The Application Of Computer Technologies In The Study Of Structure And Activity Of Natural Products

The structure and activity is key and difficulty of natural product research. Due tothe complex composition of natural products and their structures are difficult todetermine, the status of natural products in drug research has decline. In this paper,some new computer technologies have been introduced to the study of the structureand activity of natural products, which will be powerful tools of natural productresearch.With the development of NMR technologies, identification of planar structure ofnatural product is relatively easy, but the determination of absolute configuration isalways difficult. Studies have shown that the activity of many chiral compounds wasrelated to their absolute configuration. So the research of absolute configuration hasan important role in durg discovery. At present, the methods used to determine theabsolute configuration contain: X-ray single crystal diffraction, Mosher reaction, derivatization, optical rotation, CD and so on. However, these methods have certainlimitations. The method of X-ray single crystal diffraction requires the compound canbe crystallized. The methods of Mosher reaction and derivatization have limitation forthe structures. The methods of optical rotation and CD need the analogue have beenreported. The absolute configuration of many compounds that do not meet theconditions of these menthods also can not been determined. In this paper, I used themethod of quantum chemistry to determine the absolute configuration of compoundswhich can not been determined by the above methods. In the study, I mainly used theGaussion software to calculate the circular dichrosim spectra (ECDS), and opticalrotation values of eight new natural compounds, and determined their absoluteconfiguration by comparison of their calculated and experimental values.Natural products have better activity and less toxicity because their diversitystructure and same evolution with humans. So they are the main resources of drugdiscovery. The efficacies of medical plants have been proved that play their role in thetreatment by the multi-ligent multi-target network. So founding new lead compoundsfrom natural compounds and elaborating the mechanism of medical plants aredifficulty and research focus of natural products research, which is the research areas of modernization of TCM. In this paper, I introduced the forward-docking andreverse-docking technology to natural products research. Founding leadingcompounds though forward-docking is mainly methods of founding leadingcompounds in recent years. However, this method is limited to the synthesiscompound libraries and combinatorial chemistry library due to the lack of largecompound libraries in the filed of natural products. In my research, I have collectedabout4000natural products isolated and identified by our group and built a naturalproduct database by the ISISBase software, which can been used to high-thoughputscreening and virtual screening. A Bcl-2inhibitor was found from the natural productdatabase by virtual screening. This result was verified by the fluorescence polarizationexperiment and SPR experiment and the results showed it had good activity on themolecular level. This compound also exhibited good inbitory activity on the leukemiacells HL-60and K562. In vivo test, it exhibited potent activity at the leukemia nudemice models which were injected K562cells in the right flank.The target of natural products can be predicted by reverse-docking. In this research,this method combines the biotechnology was used to elaborate the mechanism ofmedical plants. The medical plants Daphne odora Thunb. var. marginata,(DOT) andBacopa monnieri (L.) Wettst,(BMW) have the traditional efficacy of trearmentdiabetes. Their active ingredient and relative target was identified by the reversdocking and biological tests in my research. And many active compounds for thistarget had been found by similarity search. This method that computer technologycombined with biology techniques provides a good idears for natural productsresearch.