QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR) OF VINCADIFFORMINE ANALOGUES AS THE ANTIPLASMODIAL COMPOUNDS OF THE CHLOROQUINOSENSIBLE STRAIN

Iqmal Tahir; Mudasir Mudasir; Irza Yulistia; Mustofa Mustofa

doi:10.22146/ijc.21800

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR) OF VINCADIFFORMINE ANALOGUES AS THE ANTIPLASMODIAL COMPOUNDS OF THE CHLOROQUINOSENSIBLE STRAIN

https://doi.org/10.22146/ijc.21800

Iqmal Tahir^(1*), Mudasir Mudasir⁽²⁾, Irza Yulistia⁽³⁾, Mustofa Mustofa⁽⁴⁾

(1) Austrian-Indonesian Centre for Computational Chemistry (AIC), Chemistry Department, Faculty of Mathematics and Natural Sciences, Gadjah Mada University, Jogjakarta 55281
(2) Austrian-Indonesian Centre for Computational Chemistry (AIC), Chemistry Department, Faculty of Mathematics and Natural Sciences, Gadjah Mada University, Jogjakarta 55281
(3) Austrian-Indonesian Centre for Computational Chemistry (AIC), Chemistry Department, Faculty of Mathematics and Natural Sciences, Gadjah Mada University, Jogjakarta 55281
(4) Pharmacology Laboratory, Medical Faculty, Universitas Gadjah Mada, Jogjakarta, 55281.
(*) Corresponding Author

Abstract

Quantitative Structure-Activity Relationship (QSAR) analysis of vincadifformine analogs as an antimalarial drug has been conducted using atomic net charges (q), moment dipole (μ), LUMO (Lowest Unoccupied Molecular Orbital) and HOMO (Highest Occupied Molecular Orbital) energies, molecular mass (m) as well as surface area (A) as the predictors to their activity. Data of predictors are obtained from computational chemistry method using semi-empirical molecular orbital AM1 calculation. Antimalarial activities were taken as the activity of the drugs against chloroquine-sensitive Plasmodium falciparum (Nigerian Cell) strain and were presented as the value of ln(1/IC₅₀) where IC₅₀ is an effective concentration inhibiting 50% of the parasite growth. The best QSAR model has been determined by multiple linier regression analysis giving QSAR equation:

Log (1/IC₅₀) = 9.602.qC₁ -17.012.qC₂ +6.084.qC₃ -19.758.qC₅ -6.517.qC₆ +2.746.qC₇ -6.795.qN +6.59.qC₈ -0.190.μ -0.974.E_LUMO +0.515.E_HOMO -0.274.α +0.029.A -1.673

(n = 16; r = 0.995; SD = 0.099; F = 2.682)

Keywords

QSAR analysis; antimalaria; vincadifformine

Full Text:

Full Text PDF

References

[1] Hoffman, S.L., Subramanian, G.M., Collins, F.H., and Venter, J.C., 2002, Nature, 415, 702-709.

[2] Anonim, Surat Kabar Kompas, 27 Januari 2003

[3] Mustofa, 2001, Dissertation Laboratoire d’Immunologie et Parasitologie UFR Sciences Pharmatiques, Montpellier, pp. 103-107

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

[5] Kokpol, S.U., Hannongbua, S.V., Thongrit, N., and Rode, B.M., 1988, Anal. Sci., 4, 565-568.

[6] Rode, B.M., Schwendinger, M.G., Kokpol, S.U., Hannongbua, S.V., and Polman, S., 1989, Monatshefte fur Chemie, 120, 913-921.

[7] Alim, A.H., Pradipta, M.F. dan Tahir, I., 2000, Jurnal Nasional Kimia Fisik, III, 2, 23-26.

[8] Tahir, I., 2000, Analisis Hubungan Kuantitatif Struktur dan Karakter Aroma Senyawa Nitrobenzena, Makalah Seminar Jurnal Nusantara Kimia, Semarang 17 Oktober 2000.

[9] Tahir, I., Setiaji, B. dan Yahya, M.U., 2001, Berkala Ilmiah MIPA, 1, XI, 1-29.

[10] Mudasir, Tahir, I., Yulistia, I., and Rode, B.M., 2003, Quantitative Structure-Activity Relation-ship Analysis (QSAR) of Antimalarial Vinca-difformine Analogues Compounds, Procceding 8^th Scandinavian Symposium on Chemometrics

DOI: https://doi.org/10.22146/ijc.21800