Abstract
Platinum-acridine conjugates were prepared from [PtCl2(ethane-1,2-diamine)] and the novel acridinylthioureas MeHNC(S)NMeAcr (6) and MeHNC(S)NMe(CH2CH2)NHAcr (15) by replacing one chloro leaving group in the cisplatin analogue with thiourea sulfur. In HL-60 leukemia cells, IC(50) values for 7 (Pt-tethered 6) and 16 (Pt-tethered 15) were 75 and 0.13 microM, respectively. In the ovarian cell lines 2008 and C13, 16 was active at micromolar concentrations and showed only partial cross-resistance with clinical cisplatin. Possible structure-activity relationships are discussed.
Publication types
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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 / chemistry
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Acridines / pharmacology
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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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Cisplatin / pharmacology
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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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Humans
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Magnetic Resonance Spectroscopy
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Organoplatinum Compounds / chemical synthesis*
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Organoplatinum Compounds / chemistry
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Organoplatinum Compounds / pharmacology
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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 / chemistry
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Thiourea / pharmacology
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Tumor Cells, Cultured
Substances
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Acridines
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Antineoplastic Agents
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Organoplatinum Compounds
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Thiourea
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Cisplatin