Synthesis, cytotoxicity, and DNA-topoisomerase inhibitory activity of new asymmetric ureas and thioureas.
A new series of N-3,3-diphenylpropyl-N-(p-X-benzyl)-N'-phenylureas (5a-g) and thioureas (6a-g) were synthesized by the reaction of secondary amines and phenyl isocyanate or isothiocyanate. The cytotoxic effects of the urea and thiourea derivatives were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against Ehrlich carcinoma and K562 human leukemia cells. Moreover, the activity of compounds in the inhibition of DNA topoisomerases I and II-alpha was tested. The results indicated that the compounds presented important and promising antiproliferative action.
Esteves-Souza
Andressa
A
Universidade Federal Rural do Rio de Janeiro, Seropédica, 23851-970, RJ, Brazil.
Pissinate
Kenia
K
Nascimento
Maria da Graça
Mda G
Grynberg
Noema Faiga
NF
Echevarria
Aurea
A
D000818:Animals; D000951:Antigens, Neoplasm; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013055:Spectrophotometry, Infrared; D013890:Thiourea / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014508:Urea / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014508:Urea; D004250:DNA Topoisomerases, Type II; D013890:Thiourea