QUANTITAVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR) OF ANTIMALARIAL 1,10-PHENANTHROLINE DERIVATIVES COMPOUNDS

https://doi.org/10.22146/ijc.21716

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

(1) Department of Chemistry, FKIP, Pattimura University, Poka, Ambon- Indonesia,
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Gadjah Mada University, Sekip Utara, Yogyakarta-Indonesia 55281
(3) Department of Pharmacology and Toxicology, Faculty of Medicine, Gadjah Mada University, Sekip Utara, Yogyakarta-Indonesia 55281
(4) Department of Pharmacology and Toxicology, Faculty of Medicine, Gadjah Mada University, Sekip Utara, Yogyakarta-Indonesia 55281
(5) Department of Parasitology, Faculty of Medicine, Gadjah Mada University, Sekip Utara, Yogyakarta-Indonesia 55281
(6) Austrian-Indonesian Centre for Computational Chemistry, Faculty of Mathematics and Natural Sciences, Gadjah Mada University, Sekip Utara, Yogyakarta, Indonesia 55281
(*) Corresponding Author

Abstract


Quantitative Electronic Structure-Activity Relationship (QSAR) analysis of a series of 1,10-phenanthroline derivatives as antiplasmodial compounds have been conducted using atomic net charges (q), dipole moment (μ) ELUMO, EHOMO, polarizability (α) and log P as the descriptors. The descriptors were obtained from computational chemistry method using semi-empirical PM3. Antiplasmodial activities were taken as the activity of the drugs  against  chloroquine-resistant Plasmodium falciparum FCR3 strain and are presented as the value of ln (1/IC50) where IC50 is an effective concentration inhibiting 50% of the parasite growth. The best model of QSAR model was determine by multiple linear regression method and giving equation of QSAR:

ln 1/IC50  =  3.732 + (5.098) qC5 + (7.051) qC7 + (36.696) qC9 + (41.467) qC11 -(135.497) qC12 + (0.332) μ -

                   (0.170) α + (0.757) log P.

The equation was significant on the 95% level with statistical parameters: n=16; r=0.987; r2= 0.975; SE=0.317;  Fcalc/Ftable = 15.337 and gave the PRESS=0.707. Its means that there were only a relatively few deviations between the experimental and theoretical data of antimalarial activity.


Keywords


QSAR; antimalarial; semi-empirical method; 1,10-phenanthroline

Full Text:

Full Text PDF


References

[1] Breman, J. G. Ame Journal of Tropic and Med and Hyg, 2001, 64, 1.

[2] Mundy, S. B., White, A. C. Jr., Hines, J. S., Marino, B. J. and Young, E. J. Southern Med J, 1996, 89, 616.

[3] Filler, S., Causer, L. M., Newman, R. D., Barber, A. M., Roberts, J. M., MacArthur, J., Parise, M. E. and Steketee, R. W. MMWR Surveillance Summaries, 2003, 52, 1.

[4] Wernsdorfer, W.H., Parasitology Today, 1991, 7, 297 231.

[5] Thiel, W., Adv. Chem. Pyhs., 1996, 93, 703-757

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

[7] Mustofa, Tahir, I., dan Jumina, 2002, Indo. J Chem., 2, 2, 91-96.

[8] Mustofa, Yapii, A.D., Valentin, A., dan Tahir, I., 2003, Berkala Ilmu Kedokteran, 35 (2), 67-74

[9] Sholikhah, E.N., Mustofa, Wijayanti, M.A., Hadanu, R, Tahir, I., Jumina and Supargiyono, 2004, Antiplasmodial Activity and Cytotoxicity of New 1,10-Phenantroline Derivatives, Presented at Third International Eijkman Symposium, Yogyakarta, Indonesia, and September 30– October 3, 2004.

[10] Wijayanti, M.A., Sholikhah, E.N., Tahir, I., Hadanu, R., Jumina, Supargiyono, and Mustofa, 2006, J. Health Science, 52 (6) 794-799.

[11] Leach, A.R., 1996, Molecular Modelling, Principles and Applications, Longman, Singapore.

[12] Dewar, M.J.S., Zoebisch, E.G., Healy, E.F. and Stewart, J.J.P., 1985, J. Am. Chem. Soc., 107, 3902-3909.



DOI: https://doi.org/10.22146/ijc.21716

Article Metrics

Abstract views : 2281 | views : 2274


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.