Synthesis And Antimicrobial Activity Of Cinnamaldehyde Analogues And Their Quantitative Structure-Activity Relationship

Quantitative structure-activity relationship (QSAR) is a model to describe the relationship between the compound structure and its activity. QSAR can help us understand the relationship between molecular structure and biological activity, and explore the interaction law between them. QSAR calculation has been widely applied in the fields of chemistry, environment, medicine and so on. Cinnamaldehyde analogues with a wide range of biological activities have been widely used in medicine, food, feed, wood preservation and other fields. Studying quantitative structure-activity relationship of cinnamaldehyde analogues, acquiring the most important structure information on their bioactivities can guide the design and structural modification of cinnamaldehyde analogues with particular activities. In this work, Ampac and Codessa softwares were used to establish seven quantitative relationship models against three catergories of microbe, involving wood decay fungi, wood mold fungi, and bacteria. Two compounds were designed and synthesized based on the resulting model, and their biological activities were verified. the specific contents of this paper are as follows:(1) Cinnamon oil,p-methoxy cinnamaldehyde and p-chlorocinnamaldehyde were used as the raw materials to react with ethylenediamine, then produce N,N’-bis(trans-cinnamaldehyde)-1,2-diiminoethane, N,N’-bis(p-methoxycinnamaldehyde)-1,2-diiminoethane and N,N’-bis(p-chlorocinnamaldehyde)-1,2-diiminoethane, respectively. The chemical structures of the target compounds were confirmed by FTIR and 1H-NMR.(2) The bioactivities of N,N’-bis(trans-cinnamaldehyde)-1,2-diiminoethane, N,N’-bis(p-methoxy cinnamaldehyde)-1,2-diiminoethane and N,N’-bis(p-chloro cinnamaldehyde)-1,2-diiminoethane against Trametes versicolor, Gloeophyllun trabeum, Aspergillus niger, Paecilomyces lilacinus, Paecilomyces variotii, Staphylococcus aureus, Escherichia coli and Bacillus subtilis were determined. The results showed that all synthesized products had antifungal or antibacterial activity, and their antimicrobial activity increased with the concentration increasing. The antibacterial activity against Staphylococcus aureus was similar between the synthesized products and cinnamaldehyde. The antimicrobial activity of the synthesized products was not as good as cinnamaldehyde against Trametes versicolor, Gloeophyllun trabeum, Aspergillus niger, Paecilomyces lilacinus, Paecilomyces variotii, Escherichia coli and Bacillus subtilis.(3) The chemical structures of the compounds were optimized using Agui 9.2.1 program, and the molecular descriptors of cinnamaldehyde analogues were calculated using the Codessa 2.7.16 program. Then the descriptor numbers were selected by the best multi-linear regression method (BMLR) and a series of models were obtained. Finally, breaking point method was adopted to establish the best quantitative structure-activity relationship (QSAR) models of the bioactivities of cinnamaldehyde analogues against Trametes versicolor, Gloeophyllun trabeum, Aspergillus niger, Paecilomyces lilacinus, Paecilomyces variotii, Staphylococcus aureus, Escherichia coli and Bacillus subtilis, respectively. The models were also satisfactorily validated by internal validation and external validation, and the results showed that R2 is greater than 0.9 in all the models.(4) In order to check the practical ability of cinnamaldehyde analogues on wood protection, indoor wood-protect experiments from rot fungi and molds were conducted referring to the forestry industry standards. The results proved that cinnamaldehyde analogues worked better against Trametes versicolor, Gloeophyllum trabeum, Aspergillus niger and Penicillium citrinum. The molds on wood can be effectively prevented.(5) On the basis of retaining original reactive groups of cinnamaldehyde, methoxycinnamaldehyde-leucine Schiff base and chlorine cinnamaldehyde-leucine Schiff base were synthesized by modification the structure of cinnamaldehyde. Synthetic products were identified by FTIR and 1H-NMR. Filter paper disc method was used to test their bioactivities and they presented great activities against Escherichia coli, Staphylococcus aureus, Aspergillus niger and Penicillium citrinum.The bioactivities of the synthetic products were predicted using the QSAR model established above, and the results were also compared with the experimental values LogAR. The results showed that:the differences were very little between calculated and experimental values of the two compounds against Aspergillus niger and Penicillium citrinum, signifies the model against Aspergillus niger and the one against Penicillium citrinum had better predictive ability. The difference were a little large between calculated and experimental values of the two compounds against Escherichia coli and Staphylococcus aureus, implies the model against Escherichia coli and the one against Staphylococcus aureus had a little low predictive ability.