Three-dimensional quantitative structure-farnesyltransferase inhibition analysis for some diaminobenzophenones.
A 3D-QSAR investigation of 95 diaminobenzophenone yeast farnesyltransferase (FT) inhibitors selected from the work of Schlitzer et al. showed that steric, electrostatic, and hydrophobic properties play key roles in the bioactivity of the series. A CoMFA/CoMSIA combined model using the steric and electrostatic fields of CoMFA together with the hydrophobic field of CoMSIA showed significant improvement in prediction compared with the CoMFA steric and electrostatic fields model. The similarity of the 3D-QSAR field maps for yeast FT inhibition activity (from this work) and for antimalarial activity data (from previous work) and the correlation between those activities are discussed.
Xie
Aihua
A
Department of Medicinal Chemistry, University of Mississippi, University, MS, USA.
Clark
Shawna R
SR
Prasanna
Sivaprakasam
S
Doerksen
Robert J
RJ
D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001577:Benzophenones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003959:Diamines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
D000962:Antimalarials; D001577:Benzophenones; D003959:Diamines; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase