Abstract
Analogs of hemiasterlin (1) and HTI-286 (2), which contain various aromatic rings in the A segment, were synthesized as potential inhibitors of tubulin polymerization. The structure-activity relationships related to stereo- and regio-chemical effects of substituents on the aromatic ring in the A segment were studied. Analogs, which carry a meta-substituted phenyl ring in the A segment show comparable activity for inhibition of tubulin polymerization to 2, as well as in the cell proliferation assay using KB cells containing P-glycoprotein, compared to those of 1 and 2.
MeSH terms
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Animals
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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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Biopolymers
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Cell Proliferation / drug effects
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Humans
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KB Cells
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Melanoma, Experimental / drug therapy
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Mice
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Mice, Nude
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Tubulin / chemistry*
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Tubulin Modulators*
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Biopolymers
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HTI-286
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Oligopeptides
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Tubulin
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Tubulin Modulators
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hemiasterlin