Aromatic 2-chloroethyl urea derivatives and bioisosteres. Part 2: Cytocidal activity and effects on the nuclear translocation of thioredoxin-1, and the cell cycle progression

Recently, a subset of N-phenyl-N′-(2-chloroethyl)ureas (CEU) was found abrogating the nuclear translocation of thioredoxin-1 and arresting the cell cycle in G0/G1 phase. Several derivatives were prepared to assess their effect on cell cycle progression and on the intracellular location of Trx-1. Compounds 1–20, 21–40, and 41–60 exhibited GI50 between 1 and 80 μM. Immunocytochemistry analysis showed compounds 4, 6, 8, 10, 11, 23, 24, 26–31, 34, 37, 41, 44, 46–51, 53, 56, and 57 inhibiting the nuclear translocation of Trx-1. Our results suggest that increasing the electrophilic character of these molecules might enhance the antiproliferative activity at the expense of the selectivity toward thioredoxin-1 and the G0/G1 phase arrest.

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