QSAR Study On Five Kinds Of Coumarin Compounds With Different Biological Activity

Coumarin compounds have a wide range of application value, which have lots ofbiological medicinal activities, including restraining bacteria, anti-HIV virus, loweringblood pressure, anti-osteoporosis, anti-platelet aggregation, analgesic and anti-cancer.What’s more, they have fragrant smell, fluorescence properties and laser performance andso on. So coumarin compounds are widely used in fields of pharmaceuticals, pesticides,fluorescent dyes, stacte and analysis. Through Quantum Structure-Activity Relationship(QSAR) study, the relationship between structure and properties of coumarin compoundscan be found by building QSAR equation, which makes it possible to analyze molecularstructure of medicines to be developed, to predict the performance of new compounds andto design new functional compounds. Therefore, QSAR method can make scientists areobjective to study coumarin compounds owning special properties, which would shortenproduce period and reduce costs.In this paper, the three-dimension structures of target compounds were built by theChem3D Ultra package. And the molecular mechanics MM2force field contained inChem3D Ultra software was applied to search for lower energy conformations for eachmolecule. Basing on the lower energy conformations, the stability configurations withminimum energy of all the target compounds will be optimized with DFT method at thehybrid functional B3LYP and the medium-size basis set6-311G（d，p）(or6-31G（d，p）)level, and all the results were confirmed by frequency analysis.According to different research objects, different structure parameters from thecalculated results were chosen, such as, energy of highest occupied molecular orbital(EHOMO), energy of lowest unoccupied molecular orbital (ELUMO), transition energybetween EHOMOand ELUMO(DELH), total energy(E), dipole moments (μ), molecularstabilization energy(HF), net charge on molecular central, group or atom, and so on. Basison the lowest energy configuration from quantitative calculation, the chemical andphysical parameters of the target compounds were obtained by Hpyerchem software, suchas, logarithm of n-octanol/water partition coefficient (LogP), molar refractivity (MR),molecular polarizability (P), molar volume (V), molecular surface (S) and molecularweight (M), and so on.Finally, the optimum2D-QSAR equation of various series compounds wereconstructed correlation using analysis and regression analysis by mathematical softwareSPSS. The main factors affecting various series target compounds were also discussed.1.25kinds of simple coumarin compounds with inhibition to proteus were studied and their2D-QSAR model was built. The model2D-QSAR shows that transition energy(DELH) and logarithm of n-octanol/water partition coefficient (LogP) are the mainfactors to affect the inhibition activity of target compounds on proteus. Both of them havenegative correlation to inhibition activity of target compounds. Namely the smaller ofDELH and LogP, the stronger of the inhibition activity of the target coumarin compoundsto proteus. The result of NBO analysis of six amino replaced coumarin compoundsdemaonstrated that the active center of these compounds may exist in the atoms N, O10,and O11.2.19polymer coumarin compounds with HIV inhibition were researched and their2D-QSAR model was built. It is identified that molecular Moore refractive index (MR)and molecular molar volume (V) are the main factors affecting their anti-HIV activityfrom the2D-QSAR equation. Both of them have positive correlation to anti-HIVproperties of the target compounds. The bigger of V, the higher activity of the targetcompounds against HIV; and the bigger of MR, the higher activity of the targetcompounds against HIV.3.15triazolylcoumarin compounds with fluorescence performance were studied andthe optimum2D-QSAR equation was constructed. It is demonstrated that the fluorescencequantum generation rate of target compounds has closely relation with triazole ring thecharge QTRIAand molecular surface area S. There is negative correlation between S andfluorescence quantum rate of target compounds, the smaller of S, the higher offluorescence quantum production rate. Instead, there is positive correlation between QTRIAand fluorescence quantum rate, the bigger of QTRIA, the higher of fluorescence quantumgeneration rate.4.2D-QSAR equation of174-(1-Piperazinyl) coumarin compounds with anti-bloodcell condensation in vitro were constructed. By analysis of this equation, it can beconcluded that the extracorporeal anti-platelet condensation activity of target coumarincompounds is related to molecular stability energy (HF) and energy of lowest unoccupiedmolecular orbital (ELUMO), both of which are negative correlation to anti-blood cellcondensation in vitro of target compounds.5.19Heterocyclic coumarin compounds with anti DNA-PK activity were studiedand the optimal2D-QSAR equation was built. It can be concluded that molecular dipolemoment (μ) and molecular molar volume (V) are two important factors affecting antiDNA-PK activity of this series compounds. There is positive correlation between V andinhibition of DNA-PK, while there is negative correlation between μ and inhibition ofDNA-PK.