SEARCH FOR GLIOMA DIRECT BINDING SITE OF ALKALOID USING PROTEIN-LIGAND ANT SYSTEMÂ®
Objective: This research aims to know the best affinity and the best chemical conformation of anticancer compounds from alkaloid groups that have closed direction to Glioma-associated oncogene using protein-ligand ant system (PLANTSÂ®). The interaction energy and hydrogen bond are included as evaluated targets.
Methods: In this research, 27 ligands with root mean square deviation score at 1.614 Ã… and cyclopamine as native ligand are used. Meanwhile, staurosporinone acts as gliomas directed-binding-site-internal-control. Each ligand is docked in GLI with Protein Data Bank code 2GLI using two methods, GLI contains water and without water.
Results: PLANTSÂ® score for native ligand in the first and the second method is âˆ’73.9002 and âˆ’73.2700, respectively. Pancracristine, homoharringtonine, and sanguinarine showed PLANTSÂ® score closed to the cyclopamine score result, but their hydrogen bond interaction differed from native ligan interaction. Evodiamine ligand has a good score and hydrogen bond to the same amino acid of protein GLI, which are GLU 175 and THR 173. This result indicated that evodiamine has the same identical mechanism as staurosporinone.
Conclusion: The evodiamine is determined to have the same working mechanism as a GLI inhibitor.
2. Rifai Y, Tani HB, Nur M, Aswad M, Lallo S, Wahyudin E. Synthesis, molecular mechanism and pharmacokinetic studies of new epoxy lignan-based derivatives. Arch Pharm 2016;349:848-52.
3. Evangelista M, Tian H, Sauvage FJ. The hedgehog signaling pathway in cancer. Clin Cancer Res 2006;12:5924-5.
4. Kroemer RT. Molecular modelling probes: Docking and scoring. Biochem Soc Trans 2003;31:980-4.
5. Leach AR, Shoichet BK, Peishoff CE. Docking and scoring, perspective: Prediction of protein-ligan interactions. Docking and scoring: Success and gaps. J Med Chem 2006;49:5851-5.
6. Marie CL, Michael J, Rachid S, Jackies F, Michele S, Francois M, et al. Hepatoprotective and antiinflammatory effects of a traditional medicinal plant of chile, Peumeus Boldus. Planta Med 1991;49:110-5.
7. Jiang J, Hu C. Evodiamine: A novel anti-cancer alkaloid from Evodia rutaecarpa. Molecules 2009;14:1852-6.
8. Kumar D, Rawat DS. Marine natural alkaloids as anticancer agents. Res Signpost 2011;37:213-68.
9. Shoeb M. Anticancer agents form medicinal plants. Bangladesh J Phamacol 2006;2:35-40.
10. Ying-Yue Z, Xue-Shi H, De-Quan Y, Shi-Shan Y. Antitumor alkaloids isolated from Tylophora ovate. Acta Botanica Sinica 2002;44:349-53.
11. Padmanabha BV, Chandrashekar M, Ramesha BT, Gowda HC, Gunaga RP, Suhas S, et al. Patterns of accumulation of camptothecin, an anti-cancer alkaloid in Nothapodytes nimmoniana graham, in the Western Ghats, India: Implications for identifying high-yielding sources of the alkaloid. Curr Sci 2006;90:95-100.
12. Powel RG, Rogovin SP Jr., Smith CR. Isolation of antitumor alkalois from Cephalotaxus harringtonia. Ind Eng Chem Prod Res Develop 1974;13:129-32.
13. Lucio AS, Almeida JR, Barbosa-Filho JM, Pita JC, Branco MV, Diniz MF, et al. Azaphenanthrene alkaloids with antitumoral activity from Anaxagorea dolichocarpa sprague and sandwith (Annonaceae). Molecules 2011;16:7125-31.
14. Ingrassia L, Lefranc F, Mathieu V, Darro F, Kiss R. Amarylldaceae isocarbostyril alkaloids and their derivates as promosing antitumor agents. Trans Oncl 2008;1:1-13.
15. Liu XS, Jiang J, Jiao XY, Wu YE, Lin JH, Cai YM. Lycorine induces apoptosis and down-regulation of mcl-1 in human. Cancer Lett 2009;274:16-23.
16. Kaur R, Singh J, Singh G, Kaur H. Anticancer plants a review. J Nat Prod Plant Resour 2011;1:131-6.
17. Mahindroo N, Punchihewa C, Fujii N. Hedgehog-gli signaling pathway inhibitors as anticancer agents. J Med Chem 2009;52:3829-45.
18. Murlidhar M, Goswami TK. Piper nigrum and piperine: An update. Phytother Res 2013;27:1121-30