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.
Arantes
Francisco F P
FF
Department of Chemistry, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, CEP 36570-000, Viçosa, MG, Brazil.
Barbosa
Luiz C A
LC
Maltha
Célia R A
CR
Demuner
Antônio J
AJ
Marçal da Costa
Patricia
P
Ferreira
José R O
JR
Costa-Lotufo
Letícia V
LV
Moraes
Manoel O
MO
Pessoa
Cláudia
C
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