NOVEL DESIGN OF CALANONE DERIVATIVES AS ANTI-LEUKEMIA COMPOUNDS BASED ON QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS

Leukemia drug discovery based on calanone compound was conducted in previous research and produced 6 calanone derivatives. Most of them have lower activities against leukemia cell L1210 than pure calanone. A Quantitative Structure-Activity Relationship (QSAR) analysis is conducted in this work to find more active calanone derivatives. Six compounds were used as the material of the research because they already have anti-leukemia activity data expressed in Inhibitory Concentration of Fifty Percent Cell Lethal (IC50, in mg/mL). Calculation of predictors was performed by AM1 semiempirical method. QSAR equation is determined using Principle Component Regression (PCR) analysis, with Log IC50 as dependent variable. Independent variables (predictors) are atomic net charges, dipole moment (m), and coefficient partition of n-octanol/water (Log P). This work recommends 3 novel designs of calanone derivatives that may have higher activities (in mg/mL) than those already available, i.e. gemdiol calanone (57.78), 2,4-dinitrophenylhydrazone calanone (30.94) and 2,4,6-trinitrophenylhydrazone calanone (18.96).

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Quantitative Structure-Activity Relationship Analysis of Xanthone Derivates as Cytotoxic Agents in Liver Cancer Cell Line HepG2

Molekul ◽

10.20884/1.jm.2016.11.1.203 ◽

2016 ◽

Vol 11 (1) ◽

pp. 143

Author(s):

Isnatin Miladiyah ◽

Iqmal Tahir ◽

Jumina Jumina ◽

Sofia Mubarika ◽

Mustofa Mustofa

Keyword(s):

Latent Variables ◽

Quantitative Structure Activity Relationship ◽

Structure Activity Relationship ◽

Cytotoxic Agents ◽

Activity Relationship ◽

Log P ◽

Quantitative Structure ◽

Data Set ◽

Relationship Analysis ◽

Structure Activity

The study of xanthone derivatives as cytotoxic agents in cancer is increasing. This study was conducted to explore the Quantitative Structure-Activity Relationship (QSAR) of xanthones as cytotoxic agents in HepG2 cells, to find compounds with better potency. The data set were taken from the previous study, involving 26 xanthone derivates and their cytotoxic activities in Inhibitory Concentration 50% (IC50). The parameters (descriptors) were obtained from quantum mechanics calculation using semiempirical AM1 method and QSAR models determined with principle component regression, with log (1/IC50) as a dependent variable and five latent variables as independent variables. From the 26 main descriptors, PCR reduced them to five latent variables (1st– 5th LV). The QSAR analysis gave the best model as follows: log (1/IC50) = 4.592 – 0.204 LV1 + 0.295 LV2 + 0.028 LV3 (n = 26, r = 0.571, SE = 0.234, Fcount/Ftable ratio = 1.165, PRESS value = 3.766). The study concluded that the descriptors contributed to anticancer activity were volume, mass, surface area, log P, dipole moment, HOMO energy, LUMO energy, and atomic net charge of some atoms. Modifications of substitution that would contribute to cytotoxic activity can be performed at phenyl ring A and C, but not at B.

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

Indonesian Journal of Chemistry ◽

10.22146/ijc.21800 ◽

2010 ◽

Vol 5 (3) ◽

pp. 255-260

Author(s):

Iqmal Tahir ◽

Mudasir Mudasir ◽

Irza Yulistia ◽

Mustofa Mustofa

Keyword(s):

Molecular Orbital ◽

Qsar Model ◽

Quantitative Structure Activity Relationship ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Quantitative Structure ◽

Activity Data ◽

Qsar Analysis ◽

Relationship Analysis ◽

Structure Activity

Quantitative Structure-Activity Relationship (QSAR) analysis of vincadifformine analogs as an antimalarial drug has been conducted using atomic net charges (q), moment dipole (), 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. -0.974.ELUMO +0.515.EHOMO -0.274. +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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