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.ELUMO +0.515.EHOMO -0.274.α +0.029.A -1.673

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


Keywords


QSAR analysis; antimalaria; vincadifformine

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References

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

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