Study On Acaricidal Quantitative Structure Activity Relationships Of Coumarin Compounds Against Tetranychus Cinnabarinus Bois. (Acari:Tetranychidae)

Coumarins, known to widely exist in plants, have various biological activities, which have been widely used not only in medicine, but also in agriculture. Osthole which is one kinds of coumarin compounds not only significantly inhibits the growth of plant pathogenic fungi but also kills some insect pests. Scopoletin have been proven to be antibacterial activity and acaricidal activity. Scoparone and aesculetin also exhibit high antibacterial activity against Botryosphaeria berengeriana f.sp.piricola, Cytospora mandshurica Miura, Coniothyrium diplodiella and Fusarium oxysporum f.sp.vasin-fectum. In particular, our laboratory’ researches have identified that Ca2+-ATPase is the acaricidal target of scopoletin. Accordingly, in this study, we selected 25 coumarin compounds to study their acaricidal activity. The main results are as follows:1. Most of the tested coumarins compounds have a nice acaricidal activity: Acaricidal activity of all the coumarin compounds against Tetranychus cinnabarinus were tested by the method of slide dip, in which most of the coumarins displayed well contact toxicity to the female adults. The compounds of 3-(2-benzimidazolyl)-7-(diethylamino)coumarin,3-(2-benzothiazolyl)-7-(diethylamino)coumarin, 4-Methoxycoumarin and Scoparone showed better acaricidal activity than the control compounds(98.32% spirodiclofen), especially Scoparone, the LC50 values of which reached to 284.8(48h) and 122.2(72h) mg·L-1 respectively.The virulence is equivalent 2.06 and 1.68 times to commercialized acaricide spirodiclofen respectively. Thus, the compound Scoparone of participant with high-efficiency acaricidal active was worth studing, possibily have the potential as an alternative or complement to commodity acaricide for the agriculture manegement.2. Ovicidal activity of tested coumarins are some differences: the corrected mortality of three compounds, treated with 2000 mg·L-1, are greater than 50%. They are 3-(2-benzothiazolyl) 7-(diethylamino) coumarin(2), 4-methoxy coumarin(5) and Scoparone(13) with the corrected mortality of 51.02%, 51.15% and 64.56% respectively. But their ovicidal activity is not better than control agent spirodiclofen(83.74%).3. A model of acaricidal activity has been built by quantitative structure-activity analysis:Frequency analysis has been done to conform the target compounds with minimum energy. All compounds did not appear imaginary frequency, which indicates that the data obtained is reliable and the configuration is stable. 34 kinds of chemical and physical parameters of optimized coumarin compounds have been calculated by Chem3 D with the modules of Calculations-compute properties, Calculations-Gaussian Interface and Hyper Chem, including five categories of electrical resistance, hydrophobicity, geometry, three-dimensional and topology. 17 parameters are selected as described by Pearson correlation analysis to participate in multivariate regression analysis, and then the initial QSAR model is optimized through residual analysis and compound with abnormal mechanism removal. A reliable model has been built with the equation of Y = 4371X1 + 783X2-5X3-726X4-3770, in which equation Stretch-Bend, Dipole-Dipole, the total energy, and Radius are used as independent variable. In this model, the multiple correlation coefficient R is 0.987, the coefficient of determination R2 is 0.973. The results indicates that this model is able to explain 97.3% of the target compound.4. The models of Co MFA and Co MSIA have been built by three-dimensional quantitative structure activity relationship(3D-QSAR): comparative molecular field analysis(Co MFA) was applied to study of 3D-QSAR on coumarins. The reasonable model with predictive ability was obtained from the investigation:q2=0.708, r2=0.98, n=6,steric contour = 63.5%,electrostatic contour = 36.5%. Comparative molecular similarity indices analysis(Co MSIA) was performed based on our acaricidal activities data against T.cinnabarinus. This modal has a good predictive with q2 =0.723, r2=0.96 and n=5, in which the steric contour contributes 20.5%, the electrostatic contour contributes 37.3%, the hydrophobic contour contributes 29.6% and the acceptor contour contributes 12.6%.5. C3, C6 and C7 are important acaricidal active sites of coumarins: In the results of acaricidal activity assay, the coumarins with C3 substituted shows a better acaricidal activity than other compounds, and the coumarins substituted by methoxy at C6 or C7 are also significantly better than the others. In the Co MFA model, it can improve the acaricidal activity that introducing larger volume functional groups at C3, C6 or C7 region of coumarin, but reduce at C4 and C5. In the Co MSIA model, it can improve the acaricidal activity that introducing a hydrophobic functional group at C3 or C7. Additionally, the introduction of hydrogen bond acceptor at C3 will improve the acaricidal activity, but it is not conducive to improving acaricidal activity if introduced hydrogen bond acceptor at C5, C6 or C7.