Molecular Modeling of Anti-Microbacterial Agent by QSAR Study of Diiodocoumarin Derivatives

Abstract

Coumarins and their derivatives have biological activities such as anti-microbial, anticancer, antioxidant and anti-HIV properties. Molecular modeling using Quantitative Structure and Activity Relationship (QSAR) has been performed on a series of diiodocoumarin derivatives as effective antimicrobial agent. This research focus on a set of experimetally inhibition-zone diameter (mm/mg sample) value data of 5diiodocoumarin derivatives, that is 6,8-diiodocoumarin-3-carboxylate, 6,8-diiodocoumarin-3-carboxylic acid, 6,8-diiodocoumarin-3-carbonylchloride, N-(4-(2-Hydroxyethyl)phenyl)-6,8-diiodocoumarin-3-carboxamide, and N-(4-Hydroxyphenyl)-6,8-diiodocoumarin-3-carboxamide. The mathematical method multi linear regression calculation was used to build the QSAR model. QSAR analysis was employed on fitting subset using log (1/inhibition-zone diameter) as dependent variable and atomic net charges, dipole moment and partition coefficient in n-octanol/water as independent variables. The parameterized Model number 3 (PM3) method was carried out to calculate the quantum chemical descriptors, chosen to represent the electronic descriptors of molecular structures. The relationship between log (1/inhibition-zone diameter) and the descriptors was described by resulted QSAR model. The resulted QSAR model for caffeic acid derivatives as anti-microbial is presented below: 8.051+32.24C5+27.24O7+0.021logPR=1;R2=0.999;SE=0.008;Sig=0.038 QSAR model for diiodocoumarin derivatives showed partition coefficient of n-octanol/water and atom charge in C5 and O7 gave significant effect as descriptors to the anti-microbial activity.N-(4-(2-Hydroxyethyl)phenyl)-6,8-diiodocoumarin-3carboxamide and N-(4-Hydroxyphenyl)-6,8-diiodocoumarin-3-carboxamide have higher anti-microbial activity because the presence of hydroxyphenylgroup increases the electron density value of O7 and C5. The calculated PRESS (Predicted Residual Error Sum of Square) value was 7.13E-05 which indicates the calculated log (1/inhibition-zone diameter) using QSAR Hansch Model of diiodocoumarinderivativesis similar with experimental data.