QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS OF CURCUMIN AND ITS DERIVATIVES AS GST INHIBITORS BASED ON COMPUTATIONAL CHEMISTRY CALCULATION

https://doi.org/10.22146/ijc.21886

Enade Perdana Istyastono(1*), Sudibyo Martono(2), Harno Dwi Pranowo(3), Iqmal Tahir(4)

(1) Lab. Kimia Farmasi, Fakultas Farmasi, Universitas Sanata Dharma, Yogyakarta
(2) Bagian Kimia Farmasi, Fakultas Farmasi, Universitas Gadjah Mada, Yogyakarta
(3) Chemistry Department, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta
(4) Chemistry Department, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author

Abstract


The Quantitative Structure-Activity Relationship (QSAR) study was established on curcumin and its derivatives as glutathione S-transferase(s) (GSTs) inhibitors using atomic net charges as the descriptors. The charges were resulted by semiempirical AM1 and PM3 quantum-chemical calculations using computational chemistry approach. The inhibition activity was expressed as the concentration that gave 50% inhibition of GSTs activity (IC50). The selection of the best QSAR equation models was determined by multiple linear regression analysis. This research was related to the nature of GSTs as multifunctional enzymes, which play an important role in the detoxification of electrophilic compounds, the process of inflammation and the effectivity of anticancer compounds.

The result showed that AM1 semiempirical method gave better descriptor for the construction of QSAR equation model than PM3 did. The best QSAR equation model was described by :

log 1/IC50 = -2,238 - 17,326 qC2' + 1,876 qC4' + 9,200 qC6'

The equation was significant at 95% level with statistical parameters : n = 10, m = 3, r­ = 0,839, SE = 0,254, F = 4,764, F/Ftable = 1,001.


Keywords


QSAR analysis; curcumin; glutathione S-transferase(s) (GSTs); atomic net charge

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References

[1] Lee, K.W., Kwon, S.Y., Hwang, S., Lee, J.U., and Kim, H., 1996, Bull. Korean Chem. Soc., 17, 147-152.

[2] Van der Aar, E. M., Tan, K. T., Commandeur, J. N. M., and Vermeulen N. P. E., 1998, Drug Metab. Rev., 30 (3), 569-643.

[3] Ujihara, M., Tsuchida, S., Satoh, K., Sato, H., and Urade, Y., 1988, Archs. Biochem. Biophys., 264, 428-437.

[4] Sudibyo, M., 2000, Inhibition of glutathione S-transferase by curcumin and its derivatives, Molecular mechanisms and qualitative structure-activity relationships, Ph.D Thesis, Gadjah Mada University, Yogyakarta, Indonesia.

[5] Sudarmanto, B.S.A., 2002, Analisis hubungan kuantitatif struktur-aktivitas seri senyawa analog urkumin sebagai antioksidan menggunakan descriptor berdasarkan perhitungan kimia kuantum, Tesis, Fakultas MIPA, Universitas Gadjah Mada, Yogyakarta.

[6] Nurfina, A., 1994, The synthesis of some symmetrical curcumin derivatives and the study of their anti-inflammatory activities as well as structure-activity relationships, Ph.D. Thesis, Gadjah Mada University, Yogyakarta

[7] Istyastono, E.P., Sudibyo, M., dan Supardjan, A.M., 2003, 2003, Prosiding Seminar Ilmiah Nasional: “Penelitian Farmasi Masa Mendatang Berdasarkan Diversitas Hayati Indonesia”, Fakultas Farmasi, Universitas Sanata Dharma, Yogyakarta.

[8] Clark, A.G., Hamilton, J.F., and Marshall, S.N., 1991, Biochem. J., 278, 193-198.

[9] Istyastono, E.P., Supardjan, A.M., dan Pranowo, H.D., 2003, Majalah Farmasi Indonesia, 14 (3), In Press.

[10] Kubinyi, H., 1993, QSAR : Hansch analysis and related approaches, VCH Verlagsgesellschaft, Weinheim.



DOI: https://doi.org/10.22146/ijc.21886

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Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

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