A comparative molecular field analysis of cytotoxic beta-carboline analogs.
OBJECTIVE
To derive a model that could be used in drug design.


METHODS
Beta-carbolines are reported to have antitumor activities on cultured cancer cell lines. A comparative molecular field analysis (CoMFA) was undertaken to elucidate the correlation of cytotoxities and structural parameters of 16 beta-carboline analogs (1-16). The compound 12 was finally used as a template for the other compounds in the dataset because of its highest biological activity.


RESULTS
The CoMFA applied to the final alignment resulted in a q2(cv) of 0.656 and it showed that the steric fields contributed 43.3% of the model information while the electrostatic fields represented the other 56.7%.


CONCLUSIONS
Three designed compounds, which were predicted to have high, moderate and low activities respectively, were synthesized. The IC50 values of these compounds indicated the significance of the analysis in this study. The model derived from the current study could be further used in design for more active compounds.
Hou
Xue-rui
XR
Department of Biochemistry and Center for Biopharmaceutical Research, College of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
Chen
Qi
Q
Cao
Ri-hui
RH
Peng
Wen-lie
WL
Xu
An-long
AL
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002243:Carbolines / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D014407:Tumor Cells, Cultured
C488836:7-methoxy-1-methyl-9-ethyl-pyrido(3,4-b)indole hydrogen chloride; D000970:Antineoplastic Agents; D002243:Carbolines; D007211:Indoles; D011725:Pyridines