title: Optimized N-phenyl-N'-(2-chloroethyl)ureas as potential antineoplastic agents: synthesis and growth inhibition activity.
abstract: In our ongoing research program aimed at the optimization of microtubule-self-assembly disrupting agents, we have prepared three series of phenylurea analogues (CEU), derived from N-(3-omega-hydroxyalkyl or 4-omega-hydroxyalkyl or 3-omega-hydroxyalkynyl)-phenyl-N'-(2-chloroethyl)ureas. Most compounds exhibit potent growth inhibitory activity on human colon carcinoma HT-29, human skin melanoma M21, and human breast carcinoma MCF-7 tumor cell lines, with a GI50 ranging from 250 nM to 8 microM. Among these new molecules, three CEUs exhibit GI50 in the nanomolar range. They are more potent by approximately an order of magnitude than previously described CEU analogues. As such, they are attractive hit compounds for the development of potent new alkylating antitubulin drugs.
authors.affiliation: Unité de biotechnologie et de bioingénierie, C.H.U.Q., Hôpital Saint-François d'Assise, Université Laval, Québec, QC, Canada G1L 3L5. moreaumanu@yahoo.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Moreau
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fortin
authors.forename: Michel
authors.initials: M
authors.lastname: Desjardins
authors.forename: Jean L C
authors.initials: JL
authors.lastname: Rousseau
authors.forename: Eric
authors.initials: E
authors.lastname: Petitclerc
authors.forename: René
authors.initials: R
authors.lastname: C-Gaudreault
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; D010671:Phenylurea Compounds