Synthesis of novel α-santonin derivatives as potential cytotoxic agents.
Ten novel α-santonin derivatives have been synthesized as cytotoxic agents. The in vitro antitumor activity of these compounds has been evaluated against cancer cells lines. Structure-activity relationships indicate that α-methylene-γ-lactone and endoperoxide functionalities play important roles in conferring cytotoxicity. The compounds 2-4, possessing the α-methylene-γ-lactone group showed IC50 values between 5.70 and 16.40 μM. Mixture of isomers 5 and 6, with the α-methylene-γ-lactone and endoperoxide functionalities, displayed the greatest activity, with IC50 values between 1.45 and 4.35 μM. The biological assays conducted with normal cells revealed that the compounds 2, 5 and 6 are selective against cancer cells lines tested. Bioactive lactones described herein and in our previous report did not cause disruption of the cell membrane in mouse erythrocytes.
Department of Chemistry, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, CEP 36570-000, Viçosa, MG, Brazil.
Francisco F P
FF
Arantes
Luiz C A
LC
Barbosa
Célia R A
CR
Maltha
Antônio J
AJ
Demuner
Patricia
P
Marçal da Costa
José R O
JR
Ferreira
Letícia V
LV
Costa-Lotufo
Manoel O
MO
Moraes
Cláudia
C
Pessoa
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D012500:Santonin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D012500:Santonin