Artemisinin Derivatives, Quantum Chemistry And Structure-activity Relationship Study

Artemisinin was first isolated from Artemisia annuaL. by Chinese scientists in 1972. It is an effective antimalarial drug against malaria at present. Due to its high efficiency, rapid action and low toxicity for treating malarial, it has attracted worldwide attention. But artemisinin hardly dissolves in the aqueous solution, which leads to low bioavailability. Furthermore, the drug has a short half-life and the recrudescences are common. The quantum chemistry and quantitative structure-activity relationships study on drugs is an important means to develop new generation drugs. The purpose of our thesis is to find a good structure-activity relationship on the level of microcosmic structure by means of quantum chemistry, molecular mechanics and statistical analysis methods so as to provide some useful information for develop new antimalarial drugs with improved efficiency and stability.Compared with some current computational methods, the advanced density functional theory was employed to calculate the electronic structure of artemisinin and desoxyartemisinin in the thesis. The results of calculation prove theoretically that the endoperoxy bridge is essential for antimalarial activity. The theoretical study on nine artemisinin analogs illustrates A, C and D ring and non-endoperoxy oxygen atoms in the compounds are not important for antimalarial activity. B ring having endoperoxy bridge has played an important role. The dipole moment, AE and orbital composition of HOMO have good correlation with antimalarial activity. The results obtained may be helpful in synthesizing more simple, potent artemsinin derivatives.The quantum parameters of thirty-five 10-O substituted artemisinin derivatives were calculated by B3LYP/6-31G* method. The quantum indices and topological indices were extracted based on artemisinin derivatives' electronic structure. The comparatively significant QSAR models were built and have predictive ability.