紫杉醇类似物C_(13)侧链手性构型与活性关系的从头算研究  

Ab initio study on the relationship between chiral conformation of C_(13) side chain and anti-tumor activity in taxol analogues

作　　者：徐志广[1] 许旋[1] 罗一帆[1] 刘海洋[2] 

机构地区：[1]华南师范大学化学系,广东广州510631 [2]华南理工大学化学科学学院,广东广州510640

出　　处：《化学研究与应用》2006年第7期776-780,共5页Chemical Research and Application

基　　金：国家重点基础研究"973计划"项目(G1998051201)资助;广东省科技计划项目(2003C20405)资助

摘　　要：应用从头算RHF/STO-3G方法优化了四个紫杉醚异构体,在RHF/6-31G*水平进行单点计算,并计算了四个分子的静电势。分子立体构型表明:C13侧链上2 R构型的2-OH和3 S构型的3-NH均处于分子外侧,有利于与受体极性基团结合;2 S构型的2-OH和3 R构型的3-NH在分子的内侧,不利于与受体极性基团结合。静电势的结果表明,R构型的2-OH和S构型的3-NH可以产生相应的负电势区域。当C13侧链为天然构型(2 R,3 S)时,分子可能以双基结合的方式通过负静电势区域与受体作用,活性较高。Geometric structures of four taxol analogues were optimized by using ab initio RHF method at STO - 3G level, and their electrostatic potentials were calculated with the same method at 6 -31G ＊ level. Calcularional results show the 2＇ -OH and 3＇ -NH group are positioned out of the molecule in 1 with 2＇R 3＇S conformation, which has the best anti - tumor activity among four analogues. However, the corresponding 2＇ - OH and 3＇ - NH are positioned inner in 2 molecule with 2＇S YR conformation and this analogue has the lowest anti - tumor activity among them. Only one 2＇ - OH or 3＇ - NH group is positioned out of the molecules in 3 and 4, and the anti - tumor activity of 3 and 4 are lover than that of 1. Electrostatic potential calculation indecates the 2＇R - OH and 3＇S - NH group exhibited a negative electrostatic potential. These results suggest 2＇R - OH and 3＇S - NH group in C133 side chain display negative electrostatic potentials and could interact with the receptor via hydrogen bonding. Thus, the 2＇R 3＇S conformarion of taxol analogues possess the best anti - tumor activity.

关 键 词：紫杉醇类似物 手性构型 抗癌活性 从头算 

分 类 号：O641.121[理学—物理化学]