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 G(0)/G(1) 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 GI(50) between 1 and 80 microM. 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 G(0)/G(1) phase arrest.
Fortin
Jessica S
JS
Unité des Biotechnologies et de Bioingénierie, CHUQ, Hôpital Saint-François d'Assise, Québec, Que., Canada G1L 3L5. jessica.fortin.1@ulaval.ca
Côté
Marie-France
MF
Lacroix
Jacques
J
Petitclerc
Eric
E
C-Gaudreault
René
R
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013879:Thioredoxins / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013879:Thioredoxins; D014508:Urea