QSAR studies of PC-3 cell line inhibition activity of TSA and SAHA-like hydroxamic acids.
Quantitative structure-activity relationships (QSAR) for a series of new trichostatin A (TSA)-like hydroxamic acids for the inhibition of cell proliferation of the PC-3 cell line have been developed using molecular descriptors from Qikprop and electronic structure calculations. The best regression model shows that the PM3 atomic charge on the carbonyl carbon in the CONHOH moiety(Qco), globularity (Glob), and the hydrophilic component of the solvent-accessible surface area (FISA) describe the IC(50) of 19 inhibitors of the PC-3 cell line with activities ranging over five orders of magnitude with an R(2)=0.92 and F=59.2. This information will be helpful in the further design of novel anticancer drugs for treatment of prostate cancer and other diseases affected by HDAC inhibition.
Wang
Di-Fei
DF
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Wiest
Olaf
O
Helquist
Paul
P
Lan-Hargest
Hsuan-Yin
HY
Wiech
Norbert L
NL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D021281:Quantitative Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077337:Vorinostat; D006655:Histone Deacetylases