MOLECULAR DOCKING OF ANTITRYPANOSOMAL INHIBITORS FROM EUCALYPTUS TERETICORNIS FOR SLEEPING SICKNESS

AARTHI RASHMI B; HARISHCHANDER A; PRIYANKA K; VASANTH NIRMAL BOSCO

doi:10.22159/ajpcr.2019.v12i9.34632

Authors

AARTHI RASHMI B Department of Bioinformatics, Sri Krishna Arts and Science College, Coimbatore, Tamil Nadu, India.
HARISHCHANDER A Department of Bioinformatics, Sri Krishna Arts and Science College, Coimbatore, Tamil Nadu, India.
PRIYANKA K Department of Bioinformatics, Sri Krishna Arts and Science College, Coimbatore, Tamil Nadu, India.
VASANTH NIRMAL BOSCO Department of Bioinformatics, Sri Krishna Arts and Science College, Coimbatore, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i9.34632

Keywords:

Antitrypanosomal Inhibitors, Eucalyptus tereticornis, Sleeping sickness, Molecular Docking, ADMET studies

Abstract

Objectives: This study aims to investigate the antitrypanosomal inhibitors of Eucalyptus tereticornis for sleeping sickness through molecular docking and studies on Absorption distribution metabolism excursion and toxicology (ADMET).

Methods: In silico molecular docking in ArgusLab software and ADMET analysis in AdmetSAR software was performed for the antitrypanosomal inhibitors of E. tereticornis for sleeping sickness.

Results: Interactions were studied for the ten proteins responsible for sleeping sickness with the 50 antitrypanosomal inhibitors of E. tereticornis. Docking was performed to see the interaction and the best binding energy of compounds with the proteins involved in sleeping sickness. The docking scores were highest for betulonic acid with −15.66 kcal/mol followed by euglobal with −12.24 kcal/mol, B-pinene with −10.313 kcal/mol, A-pinene with −10.3418 kcal/mol, and the least docking score for P-cymene with −10.6045 kcal/mol. Docking results showed that only betulonic acid and euglobal showed that hydrogen bond interaction was as b-pinene, a-pinene, and p-cymene yielded no hydrogen bond interactions so we will be taking the former docking results for further studies. The best docking result was shown by betulonic acid with trypanothione reductase giving binding energy of −15.66 kcal/mol with hydrogen bond interaction of 2.9, so this result was taken for further analysis.

Conclusion: The results of the compound extracted from E. tereticornis will become physiological relevant only when (i) the pure compounds of this plant is available in large quantities; (ii) the Eucalyptus is biochemically stabilized to avoid degradation and enhance absorption in the gastrointestinal tract; and (iii) special delivery methods for this drug to reach the areas of treatment. In this work, the efficacy of E. tereticornis to act against trypanosomal protein was initiated and thus further research in this process would help us to take full advantage of the remedial effects of the compounds extracted from this plant.

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References

Barrett MP, Boykin DW, Brun R, Tidwell RR. Human African trypanosomiasis: Pharmacological re-engagement with a neglected disease. Br J Pharmacol 2017;152:1155-71.

Dawson A, Gibellini F, Sienkiewicz N, Tulloch LB, Fyfe PK. Structure and reactivity of Trypanosoma brucei pteridine reductase: Inhibition by the archetypal antifolate methotrexate. Mol Microbol 2013;61:1457-68.

Gamarro F, Yu PL, Zhao J, Edman U, Greene PJ. Trypansoma brucei dihydrofolate reductase-thymidylate synthase: Gene isolation and expression and characterization of the enzyme. Mol Biochem Parasitol 2017;72:11-22.

Krieger S, Schwarz W, Ariyanayagam MR, Fairlamb AH, Krauth-Siegel RL. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidativex stress. Mol Microbiol 2018;35:542-52.

Mackey ZB, O’Brien TC, Greenbaum DC, Blank RB, McKerrow JH. A cathepsin B-like protease is required for host protein degradation in Trypanosoma brucei. J Biol Chem 2014;279:48426-33.

Pallavi R, Roy N, Nageshan RK, Talukdar P, Pavithra SR. Heat shock protein 90 as a drug target against protozoan infections. Biochemical and evaluation of its inhibitor as a candidate drug. J Biol Chem 2012;285:37964-75.

Lepesheva GI, Park HW, Hargrove TY, Vanhollebeke B, Wawrzak Z. Crystal structures of Trypanosoma brucei sterol 14α-demethylase and implications for selective treatment of human infections. J Biol Chem 2010;285:1773-80.

Parkin DW. Purine-specific nucleoside N-ribohydrolase from Trypanosoma brucei. J Biol Chem 2013;271:21713-9.

Helfert S, Estévez AM, Bakker B, Michels P, Clayton C. Roles of triose-phosphate isomerase and aerobic metabolism in Trypanosoma brucei. Biochem J 2011;357:117-25.

Bosch J, Robien MA, Mehlin C, Boni E, Riechers A. Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma brucei nucleoside 2-deoxyribosyltransferase. J Med Chem 2012;49:5939-46.

Shaw MP, Bond CS, Roper JR, Gourley DG, Ferguson MA. High-resolution crystal structure of Trypanosoma brucei UDP-galactose 4’-epimerase: A potential target for structure-based development of novel trypanocides. Mol Biochem Parasitol 2013;126:173-80.

Harishchander A, Anand DA. Computational approach for identifying therapeutic micro RNAs. Int J Pharm Pharm Sci 2014;6:638-40.

Zumaana R, Saranya S, Rama V. Computational docking and in silico analysis of potential efflux pump inhibitor punigratane. Int J Pharm Pharm Sci 2014;10:27-34.

Anand DA, Harishchander A, Jason UB. An integrated network analysis of psoriasis: A novel approach to disease pathology. Asian J Pharm Clin Res 2015;8:176-8.

Anandaram H, Anand DA. Binding site analysis of micrornas target interaction from genome wide association studies. Asian J Pharm Clin Res 2014;7:121-2.