Abstract
Novel thiourea- and guanidine-modified acridine-4-carboxamides (4, 7) and a corresponding platinum-intercalator conjugate (4') have been synthesized and evaluated as cytotoxic agents in human promyelocytic leukemia, HL-60, and a non-small cell lung cancer, NCI-H460. Modification of thiourea sulfur in derivative 4 with a DNA platinating moiety, giving 4', resulted in a pronounced cytotoxic enhancement, and the conjugate proved to be the most active of the newly synthesized compounds in NCI-H460 cells. Conjugate 4' represents a new chemotype with potential applications in the treatment of chemoresistant tumors.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acridines / chemistry
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Acridines / pharmacology*
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Chemistry, Pharmaceutical / methods
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Drug Design
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Drug Resistance, Neoplasm
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Drug Screening Assays, Antitumor
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Guanidine / analogs & derivatives*
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Guanidine / chemistry
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HL-60 Cells
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Humans
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Inhibitory Concentration 50
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Models, Chemical
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Platinum / chemistry*
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Structure-Activity Relationship
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Thiourea / chemistry*
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Urea / analogs & derivatives*
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Urea / chemistry
Substances
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Acridines
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Antineoplastic Agents
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guanidine carboxamide
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Platinum
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Urea
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Thiourea
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Guanidine