Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Butyrates / chemical synthesis*
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Butyrates / chemistry
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Butyrates / pharmacology
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Cell Proliferation / drug effects
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HeLa Cells
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Humans
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Leukocytes, Mononuclear / drug effects
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Magnetic Resonance Spectroscopy
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Phenylbutyrates / chemical synthesis*
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Phenylbutyrates / chemistry
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Phenylbutyrates / pharmacology
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Structure-Activity Relationship
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Thioglycolates / chemical synthesis*
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Thioglycolates / chemistry
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Thioglycolates / pharmacology
Substances
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2-((carboxymethyl)sulfanyl)-4-oxo-4-(2,4,6-triethylphenyl)butanoic acid
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2-((carboxymethyl)sulfanyl)-4-oxo-4-(2,5-diisopropylphenyl)butanoic acid
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Antineoplastic Agents
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Butyrates
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Phenylbutyrates
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Thioglycolates