COMPUTATIONAL STUDY OF BUTYL AND NAPHTHYL AMINE DERIVATIVE OF PERYLENE DIIMIDES TARGETTING TELOMERASE ENZYME FOR ANTICANCER ACTIVITY

Hemalatha Cn; Vijey Aanandhi M

doi:10.22159/ajpcr.2018.v11s4.31679

Authors

Hemalatha Cn Department of Pharmaceutical Chemistry and Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies, Pallavaram, Chennai, Tamil Nadu, India.
Vijey Aanandhi M Department of Pharmaceutical Chemistry and Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies, Pallavaram, Chennai, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2018.v11s4.31679

Keywords:

Butylamine, Naphthyl amine, Perylene derivatives, AutoDock 42, Docking, Discovery studio visualizer 41

Abstract

Objective: Telomeres are protective caps present at the end of the chromosomes and it contains genetic information. From the literature survey, we selected perylene diimides which interact with the telomerase enzyme and possess anticancer activity. Telomestatin a macrocyclic chemical compound that inhibits telomerase activity as well it induces the formation of G-Quadruplex structures in the telomeric region. The main objective of the study was to find the binding affinity of butyl and naphthyl amine derivative of perylene ligands targeting telomerase enzyme for anticancer activity. Telomerase enzyme is responsible for maintaining the length of telomeres and keeping the chromosomes intact longer. Telomeres will become increasingly common with age. Perylene diimides and its derivatives show good biological activity and also in vitro studies possess efficient anticancer agent. The butyl and naphthyl amine derivatives are screened by computational techniques to study regarding binding energy and ligand interactions with respect to the targets.

Methods: Butyl and naphthyl amine derivative of perylene diimides is drawn using Accelrys Draw. The structures are retrieved from the previous study. The structures are converted to pdb formats using Discovery Studio Visualizer 4.1. The study was to investigate the binding energy values of butyl and naphthyl amine derivatives of perylene diimides. Auto Dock 4.2 was used to dock the ligand with the targets. The target selected for docking was 3CE5 and 4B18. The results are visualized by Discovery Studio Visualizer 4.1. The results are compared with the standard drug N,N'-bis-(2-(1- piperidino)ethyl)-3,4,9,10-perylene tetracarboxylic acid diimide (PIPER).

Results: From the results, butylamine derivative of perylene diimide possesses good binding energy when compared with standard drug PIPER. This result shows that the butylamine will be effective for anticancer therapy. In future, in vivo studies of butylamine derivative of perylene diimide will be carried out.

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References

Kazuo S, Konstanty W, Kenichi W, Toshio O, Yuji Y, Kazuo F, et al. Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus. J Am Chem Soc 2001;123:1262-63.

Hemalatha CN, Aanandhi MV. G-quadruplex ligands as stabilizer targeting telomerase as anti-cancer agents. Asian J Pharm Clin Res 2017;10:50-3.

Hemalatha CN, Muthukumar VA. Application of 3D QSAR and docking studies in optimization of perylene diimides as anti-cancer agent. Indian J Pharm Educ Res 2018;52:666-75.

Hemalatha CN, Aanandhi MV. 3D QSAR and Docking study of Perylene-di imides analogues as potent apoptosis inducer and efficacious anticancer agent. Indian

Drugs 2017; 54(12):15-27.

Hemalatha CN, Vijey Aanandhi M. Synthesis of some novel perylene di imides and evaluation of their anti-cancer activity. Asian J Pharm Clin Res 2018;11:1-9.

Available from: https://www.en.wikipedia.org/wiki/AutoDock.

Available from: https://www.rcsb.org/structure/3CE5.

Available from: https://www.rcsb.org/structure/4B18.

Available from: http://www.autodock.scripps.edu/faqs-help/tutorial/using-autodock-with-autodocktools.

Available from: http://www.autodock.scripps.edu/faqs-help/tutorial/using-autodock-with-autodocktools/UsingAutoDock With ADT_v2e.pdf.

Kerwin SM, Chen G, Kern JT, Thomas PW. Perylene di imide G-quadruplex DNA binding selectivity is mediated by ligand aggregation. Bioorg Med Chem Lett 2002;12:447-50.

Ya KS, Wierzba K, Matsuo KI, Ohtani T, Yamada Y, Furihata K, et al. Telomestatin, a novel telomerase inhibitor from Streptomyces annulus. J Am Chem Soc 2001;123:1262-3.

Kim MY, Vankayalapati H, Shin-Ya K, Wierzba K, Hurley LH. Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular G-quadruplex. J Am Chem Soc 2002;124:2098-9.

Barbieri CM, Srinivasan AR, Rzuczek SG, Rice JE, Lavoie EJ, Pilch DS. Defining the mode, energetics and specificity with which a macrocyclic hexaoxazole binds to human telomeric G-quadruplex DNA. Nucleic Acids Res 2007;35:3272-86.

Tera M, Sohtome Y, Ishizuka H, Doi T, Takagi M, Shin-Ya K, et al. Design and synthesis of telomestatin derivatives and their inhibitory activity of telomerase. Heterocycles 2006;69:505-14.

Riou JF, Guittat L, Mailliet P, Laoui A, Renou E, Petitgenet O, et al. Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands. Proc Natl Acad Sci U S A 2002;99:2672-7.

Balijepalli1 MK, Buru AS, Sakirolla R, Pichika MR. Cinnamomum genus: A review on its biological activities. Int J Pharm Pharm Sci 2017;9:1-11.

Putra ED, Haro G, Harahap U, Hutagaol R. In silico screening of hesperetin and naringenin ester derivatives as anticancer against p-glycoprotein. Int J Pharm Pharm Sci 2015;7:485-8.