Abstract
Novel ABI-III compounds were designed and synthesized based on our previously reported ABI-I and ABI-II analogues. ABI-III compounds are highly potent against a panel of melanoma and prostate cancer cell lines, with the best compound having an average IC(50) value of 3.8 nM. They are not substrate of Pgp and thus may effectively overcome Pgp-mediated multidrug resistance. ABI-III analogues maintain their mechanisms of action by inhibition of tubulin polymerization.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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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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Cell Line, Tumor
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Drug Resistance, Neoplasm
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Drug Screening Assays, Antitumor
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Male
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Melanoma
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Models, Molecular
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Paclitaxel / pharmacology
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Prostatic Neoplasms
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Structure-Activity Relationship
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Tubulin Modulators / chemical synthesis*
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Tubulin Modulators / chemistry
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Tubulin Modulators / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antineoplastic Agents
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Imidazoles
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Tubulin Modulators
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Paclitaxel