Abstract
The design, synthesis and biological evaluation of lexitropsins bearing mixed heterocyclic and benzoheterocyclic moieties and tethered to an alpha-bromo acrylic moiety acting as alkylating moiety are reported, and structure-activity relationships determined. With respect to antiproliferative activity against L1210 and K562 cells, compounds 7 and 10 showed the greatest potency, while compounds 4 and 5 exhibit the lowest activity. Among the synthesized compounds 4-12, the derivative 10 was found to be the most potent member of this class and it is 70-fold more active than the bis-pyrrole counterpart 3 against L1210 cell line. In addition, the cytotoxicity of derivatives 5-12 against KB cells and the influence of different glutathione (GSH) concentrations on the cytotoxic effects was also investigated.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Alkylating / chemical synthesis*
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Antineoplastic Agents, Alkylating / chemistry
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Antineoplastic Agents, Alkylating / pharmacology
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Benzofurans / chemical synthesis
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Benzofurans / chemistry
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Drug Screening Assays, Antitumor
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Heterocyclic Compounds / chemical synthesis
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry
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Mice
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Molecular Structure
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Netropsin / analogs & derivatives*
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Netropsin / chemical synthesis
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Netropsin / chemistry
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Netropsin / pharmacology
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrroles / chemical synthesis
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Pyrroles / chemistry
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Structure-Activity Relationship
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Thiophenes / chemical synthesis
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Thiophenes / chemistry
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents, Alkylating
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Benzofurans
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Heterocyclic Compounds
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Imidazoles
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Pyrazoles
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Pyrroles
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Thiophenes
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benzothiophene
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lexitropsin
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Netropsin
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imidazole