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- W1990928371 endingPage "6857" @default.
- W1990928371 startingPage "6845" @default.
- W1990928371 abstract "Two systematic series of increasingly hydrophilic derivatives of duocarmycin SA that feature the incorporation of ethylene glycol units (n = 1–5) into the methoxy substituents of the trimethoxyindole subunit are described. These derivatives exhibit progressively increasing water solubility along with progressive decreases in cell growth inhibitory activity and DNA alkylation efficiency with the incremental ethylene glycol unit incorporations. Linear relationships of cLogP with −log IC50 for cell growth inhibition and −log AE (AE = cell-free DNA alkylation efficiency) were observed, with the cLogP values spanning the productive range of 2.5–0.49 and the −log IC50 values spanning the range of 11.2–6.4, representing IC50 values that vary by a factor of 105 (0.008 to 370 nM). The results quantify the fundamental role played by the hydrophobic character of the compound in the expression of the biological activity of members in this class (driving the intrinsically reversible DNA alkylation reaction) and define the stunning magnitude of its effect." @default.
- W1990928371 created "2016-06-24" @default.
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- W1990928371 creator A5069045048 @default.
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- W1990928371 date "2013-08-29" @default.
- W1990928371 modified "2023-10-09" @default.
- W1990928371 title "A Fundamental Relationship between Hydrophobic Properties and Biological Activity for the Duocarmycin Class of DNA-Alkylating Antitumor Drugs: Hydrophobic-Binding-Driven Bonding" @default.
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