STRUCTURE ACTIVITY RELATIONSHIP OF CA-2+ CHANNEL BLOCKERS - A STUDY USING CONFORMATIONAL-ANALYSIS AND CHEMOMETRIC METHODS

被引:5
作者
BELVISI, L
BROSSA, S
SALIMBENI, A
SCOLASTICO, C
TODESCHINI, R
机构
[1] CTR CNR,DIPARTIMENTO CHIM ORGAN & IND,VIA VENEZIAN 21,I-20133 MILAN,ITALY
[2] IST LUSOFARM ITALIA SPA,I-20132 MILAN,ITALY
[3] DIPARTIMENTO CHIM FIS & ELETTROCHIM,I-20133 MILAN,ITALY
关键词
CALCIUM CHANNEL BLOCKERS; CONFORMATIONAL ANALYSIS; PRINCIPAL COMPONENT ANALYSIS; CHEMOMETRIC METHODS; PHARMACOPHORE IDENTIFICATION;
D O I
10.1007/BF00135315
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A structure-activity relationship study has been done on 8 compounds with the activity known as 'Ca2+ channel blockers'. Conformational analysis was carried out using a molecular mechanics method. The 3D-QSAR approach was used and the most polar functional groups present in all the molecules were considered. Eight interatomic distances are necessary to define the relative spatial disposition of these relevant molecular fragments. The structure activity relationship between interatomic distances and biological activity was performed using statistic and chemometric methods. In particular. with Principal Component Analysis, it was possible to reduce the number of interatomic distances: only six of the eight distances are sufficient to describe the system in a useful way. A classification method was iteratively used to select the most probable conformations linked to the biological activity and to build a model able to classify conformations according to their biological behaviour. Cluster analysis on the active selected conformations subsequently allowed the identification of two different geometrical patterns for the active compounds. Finally the validity of the model was verified by correctly predicting the activity of other molecules not used in the construction of the model but possessing known activity.
引用
收藏
页码:571 / 584
页数:14
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