2-[(Carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids selectively suppressed proliferation of neoplastic human HeLa cells. A SAR/QSAR study.
A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 microM/L. Two compounds exhibit antiproliferative activity in sub-micromolar concentrations. Five compounds act in low micromolar concentrations (<2 microM/L). The most active compounds exert lower cytotoxicity toward healthy human peripheral blood mononuclear cells (PBMC and PBMC+PHA) (selectivity indexes > 10). A strong structure-activity relationship, using estimated log P values and BCUT descriptors, was observed.
Drakulić
Branko J
BJ
Institute for Chemistry, Technology and Metallurgy, Njegoseva 12, Belgrade, Serbia and Montenegro. bdrakuli@helix.chem.bg.ac.yu
Juranić
Zorica D
ZD
Stanojković
Tatjana P
TP
Juranić
Ivan O
IO
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002087:Butyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D010654:Phenylbutyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013864:Thioglycolates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C504525:2-((carboxymethyl)sulfanyl)-4-oxo-4-(2,4,6-triethylphenyl)butanoic acid; C504524:2-((carboxymethyl)sulfanyl)-4-oxo-4-(2,5-diisopropylphenyl)butanoic acid; D000970:Antineoplastic Agents; D002087:Butyrates; D010654:Phenylbutyrates; D013864:Thioglycolates