Molecular Docking of Citronellol, Geraniol and Ester Derivatives as Pim 1 Kinase Inhibitor of Leukemia Cancer

Galuh Widiyarti, Firdayani Firdayani, Muhammad Hanafi, Soleh Kosela, Emil Budianto

Abstract


The proviral insertion site in Moloney murine leukemia virus-1 (Pim1) kinase is overexpressed in many human cancer diseases. Inhibition of Pim1 kinase has been reported can suppress cell proliferation and induce apoptotic cell death, so that the protein could be chosen as drug target for the treatment of cancer. Citronellol and geraniol mainly contained in citronella oil that’s one of Indonesian natural products have bioactivity as antitumor agents, so that both of the compounds can be used as guiding compound to be developed as chemoprevention and chemotherapeutic agent compounds for cancer especially for leukemia cancer. In this research, sixteen citronellol and geraniol esters as an inhibitor of leukemia cancer designed were docked based on their interaction with leukemia receptor target of Pim1 kinase by using Molegro Virtual Docker (MVD). The result showed that the binding citronellol and geraniol esters to Pim1 kinase are more stable and better affinity  than the binding between citronellol and geraniol, indicated by rerank score were lower than rerank score of citronellol/geraniolPim1 kinase. The docking resulted in the four top-ranked compounds, namely, citronellyl caproate, citronellyl caprylate, geranyl caproate and geranyl caprylate with rerank score value from -182.560 to -189.822 KJ/mol. These compounds have hydrogen bonding with amino acid residues of Lys 67 and Asp 186 of an active site of Pim1 kinase. Based on Lipinski’s rule of five, among of the four top-ranked compounds, citronellyl caproate and geranyl caproate were predicted have potency as new chemopreventive and chemotherapeutic agents for leukemia anticancer candidates.


Keywords


Citronellol; geraniol; ester; leukemia anticancer; Pim1kinase

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Arsianti A, Fadilah, Kakiuchi K. 2014. Design and molecular docking study of antimycin A3 analogues as inhibitors of anti-apoptotic BCL-2 of breast cancer. Open J. of Med. Chem. 4: 79-86.

Bayala B, Bassole I, Simpore J. 2014. Anticancer activity of essential oils and their chemical components-a review. Am.J.Cancer Res. 4(6): 591-607.

Bernard S, Christopher P. 2014. WHO: World Cancer Report. IARC Nonserial Publication. 630. WHO Press.

Biblap B, Jhinuk C. 2013. Identification of proapoptopic, anti-inflammatory, anti-proliferative, invasive, and anti-angiogenic targets of essential oils in cardamom by dual reverse virtual screening and binding pose analysis. Asian Pacific Jounal of Cancer Prevention. 14: 3735-3742.

Can BKH, Buchbauer G. 2010. Handbook of Essensial Oil. 56. Printed in the United States of America on acid-free paper.

Cavar S, Maksimovic M. 2012. Antioxidant activity of essensial oil from Palmarosa (Cymbapogon martini). Food Control. 23: 263-267.

Chen W, Viljoen A. 2010. Geraniol-a review of commercial important fragance material. South African J of Botany. 76(4): 643-651.

Christodoulu M, Kontos C, Halabalaki M. 2013. Nature promises new anticancer agents : interplay with the apoptosis-related BCL2 gene family. Anticancer Agent Med.Chem. 13: 1-25.

Cragg GM, Newman DJ. 2013. Natural products as sources of new drug over the last 25 years. J. Nat. Prod. 70: 461-77.

Dykes DJ, Waud WR. 2008. Tumor Models in Cancer Research. 23-40, Humana Press, Totowa, NJ.

Fauser J. 2014. Fatty acids: novel bioactive anti-cancer therapeutics. Anticancer Agent Med.Chem.. 14: 49-65.

Ganjewala D. 2009. Cymbopogon essential oils: chemical compositions and bioactivities. J. Of Essential Oil Therapeutics. 3: 56-65.

Garcia PD, Langowski JL, Wang Y. 2014. Pan-PIM kinase inhibition provides a novel therapy for treating hematologic cancers. Clinical Cancer Research. 30(7): 1834-1845.

Gisele AN, Matthew TB, Wooseok H. 2016. Design, synthesis and structure activity relationship of potent pan-PIM kinase inhibitors derived from the pyridyl carboxamide scaffold. Biorg. Med. Chem. Lett. 26: 2328-2332.

