Benzoylphenylurea sulfur analogues with potent antitumor activity.
A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to 1 (NSC-639829), against cancer cell lines. 6n was more effective than 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC(50) of 2.1 microM.
Division of Chemical Therapeutics, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Gurulingappa
G
Hallur
Antonio
A
Jimeno
Susan
S
Dalrymple
Tao
T
Zhu
M Katherine
MK
Jung
Manuel
M
Hidalgo
John T
JT
Isaacs
Saraswati
S
Sukumar
Ernest
E
Hamel
Saeed R
SR
Khan
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C509931:1-(2-aminobenzoyl)-3-(4-(5-bromopyrimidin-2-ylsulfanyl)phenyl)urea; C509932:1-(4-(5-bromopyrimidin-2-ylsulfanyl)phenyl)-3-(2-nitrobenzoyl)urea; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011743:Pyrimidines; D050257:Tubulin Modulators