LEAD MOLECULE IDENTIFICATION FROM VITEX TRIFOLIA LINN FOR HELMINTHIASIS USING IN VITRO AND IN SILICO METHODS

  • SOUNDARARAJAN MUTHUKRISHNAN Department of Pharmacology, Sankaralingam Bhuvaneshwari College of Pharmacy, Sivakasi, TamilNadu, India, Department of Pharmacology, Karavali College of Pharmacy, Mangalore, India, Department of Pharmacy, Annamalai University, Chidambaram, Tamil Nadu, India
  • RAGUNATH G. Department of Pharmacology, Sankaralingam Bhuvaneshwari College of Pharmacy, Sivakasi, TamilNadu, India, Department of Pharmacology, Kamalakshi Pandurangan College of Pharmacy, Thiruvannamalai, India
  • BLESSY SUSAN VARGHESE Department of Pharmacology, Sankaralingam Bhuvaneshwari College of Pharmacy, Sivakasi, TamilNadu, India

Abstract

Objective: The study was an attempt to discover a lead molecule to treat helminthiasis using Vitex trifolia. Linn (V. folia Linn) through sterile effect, in vitro and in silico evaluation.


Methods: The antibacterial activity was done by Kirby-Bauer disc diffusion method in three different concentrations of extract and in vitro anthelmintic activity was carried out by petri dish and organ bath method. Further, the in silico docking studies were carried out by 11 phytoconstituents against phosphoethanolamine methyltransferase (4FGZ) using Auto Dock 4.2, it was working based on the principle of Lamarckian genetic algorithm. In docking studies, three important parameters such as binding energy, inhibition constant and intermolecular energy are determined.


Results: The extracts showed an antibacterial effect in three different concentrations. At 16 mcg/disc a significant effect was observed when compared to blank and ciprofloxacin 5 mcg/disc. The anthelmintic activity in the petri dish method, means paralyzing time of Pheretimaposthuma with the dose of 25, 50 and 100 mg/ml were 13.78, 5.79 and 4.57 min respectively and Piperazine citrate (10 mg/ml) showed paralysis in 21.58 min. In the organ bath method, the time for paralysis of the worm was recorded on a slow-moving Sherrington rotating drum and the study report showed that paralyzing time was decreased at increasing concentrations of the extract. The results of in silico studies exhibited a binding energy of-10.25kcal/mol, inhibitory constant (Ki) 30.91nM, intermolecular energy,-10.84kcal/mol for abietatriene-3-ol which is lesser than the standard ligand phosphoethanolamine (-6.03kcal/mol, 38.29µM,-7.82kcal/mol) respectively.


Conclusion: The study reports conclude that the active constituents in V. folia Linn having better anthelmintic activity, thus the active constituents may be optimized and make way to a new moiety for the treatment of helminthiasis.

Keywords: V. trifolia, Helminthiasis, Binding energy, Inhibitory constant, Intermolecular energy, Phosphoethanolamine methyltransferase, Abietatriene-3-ol, Phosphor ethanolamine

