含硫芳香族化合物发光菌毒性的3D—QSAR研究

利用比较分子力场分析法（CoMFA)与比较分子相似指数分析法（COMSIA）研究了29种含硫芳香族化合物对发光菌的急性毒性与其结构间的三维构效关系（3D－QSAR），得到了具有较强预测能力的3D－QSAR模型，并在此基础上剖析了这批含硫芳香族化合物结构与活性之间的内在关系，深入探讨化合物的毒性作用机理。

3D-QSAR Study on Aromatic Sulfur-Containing Compounds

The quantitative relationships among the structures of 29 aromatic sulfur-containing compounds and their toxicity to photobacterium Phosphoreum were investigated by 3D-QSAR techniques of Comparative Molecular Field Analysis (CoMFA) method and Comparative Molecular Similarity Index Analysis (CoMSIA), while several models with considerable predictive abilities were obtained. It could be seen obviously that the toxicity was as the following order according to the substituents: dinitrophenyl > chloronitrophenyl >nitrophenyl. Moreover, the toxicities were associated with the position of the substituents. For example, 1,4- or 4- substituted compounds were more toxic than the 2- substituted ones. Besides, more information about these compounds could be seen from the three-dimensional contour maps. The CoMSIA model implied the hydrogen bond donor traits and hydrophobic requirements for recognition forces of the receptor site, while the steric and electrostatic characteristics of these compounds could be explored from CoMFA models. Furthermore, with the complementation of traditional 2D-QSAR analyses, a further understanding of the toxicity mechanism for these aromatic sulfur-containing compounds could be obtained. The formation of hydrogen bond between FMNH 2, the reduced state of coenzyme and the molecule of aromatic sulfur-containing compounds might be the possible reason for the decrease of normal luminescence of photobacterium Phosphoreum.