Abstract
The following complexes of type [PtCl(R)(ACRAMTU)](NO3)2 (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea)), derived from prototype 1 (with R = ethane-1,2-diamine), were synthesized: 2 (with R = (1R,2R)-1,2-diaminocyclohexane), 3 (with R = propane-1,3-diamine), 4 (with R = N1,N1,N2,N2-tetramethylethane-1,2-diamine), and 5 (with R = 2,2'-bipyridine). The DNA sequence specificity of the conjugates and their antiproliferative potential in HL-60 and H460 cells were investigated. Conjugate 3 showed the strongest non-cisplatin-type DNA damage in polymerase stop assays and superior cell kill efficacy in H460 lung cancer (IC50 = 70 nM).
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acridines / chemical synthesis*
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Acridines / pharmacology
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Base Sequence
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Cell Line, Tumor
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Cisplatin / pharmacology
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DNA Damage*
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Drug Screening Assays, Antitumor
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Humans
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Molecular Sequence Data
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Organoplatinum Compounds / chemical synthesis*
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Organoplatinum Compounds / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Thiourea / analogs & derivatives*
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Thiourea / chemical synthesis*
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Thiourea / pharmacology
Substances
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Acridines
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Antineoplastic Agents
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Organoplatinum Compounds
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chloro(1-(2-(acridin-9-ylamino)ethyl)-1,3-dimethylthiourea)(propane-1,3-diamine)platinum(II)
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Thiourea
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Cisplatin