Synthesis and Heme Polymerization Inhibitory Activity (HPIA) Assay of Antiplasmodium of (1)-N-(3,4-Dimethoxybenzyl)-1,10-Phenanthrolinium Bromide from Vanillin

https://doi.org/10.22146/ijc.21260

Dhina Fitriastuti(1*), Muhammad Idham Darussalam Mardjan(2), Jumina Jumina(3), Mustofa Mustofa(4)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281
(4) Department of Pharmacology and Toxicology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta 55281
(*) Corresponding Author

Abstract


The synthesis of (1)-N-(3,4-dimethoxy-benzyl)-1,10-phenanthrolinium bromide had been conducted from vanillin. Heme polymerization inhibitory activity assay of the synthesized antiplasmodium has also been carried out. The first step of reaction was methylation of vanillin using dimethylsulfate and NaOH. The mixture was refluxed for 2 h to yield veratraldehyde in the form of light yellow solid (79% yield). Methylation product was reduced using sodium borohydride (NaBH4) with grinding method and yielded veratryl alcohol in the form of yellow liquid (98% yield). Veratryl alcohol was brominated using PBr3 to yield yellowish black liquid (85% yield). The final step was benzylation of 1,10-phenanthroline monohydrate with the synthesized veratryl bromide under reflux condition in acetone for 14 h to afford (1)-N-(3,4-dimethoxy-benzyl)-1,10-phenanthrolinium bromide (84%) as yellow solid with melting point of 166-177 °C. The structures of products were characterized by FT-IR, GC-MS and 1H-NMR spectrometers. The results of heme polymerization inhibitory activity assay of (1)-N-(3,4-dimethoxybenzyl)-1,10-phenanthrolinium bromide showed that it had IC50HPIA of 3.63 mM, while chloroquine had IC50 of4.37 mM. These results indicated that (1)-N-(3,4-dimethoxybenzyl)-1,10-phenanthrolinium bromide was more potential antiplasmodium than chloroquine.

Keywords


vanillin; (1)-N-(3,4-dimethoxybenzyl)-1,10-phenanthrolinium bromide; heme polymerization; antiplasmodium

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References

[1] WHO, 1997, Roll Back Malaria, A Global Partnership, Geneva.

[2] Hadanu, R., Jumina, Anwar, C., Tahir, I., and Mustofa, 2004, Indo. J. Chem., 4 (2), 82–87.

[3] Hadanu, R., Matsjeh, S., Jumina, Mustofa, Widjayanti, M.A., and Sholikhah, E.N., 2007, Synthesis and Antiplasmodial Activity Testing of (1)-N-(4-Methoxybenzyl)-1,10-phenanthrolinium Bromide Compound, Proceeding of ICCS 2007, 24-26 May 2017, Yogyakarta, Indonesia.

[4] Yapi, A.D., Mustofa, Valentin, A., Chavignon, O., Teulade, J.C., Mallie, M., Chapat, J.P., and Blache, Y., 2000, Chem. Pharm. Bull., 48 (12), 1886–1889.

[5] Solikhah, E.N., Supargiyono, Jumina, Wijayanti, M.A., Tahir, I., Hadanu, R., and Mustofa, 2007, J. Trop. Med. Public Health, 37 (6), 1072–1077.

[6] Furniss, B.S., Hannaford, A.J., Smith, P.W.G., and Tatchell, A.R., 1989, Vogel’s Textbook of Practical Organic Chemistry, John Wiley and Sons, New York.

[7] Firdaus, M., Jumina, and Anwar, C., 2008, Indo. J. Chem., 8 (3), 423-425.

[8] Wahyuningsih, T.D., Raharjo, T.J., Tahir, I., and Noegrohati, S., 2002, Indo. J. Chem., 2 (1), 55–63.

[9] Cho, B.T., Kang, S.K., Kim, M.S., Ryu, S.R., and An. D.K., 2006, Tetrahedron, 62 (34), 8164–8168.

[10] Basilico, N., Pagani, E., Monti, D., Olliaro, P., and Taramelli, D., 1998, J. Antimicrob. Chemother., 42 (1), 55–60.

[11] Kumar, S., Guha, M., Choubey, V., Maity, P., Srivastava, K., Puri, S.K., and Bandyopadhyay, U., 2008, Free Radic. Biol. Med., 44 (4), 602–613.

[12] Wood, B.R., Langford, S.J., Cooke, B.M., Glenister, F.K., Lim, J., and Mcnaughton, D., 2003, FEBS Lett., 554 (3), 247–252.

[13] Baelmans, R., Deharo, E., Muñoz, V., Sauvain, M., and Ginsburg, H., 2000, Exp. Parasitol., 96 (4), 243–248.



DOI: https://doi.org/10.22146/ijc.21260

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