Structure-activity relationship studies of substituted 17α-acetoxyprogesterone hormones

被引:11
作者
Braga, RS [1 ]
Vendrame, R [1 ]
Galvao, DS [1 ]
机构
[1] Univ Estadual Campinas, Inst Fis Gleb Wataghin, BR-13083970 Campinas, SP, Brazil
来源
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES | 2000年 / 40卷 / 06期
关键词
D O I
10.1021/ci000454f
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Recently a new methodology, called electronic indices methodology (EIM), based on local density of tate calculations (LDOS) using topological and semiempirical methods, was proposed to identify the biological activity of polycyclic aromatic hydrocarbons (PAHs) In this work we apply the concepts of the EIM approach to,classify the progestational activity of 21,17 alpha -acetoxyprogesterones (steroid hormones), (APs). The EIM approach pointed to ra few descriptors, which correctly classify the active/inactive compounds of this class (approximate to 90%). We show that these descriptors arise naturally from principal component analysis (PCA) and neural network (NN) calculations. Moreover, using only the parameters from EIM, instead of a large set of descriptors that have been used before to describe the biological activity of these hormones, we slightly improve and simplify,PCA and NN results. Finally, the molecular region related to the chemical activity of these hormones naturally appears in our theoretical analyis, from the local density of states of the frontier orbitals. This shows the generality of the principles of EIM approach, and confirms that the combination df these distinct methodologies can be an efficient and powerful tool in the structure-activity studies of many classes of compounds.
引用
收藏
页码:1377 / 1385
页数:9
相关论文
共 26 条
[1]   NEURAL NETWORKS APPLIED TO PHARMACEUTICAL PROBLEMS .3. NEURAL NETWORKS APPLIED TO QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP ANALYSIS [J].
AOYAMA, T ;
SUZUKI, Y ;
ICHIKAWA, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (09) :2583-2590
[2]   Theoretical approach to identify carcinogenic activity of polycyclic aromatic hydrocarbons [J].
Barone, PMVB ;
Camilo, A ;
Galvao, DS .
PHYSICAL REVIEW LETTERS, 1996, 77 (06) :1186-1189
[3]   A supersymmetric model for the evolution of the genetic code [J].
Bashford, JD ;
Tsohantjis, I ;
Jarvis, PD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (03) :987-992
[4]  
BRAGA RA, UNPUB
[5]   Identifying carcinogenic activity of methylated polycyclic aromatic hydrocarbons (PAHs) [J].
Braga, RS ;
Barone, PMVB ;
Galvao, DS .
JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 1999, 464 (1-3) :257-266
[6]  
BRAGA SF, UNPUB
[7]  
CARLSTEDTDUKE J, 1988, J BIOL CHEM, V263, P6842
[8]   Structure-activity relationship study of some inhibitors of HIV-1 integrase [J].
Cyrillo, M ;
Galvao, DS .
JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 1999, 464 (1-3) :267-272
[9]  
DUAX WL, 1985, INTERACTION STEROID, P83
[10]   COMPUTER-ASSISTED STRUCTURE-ACTIVITY STUDIES OF CHEMICAL CARCINOGENS - HETEROGENEOUS DATA SET [J].
JURS, PC ;
CHOU, JT ;
YUAN, M .
JOURNAL OF MEDICINAL CHEMISTRY, 1979, 22 (05) :476-483