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.
Hallur
Gurulingappa
G
Division of Chemical Therapeutics, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Jimeno
Antonio
A
Dalrymple
Susan
S
Zhu
Tao
T
Jung
M Katherine
MK
Hidalgo
Manuel
M
Isaacs
John T
JT
Sukumar
Saraswati
S
Hamel
Ernest
E
Khan
Saeed R
SR
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