Grassow M, Aparicio C, Carnero A. 2014. The Pim family of Serine/Threonine Kinases in cancer, Med. Research Reviews. 34(1): 136–159.

Hannahan D, Weinberg R. 2010. Lipophilicity in drug discovery. Expert Opin. Drug Disc. 5: 235-248

Khan AQ, Khan R, Qamar W. 2013. Geraniol attenuate12-O-tetradecanoylphorbol-13-acetate (TPA) induced oxidative stress and inflammation in mouse skin: possible role of p38 MAP kinase and NF-xB. Experimental and MolecularPathology. 94(3): 419-429.

Kumar A, Malik F, Bhushan S. 2008. An essential oil and the mayor constituent isointermediol induce apoptosis by increaced expression of mitochondrial cytochrome c and epical death receptors in human leukaemia HL60 cells. Chem.Biol.Interact. 171: 332-347.

Kusumaningrum S, Budianto E, Kosela S, Sumaryono W, Juniarti F. 2014. The molecular docking of 1,4-naphthoquinone derivatives as inhibitors of Polo-like kinase 1 using Molegro Virtual Docker. J.Appl.Pharmaceutic.Scie. 4(11): 47-53.

Li Q, Cheng T, Wang Y. 2011. Drug discovery today. Pub. Chem. Drug Disc. 15(23): 1052-1057.

Lipinski CA, Lombardo F, Dominy BW. 1997. Experimental and computional approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 23. 3-25.

Madnooni M, Mansour K, Gholivand M. 2012. Chemical composition, cytotoxicity and antioxidant activities of the essential oil from the leaves of Citrus aurantium L. African J Biotech.11(2): 498-503.

Mandal S, Bandyopadhyay S, Ghosh MK. 2012. Natural products: promising resources for cancer drug discover. Anticancer Agent Med.Chem. 12: 49-75.

Matthew TB, Gisele N, Wooseok H. 2015. Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-ifluorophenyl)-5-fluoropicolinamide (PIM447), a potent and selective proviral insertion site of Moloney Murine Leukemia (PIM) 1, 2, and 3 kinase inhibitor in clinical trials for hematological malignancies. J. Med.Chem. 58: 8373-8378.

Merkel AL, Meggers E, Ocke M. 2012. Pim1 kinase as a target for cance. Early Online Expert Opin. Investig. Drugs. 1-12.

Narayanan A, Baskaran SA, Amalaradjon M. 2015. Anticarcinogenic properties of medium chain fatty acids on human colonrectal, skin, and breast cancer cells in vitro. Int. J. Mol. Sci. 16: 5014-5027.

Qurishi Y, Hamid A, Majeed R. 2011. Interaction of natural products with cell survival and signaling pathways in the biochemical elucidation of drug targets in cancer. Future Oncol. 7( 8): 1007-1021.

Raut JS, Karuppayil SM. 2014. A Status review on the medicinal properties of essential oil. Ind. Crops. Prod. 62: 250-264.

Ravi S, Sureshkumar C and Dhivya S. 2012. Design, synthesis, and evaluation of Geraniol esters against the inflammation drug target protein TNF-. Int. J. of Curr. Res. 4(9): 40-44.

Sharma P, Mondhe D, Muthiah S. 2009. Anticancer activity of an essential oil from Cymbopogan flexuosus. Chem. Biol. Interact. 179. 2(3): 160-168.

Siswandono. 2015. Rancangan Obat Rasional dan Pemodelan Molekul, Kuliah Umum Kimia Medisinal. 1-62, Labtiap BPPT, Puspiptek Serpong.

Tursynbay Y, Zhang J, Li Z. 2016. Pim-1 kinase as cancer drug target: an update Review. Biomed. Report. 4: 140-146.

Weirauch U, Beckmann N, Thomas M. 2013. Functional Role and Therapeutic Potential of The Pim1 Kinase in Colon Carcinoma. Neoplasia. 15 (7): 783-794.

Widiyarti G, Hanafi M, Kosela S, Budianto E. 2016. Cytotoxic activity of cytronellyl caproate on Murine Leukemia (P388) Cells. Int. J. App. Chem. 12(3): 209-220.

Yanuar A. 2012. Penambatan Molekul, Praktek dan Aplikasi pada Virtual Screening. Fakultas Farmasi Universitas Indonesia.




DOI: https://doi.org/10.15408/jkv.v5i2.7195 Abstract - 0 PDF - 0

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