用分子轨道法对倍半萜类抗癌剂构效关系的研究

本文列举35种倍半萜类抗癌剂的结构和活性,从中归纳出有强抗癌活性的必要条件是分子中必须具有含共轭π键的活性基团。采用CNDO分子轨道法模拟地计算了这些活性基团的E_LUMO,发现其E_LUMO愈低,其母体的抗癌活性就愈高,并且这些E_LUMO与RNA、DNA分子中碱基的E_LUMO的差值较小。作者据此提出了倍半萜类抗癌剂的两个亲电活性基团分别与RNA或DNA的双股核苷酸链上的碱基发生电荷转移络合的抗癌机理。

Structure-activity relationships of sesquiterpenoid antitumor agents using molecular orbital method

The structures and activities of 35 sesquiterpenoid antitumor agents are discussed, and found that each compound must have an active group with a conjugated π-bond. The values of their E_LUMO are imitatively calculated using CNDO method. It is evident that the smaller the value of the E_LUMO, the more active the original antitumor compounds, The differences between the values Of E_LUMO of the bases in DNA (and in RNA) and those of E_LUMO of the imitative sesquiterpenoids are so small that the charge can be transferred between them. It is postulated that this charge transfer complexing between the two electrophilic groups in sesquiterpenoids and the bases in double helix of DNA or/and RNA may contribute to the antitumor mechanism of this class of compounds.