QSAR STUDY OF 1,10-PHENANTHROLINE DERIVATIVES AS THE ANTIMALARIAL COMPOUNDS USING ELECTRONIC DESCRIPTORS BASED ON SEMIEMPIRICAL AM1 CALCULATION

https://doi.org/10.22146/ijc.21919

Mustofa Mustofa(1*), Iqmal Tahir(2), Jumina Jumina(3)

(1) Laboratorium Farmakologi & Toksikologi/Pusat Kedokteran Tropis, Fakultas Kedokteran UGM
(2) Pusat Kimia Komputasi Indonesia Austria Jurusan Kimia Fakultas MIPA UGM Jogjakarta
(3) Pusat Kimia Komputasi Indonesia Austria Jurusan Kimia Fakultas MIPA UGM Jogjakarta
(*) Corresponding Author

Abstract


Quantitative Structure-Activity Relationship (QSAR) analysis of 1,10-phenantroline analogs as antimalarial drug has been conducted using atomic net charges (q) as predictors of their activity. Data of predictors are obtained from computational chemistry method using semi-empirical molecular orbital AM1 calculation. Antimalarial activities are taken as the activity of the drugs against plasmodium falciparum (FcM29-Cameroun) strain and are presented as the value of ln(1/IC50) where IC50 is an effective concentration inhibiting 50 % of the parasite growth.  The results show that there is correlation between antiplasmodial activity and electronic structure as represented by a linear function of activity versus atomic net charges of N1, C7, C10, C14 atoms on the 1,10-phenanthroline skeleton and is expressed by :

log IC50 = -3,4398 - 14,9050 qN1 - 8,5589 qC10 - 14,7565 qC7 + 5,0457 qC11

The equation is significant at 95% level with statistical parameters : n = 13; r = 0,96275; r2 = 0,92689; SE = 0,61578 and F (4,8) = 25,3556.


Keywords


antimalarial drug; 1,10-phenanthroline; QSAR; antiplasmodial activity

Full Text:

Full Text Pdf


References

[1] Vial, H., and Ancelin, M. L., 1994, Pathol. Biol., 42, 138-144.

[2] Falade, C. O., Salaka, L. A., Sowunmi, A., Oduola, A. M., and Larcier, P., 1997, Trans. R. Soc. Trop. Med. Hyg. 91(1), 58-62.

[3] Pradines, B., Mabika Mamfoumbi, M., Parzy, D., Owono Medang, M., Lebeau, C., Mourou Mbina, J. R., Doury, J. C., and Kombila, M., 1998, Parasitology, 117, 541 – 545.

[4] Humberstone, A. J., Porter, C. J., and Charman, W. N., 1996, J. Pharm. Sci., 85(5), 525 – 529.

[5] Sowunmi, A., Falade, C. O., Oduola, A. M., Ogundahunsi, O. A., Fehintola, F. A., Gbotosho, G. O., Larcier, P., and Salako, L. A., 1998, Trans. R. Soc. Trop. Med. Hyg., 92(4), 446 – 448.

[6] 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.

[7] Mustofa, 2000, In Vitro and In Vivo Activity of the Divers of Natural and Synthetic Antimalarial : Effect of Potentialisator and The Possibility of Mechanism of Actions. Disertasi, University of Montpellier I, France.

[8] Vinter, J. G. & Gardner, M, 1994, Molecular Modeling and Drug Design, The Macmillan Press Ltd., Houndmills.

[9] Leach, A. R, 1996, Molecular Modelling : Principles and Application, Addison Wesley Longman Limited, Singapore.

[10] Dewar, M. J. S., Zoebisch, E. G., Healy, E. F., and Stewart, J. J. P., 1985, J. Am. Chem. Soc., 10, 3902-3909.

[11] Wallace, R. J., and McKain, N, 1996, J. Appl. Bacteriol, 81(1), 42 - 47.

[12] Wallace, R. J., Newbold, C. J., and McKain, N., 1996, J. Appl. Bacteriol, 80, 425-430.



DOI: https://doi.org/10.22146/ijc.21919

Article Metrics

Abstract views : 6714 | views : 4217


Copyright (c) 2010 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.