Synthesis and differential antiproliferative activity of Biginelli compounds against cancer cell lines: Monastrol, oxo-monastrol and oxygenated analogues.
The synthesis and differential antiproliferative activity of monastrol (1a), oxo-monastrol (1b) and eight oxygenated derivatives 3a,b-6a,b on seven human cancer cell lines are described. For all evaluated cell lines, monastrol (1a) was shown to be more active than its oxo-analogue, except for HT-29 cell line, suggesting the importance of the sulfur atom for the antiproliferative activity. Monastrol (1a) and the thio-derivatives 3a, 4a and 6a displayed relevant antiproliferative properties with 3,4-methylenedioxy derivative 6a being approximately more than 30 times more potent than monastrol (1a) against colon cancer (HT-29) cell line.
Russowsky
Dennis
D
Instituto de Química, Universidade Federal do Rio Grande do Sul, CP 15003, 91501-970 Porto Alegre, RS, Brazil. dennis@iq.ufrgs.br
Canto
Rômulo F S
RF
Sanches
Sergio A A
SA
D'Oca
Marcelo G M
MG
de Fátima
Angelo
A
Pilli
Ronaldo A
RA
Kohn
Luciana K
LK
Antônio
Márcia A
MA
de Carvalho
João Ernesto
JE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010100:Oxygen / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013871:Thiones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011743:Pyrimidines; D013871:Thiones; C400223:monastrol; D010100:Oxygen