerland.
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