* Corresponding Author
SYNTHESIS AND ANTIPLASMODIAL ACTIVITY TESTING OF (1)-N-(4-METHOXYBENZYL)-1,10-PHENANTHROLINIUM BROMIDE
https://doi.org/10.22146/ijc.21698 Ruslin Hadanu(1*), Sabirin Mastjeh(2), Jumina Jumina(3), Mustofa Mustofa(4), Mahardika Agus Widjayanti(5), Eti Nurwening Sholikhah(6)
(1) Department of Chemistry, Pattimura University, Ambon, Indonesia
(2) Laboratorium of Organic Chemistry, Department of Chemistry, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281.
(3) Laboratorium of Organic Chemistry, Department of Chemistry, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281.
(4) Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281.
(5) Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281.
(6) Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia 55281.
(*) Corresponding Author
Abstract
Synthesis of (1)-N-(4-methoxybenzyl)-1,10-phenanthroline bromide from 1,10-phenanthroline monohydrate and 4-methoxybenzaldehyde as starting material and evaluation of its antiplasmodial activities have been carried out. The 4-methoxybenzyl alcohol was prepared from 4-methoxy-benzaldehyde using sodium borohydride (NaBH4) reagent and ethanol absolute solution. The mixture was refluxed for 3 h. To yield colorless dilution compound with 90.41 % in efficiency. Furthermore, bromination of 4-methoxybenzyl alcohol with phosphorus bromide (PBr3) was conducted by refluxing for 3 h. The product of this reaction was yellow liquid of 4-methoxybenzyl bromide, 79.03% yield and 95.34 % purity. The final step of reaction was benzylation of 1,10-phenanthroline monohydrate with 4-methoxybenzyl bromide reagent. It was conducted by refluxing in aceton for 8 h at 55 oC. The yield of the reaction was (1)-N-(4-methoxybenzyl)-1,10-phenanthroline bromide (77.63%). It is pink solid form, and its melting point is 192-193 oC. Identification of the product was carried out by means of GC-MS, IR and 1H-NMR spectrometers. The in vitro antiplasmodial activity on chloroquine-resistant Plasmodium falciparum FCR-3 strain and chloroquine sensitive P. falciparum D10 strain for (1)-N-(4-methoxybenzyl)-1,10-phenanthroline bromide were determined by microscopic method. The result showed that after 72 h incubation, it has IC50 0.93±0.02 µM and 1.21±0.09 µM, respectively.
Keywords
Full Text:
Full Text PDFReferences
[1] Robbert, A., Vical, F.A., Cabaret, O.D., and Meunier, B., 2001, Pure Appl. Chem., 73, (7): 1173-118.
[2] Baird, J.K., Widay, I., Fryauff, D.J., Sutanihardja, M.A., Leksana, B., Widjaya, H., Kysdarmanto, and Subianto, B., 1997, Am J Trop Med Hyg, 56: 627-631.
[3] Basco, L. K., Ruggeri, C., and Le Bras, J., 1994, Molecules Antipaladiques: Relations Structure-Activity, ed Masson, 108-234.
[4] Rang, H.P., Dale, M.M., Ritter J.M., and Moore P.K., 2003, Pharmacology, 5thed, Edinburgh: Churchill Livingstone.
[5] Karbwang, J., and Na-Banchang, K., 1991, Clin Phamacokinet, 27: 104-109.
[6] Bassi, P.U., Buratai, B.I., and Kuchali, W., 2006, AJBR, 9: 31-35.
[7] Yapi, A.D., Mustofa, M., Valentin A., Chavignon O., Teulade, J., Mallie, M., Chapat, J., and Blace, Y., 2000, Chem. Pharm. Bull., 48: 1886-1889.
[8] Mustofa, M., Yapi, A. D., Valentin, A., and Tahir, I., 2003, J Med Sci., 35: 67-74.
[9] Hadanu, R., 2004, Syntesis of antimalarial (1)-N-alkyl-1,10-phenanthrolinium and 3-(2-hydroxy-ethyl)-2-methyl-1,10-phenanthroline-4-ol, Thesis, Gadjah Madah University, Yogyakarta.
[10] Hadanu, R., Anwar C., Jumina, and Mustofa, 2005, Journal Science and Sibernatika, 18 (3): 297-307.
[11] Supargiyono, Jumina, and Mustofa, 2005, New antimalarial of (1)-N-benzil-1,10-phenanthroline: Synthesis, antiplasmodial activity, toxicity, phamacokinetic, action mechanism and their formula. Research Report of Post Graduate Research Grant. Jakarta: Minister of Education Indonesian Goverment.
[12] Mustofa, Jumina, Wijayanti M.A., Tahir, I., and Sholikhah, E.N., 2005, Development of New Compounds of 1,10-phenanthroline Derivatives as Antimalarial Drug, Researh Report of 10th Competitive Integrated Research. Jakarta: Minister of Research and Technology Indonesian Goverment.
[13] Hadanu, R., Matsjeh S., Jumina, Mustofa, Wijayanti M.A., and Sholikhah E.N., 2006, Synthesis of antimalarial compound (1)-N-(4-ethoxybenzyl)-1,10-phenanthrolinium chloride, Proceding of Seminar and Congress Association Chemist of Indonesian, Jakarta.
[14] Hadanu, R., Matsjeh S., Jumina, Mustofa, Wijayanti M.A., and Sholikhah E.N., 2006, Synthesis Of Antimalarial Drug (1)-N-(4-ethoxybenzyl)-1,10-phenanthrolinium Bromide, Proceding of International Seminar on Department of Chemistry, Gadjah Mada University, Yogyakarta.
[15] Hadanu, R., Matsjeh S., Jumina, Mustofa, Wijayanti M.A., and Sholikhah E.N., 2006c, Synthesis of (1)-N-(4-benzyloxy-3-methoxy-benzyl)-1,10-phenanthrolinium chloride as Antimalarial, Proceding of Claster Scince-Technology Seminar, Gadjah Madah University, Yogyakarta.
[16] Wijayanti, M.A., Sholikhah, E.N., Tahir, I, Hadanu, R., Jumina, Supargiyono, and Mustofa, 2006, J Health of Sci, 52 (6): 794-799.
[17] Sholikhah, E.N., Supargiyono, Jumina, Wijayanti, M.A., Tahir, I, Hadanu, R., and Mustofa, 2006, Southeast Asian J Trop Med Public Health, 37 (6): 072-1077.
[18] Trager, W., and Jensen, J.B., 1976, Science, 193: 673-675.
[19] Benoit, F., Valentin, A., Pellisier, Y., Marion C., and Dakuyo, Z., 1995, Trans Roy. Soc. Trop. Med. Hyg., 89: 217-218.
DOI: https://doi.org/10.22146/ijc.21698
Article Metrics
Abstract views : 1383
| 
views : 1419
Copyright (c) 2010 Indonesian Journal of Chemistry
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.