关键词: 构效关系, 电子结构, 河豚毒素, 石房蛤毒素, 微分重叠间忽略近似

Tetrodotoxin (TTX) and saxitoxin (STX) are important neurobiological tools because of their selective and high-affinity blockade of the voltage-gated sodium channel of many excitable membranes. In this paper, the semiempirical self-consistent field MO (INDO) calculations have been undertaken for TTX and its analogs. Their active site, way of action and structure-activity relationship have been discussed on the basis of studies of electronic structure and correlative analysis. It is found that the guanidinium group is the most important positive charge center and it may act as an electron acceptor to interact with the most important positive change center and it may act as an electron acceptor to interact with the receptor. Oxygen atoms such as O(17), O(18), O(15), O(21), O(19) are important negative charge sites as electron donor. The comparison between TTX and STX on electronic structural and space structure has been undertaken and it is found that they have similar electronic structural and space structure has been undertaken and it is found that they have similar electronic structural features, moreover, their important active sites are mutually corresponding on space position. Studies of these results show that the sodium channel blockade has common structural features and way of action when interact with the receptor, thus leading to identical biological effect.

Key words: STRUCTURE ACTIVITY RELATIONSHIP, ELECTRONIC STRUCTURE, TETRODOTOXIN, SAXITOXIN, INTERMEDIATE NEGLECT OF DIFFERENTIAL OVERLAP APPROXIMATION (IND