SYNTHESIS AND ANTIPLASMODIAL ACTIVITY TESTING OF (1)-N-ALKYL- AND (1)-N-BENZYL-6-NITRO-1,10-PHENANTHROLINIUM SALTS AS NEW POTENTIAL ANTIMALARIAL AGENTS

https://doi.org/10.22146/ijc.21356

Ruslin Hadanu(1*), Sabirin Mastjeh(2), Jumina Jumina(3), Mustofa Mustofa(4), Eti Nurwening Sholikhah(5), Mahardika Agus Wijayanti(6)

(1) Department of Chemistry, Faculty of Teachership and Educational Science, Pattimura University, Poka, Ambon
(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
(5) Department of Pharmacology and Toxicology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta 55281
(6) Department of Parasitology, Faculty of Medicine, Universitas Gadjah Mada, Sekip Utara, Yogyakarta
(*) Corresponding Author

Abstract


The synthesis of 5-nitro-1,10-phenanthroline hydrate 2 derivatives from 1,10-phenanthroline monohydrate as starting material has been carried out. The 5-nitro-1,10-phenanthroline hydrate 2 was obtained through nitration reaction using H2SO4 and HNO3 as catalyst and reagent, respectively. Synthesis of (1)-N-alkyl-6-nitro- and (1)-N-benzyl-6-nitro-1,10-phenanthrolinium have been prepared using dimethyl sulphate (DMS), diethyl sulphate (DES), benzyl chloride, benzyl bromine, and benzyl iodide. The reagents of benzyl bromine, and benzyl iodide were synthesized from benzyl chloride using NaBr in ethanol absolute and NaI in acetone, respectively. The five compounds of 5-nitro-1,10-phenanthroline hydrate 2 derivatives were conducted to evaluate the in vitro antiplasmodial activity. The in vitro antiplasmodial was evaluated on strains of Plasmodium falciparum FCR-3 resistant chloroquine and D10 sensitive chloroquine. The 50% inhibition concentration (IC50) of the five compounds ranged from 2.41±1.41 to 0.07±0.01 μM. The results showed that the (1)-N-benzyl-6-nitro-1,10-phenanthrolinium iodide had highest antiplasmodial activity.

Keywords


5-nitro-1,10-phenanthroline hydrate; P. falciparum; antimalarial; antiplasmodial

Full Text:

Full Text PDF


References

[1] Daily, J.P., 2006, J. Clin. Pharmacol., 46, 12, 1487–1497.

[2] Tatu, U., Jain, S., and Priya, P.P., 2005, J. Biosci., 30, 5, 567–571.

[3] Mahmoudi, N., Ortiz, J.V.J., Ciceron, L., Galvez, J., Mazier, D., Danis, M., Derouin, F., and Domenech R.G., 2006, J. Antimicrob. Chemother., 57, 3, 489–497.

[4] Nuri, Dachlan, Y.P., Santosa, M.H., Zaini, N.C., Widyawaruyanti, A., dan Sjafruddin, 2005, Majalah Farmasi Airlangga, 5, 3, 88–90.

[5] Fidock, D.A., Rosenthal, P.J., Croft, S.L., Brun, R., and Nwaka, S., 2004, Nat. Rev. Drug Discovery, 3, 509–520.

[6] Kayembe, J.S., Taba, K.M., Ntumba, K., Tshiongo, M.T.C., and Kazadi, T.K., 2010, J. Med. Plants Res., 4, 11, 991–994.

[7] Olumese, P., 2005, Acta Trop., 95, 265–269.

[8] Yapi, A.D., Mustofa, M., Valentin, A., Chavignon. O., Teulade., J., Mallie, M., Chapat, J., and Blace, Y., 2000, Chem. Pharm. Bull., 48, 12, 1886–1889.

[9] Yapi, A.D., Valentin, A., Chezal, J.M., Chavignon. O., Chaillot, B., Gerhardt, R., Teulade, J.C., and Blace, Y., 2006, Arch. Pharm., 339, 4, 201-206.

[10] Widjayanti, M.A., Solikhah, E.N., Tahir, I., Hadanu, R., Jumina, Supargiono, and Mustofa, 2006, J. Health Sci., 52, 6, 794–799.

[11] Mustofa, M., Yapi, A.D., Valentin, A., Tahir, I., 2003, Berkala Ilmu Kedokteran, 35, 2, 67–64.

[12] Hadanu, R., Mastjeh, S., Jumina, Mustofa, Sholikhah, E.N., Wijayanti, M.A., and Tahir, I., 2007, Indo. J. Chem, 7, 1, 72–77.

[13] Trager, W., and Jensen, J. B., 1976, Science, 193, 4254, 673–675.

[14] Benoit, F., Valentin, A., Pelissier, Y., Marion, C., Dakuyo, Z., Mallie, M., and Bastide, J.M., 1995, Trans. R. Soc. Trop. Med. Hyg., 89, 2, 217–218.

[15] Desjardins, R.E., Canfield, C.J., Haynes, J.D., and Chulay, J.D., 1979, Antimicrob. Agents Chemother., 16, 6, 710–718.



DOI: https://doi.org/10.22146/ijc.21356

Article Metrics

Abstract views : 2488 | views : 2495


Copyright (c) 2012 Indonesian Journal of Chemistry

Creative Commons License
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.

Web Analytics View The Statistics of Indones. J. Chem.