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References

1. Witola WH, Kwame Matthews, Mark McHugh. In vitro anthelmintic ef?cacy of inhibitors of phosphoethanolamine methyltransferases in Haemonchus contortus. Int J Parasitol Drugs Drug Resist 2016;6:44-53.
2. Prichard RK. Anthelmintic resistance. Veterinary Parasitol 1994;54:259-68.
3. Meena AK, Singh U, Yadav AK, Singh B, Rao MM. Pharmacological and phytochemical evidences for the extracts from plants of the genus vitex–a review. Res 2010;2:1-9.
4. Padmalatha K, Jayaram K, Raju NL, Prasad MV, Arora R. Ethnopharmacological and biotechnological significance of vitex. Bioremediation Biodiversity Bioavailability 2009;3:6-14.
5. Chatterjee A, Prakashi SC. The treatise of Indian medicinal plants. New Delhi: National institute of science communication and information. Resources 1994;10:525.
6. Nair CK, Mohanan N. Medicinal plants of India. New Delhi: NAG Publishersl; 1997. p. 698.
7. Saxena ES, Pant MV, Sharma P. The usual plants of India. CSIR: New Delhi; 1992. p. 683.
8. Sreedhar V, Ravindranath LK, Gopal NM, Sanjithnath M. In vitro antioxidant activity and free radical scavenging potential of roots of vitex trifolia. Res J Pharm Biol Chem Sci 2010;1:1036-44.
9. Anandan R, Jayakar B, Kararn B, Babuji S, Manavalan R, Senthilkumar R. Effect of ethanol extract of flowers of vitex trifolia Linn. on CCL4 induced hepatic injury in rats. Pak J Pharm Sci 2009;22:391-4.
10. Manjunathan BK, Vidya SM, Krishna V, Mankani KL, Singh SD, Manohara YN. Comparative evaluation of wound healing potency of Vitex trifolia L and Vitex altissima L. Phytother Res 2007;21:457-61.
11. Li WX, Cheng-bin C, Cai B, Xin-sheng Y. Labdane-type diterpines as new cell cycle inhibitors and the apoptosis inducers from Vitex trifolia Linn. J Asian Nat Prod Res 2005;7:95-105.
12. Nair AGR, Ramesh P, Subramanian S. Two unusual flavones (artemetin and 7-desmethylartemetin) from the leaves of vitex trifolia. Curr Sci 1975;44:214-6.
13. Pan JG, Xu ZL, Fan JF. GC-MS analysis of essential oils from four vitex species. China J Chinese Mat Med 1989;14:357-9.
14. Ramesh P, Nair AGR, Subramanian SS. Flavone glycosides of vitex trifolia. Fitoterapia 1986;4:282-3.
15. Palavalli LH, Brendza KM, Haakenson W, Cahoon RE, McLaird M, Hicks LM, et al. De?ning the role of phosphomethyl-ethanolamine N-methyl transferase from Caenorhabditis elegans in phosphocholine biosynthesis by biochemical and kinetic analysis. Biochemistry 2006;45:6056-65.
16. Brendza KM, Haakenson W, Cahoon RE, Hicks LM, Palavalli LH, Chiapelli BJ, et al. Phosphoethanolamine-N-methyltransferase (PMT-1) catalyses the ?rst reaction of a new pathway for phosphocholine biosynthesis in Caenorhabditis elegans. Biochem J 2007;404:439-48.
17. Pessi G, Kociubinski G, Mamoun CB. A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methylation. Proc Natl Acad Sci USA 2004;101:6206-11.
18. Pessi G, Choi JY, Reynolds JM, Voelker DR, Mamoun CB. In vivo evidence for the speci?city of Plasmodium falciparum phosphoethanolamine methyltransferase and its coupling to the Kennedy pathway. J Biol Chem 2005;280:12461-6.
19. Witola WH, El Bissati K, Pessi G, Xie C, Roepe PD, Mamoun CB. Disruption of the Plasmodium falciparum PfPMT gene results in a complete loss of phosphatidylcholine biosynthesis via the serine-decarboxylase phosphoethanolamine-methyltransferase pathway and severe growth and survival defects. J Biol Chem 2008;283:27636-43.
20. Murgan M, Mohan VR. Efficacy of different solvent extracts of Vitex trifolia L. and Aristolochia indica L. for potential antibacterial activity. Sci Res Rep 2012;2:110-4.
21. Vigar Z. Atlas of medical parasitology. 2nd Edn. Singapore; PG Publishing House; 1984. p. 216-7.
22. Jha NK, Kumar P. Molecular docking studies for the comparative analysis of different biomolecules to target hypoxia-inducible factor-1α. Int J Appl Pharm 2017;9:83-9.
23. Vijayaraj S, KC Veena. Insilico studies of oxime prodrug of gliclazide against sulphonylurea receptors (SUR 1). Int J Curr Pharm Res 2017;9:100-3.
24. Bauer AW, Kirby WMM, Sherries SC, Turk M. Antibiotic susceptibility of testing by a standard single disc method. Am J Clin Pathol 1966;36:492-6.
25. Thorn GW, Adams RD, Braunwald E, Issalbacher KJ, Petersdorf RG. Harrison’s principles of internal medicine, New York: McGraw Hill Co; 1977. p. 1088-9.
26. Devi K, Indumathy S, Rathinambal V, Uma S, Kavimani S, Balu V. Anthelminthic activity of asta churna. Int J Health Res 2009;2:101-3.
27. Aryal A, S Upreti, K Das. Evaluation of anthelmintic activity of citrus reticulata: in vitro and its phytochemical investigation. Asian J Pharm Clin Res 2017;10:278-80.
28. Danquah CA, Koffuor GA, Annan K, Ketor KC. The antihelminthic activity of Vernonia amygdalina (Asteraceae) and Alstonia boonei de wild (Apocynaceae). J Med Biomed Sci 2012;1:21.
29. Sivashanmugam T, Muthukrishnan S, Umamaheswari M, Asokkumar K, Subhadradevi V, Jagannath P. Discovery of potential cholesterol esterase inhibitors using in silico docking studies. Bangladesh J Pharmacol 2013;8:223-9.
30. Umamaheswari M, Madeswaran A, Asokkumar K, Sivashanmugam AT, Subhadradevi V, Jagannath P. Docking studies: search for possible phytoconstituents for the treatment of gout. Int J Bio Pharm Res 2012;3:6-11.
31. Chaudhary SH, Verma MK, RK Gupta, A Kumar, AN El-shorbagi. Synthesis and investigation of anthelmintic, antibacterial and antifungal activity of 3,3-diphenyl propanamide derivatives. Asian J Pharm Clin Res 2019;12:310-5.
32. Lavanya B, Ramyakrishna PS, Nagarjuna S, Padmanabha YR. In vitro comparative study of anthelmintic activity of Brassica juncea and Brassica oleracea. J Pharm Res 2011;4:2907-9.
33. Chandrashekhar CH, Latha KP, Vagdevi HM, Vaidya VP. Anthelmintic activity of the crude extracts of Ficus racemosa. Int J Green Pharm 2008;2:100-3.
34. Patel J, Kumar GS, Qureshi MS, Jena PK. Anthelmintic activity of ethanolic extract of whole plant of Eupatorium odoratum. Int J Phytomed 2010;2:127-32.
35. Park H, Lee J, Lee S. Critical assessment of the automated AutoDock as a new docking tool for virtual screening. Proteins 2006;65:549-54.
36. Sandeep G, Nagasree KP, Hanisha M, Kumar MMK. AUDocker LE: A GUI for virtual screening with AUTODOCK Vina. BMC Res Notes 2011;4:445-7.
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MUTHUKRISHNAN, S., R. G., and B. S. VARGHESE. “LEAD MOLECULE IDENTIFICATION FROM VITEX TRIFOLIA LINN FOR HELMINTHIASIS USING IN VITRO AND IN SILICO METHODS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 12, no. 2, Jan. 2020, pp. 95-103, doi:10.22159/ijpps.2020v12i2.36353.
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