Synthesis and comparative molecular field analysis (CoMFA) of argentatin B derivatives as growth inhibitors of human cancer cell lines

Synthesis, anticancer activity, and QSAR of 14 argentatin B analogs are described. Derivative 2-formyl-(16β,24R)-16,24-epoxy-25-hydroxycycloart-1-en-3-one was 35-50 times more potent than argentatin B to inhibit the growth of four human cancer cell lines. 3D-QSAR of K562 cell line growth inhibition was performed using the X-ray crystallographic structures of six derivatives as prototypes. Comparative molecular field analysis showed that a bulky group at C-2, a C1-C2 double bond, and a low electronic density near to C-25 increase the potency of these triterpenes. Experimental Log Ps for argentatin B and one derivative were 1-2 Log units more hydrophilic than the C Log P predicted values.