Structural characteristics of novel symmetrical diaryl derivatives with nitrogenated functions. Requirements for cytotoxic activity.
In an attempt to discover the essential features that would allow us to explain the differences in cytotoxic activity shown by a series of symmetrical diaryl derivatives with nitrogenated functions, we have studied by molecular modelling techniques the variation in Log P and conformational behaviour, in terms of structural modifications. The Log P data--although they provide few clues concerning the observed variability in activity--suggest that an initial separation of active and inactive compounds is possible based on this parameter. The subsequent study of the conformational behaviour of the compounds, selected according to their Log P values, showed that the active compounds preferentially display an extended conformation and inactive ones are associated with a certain type of folding, with a triangular-type conformation adopted in these cases.
Font
María
M
Sección de Modelización Molecular, Departamento de Química Orgánica y Farmacéutica, University of Navarra, Pamplona, Spain. mfont@unav.es
Ardaiz
Elena
E
Cordeu
Lucia
L
Cubedo
Elena
E
García-Foncillas
Jesús
J
Sanmartin
Carmen
C
Palop
Juan-Antonio
JA
D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000633:toxicity*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry*; D013329:Structure-Activity Relationship
D001555:Benzene Derivatives; D009584:Nitrogen