Antitumor activity of (-)-alpha-bisabolol-based thiosemicarbazones against human tumor cell lines.
A series of thiosemicarbazones deriving from the natural sesquiterpene (-)-alpha-bisabolol were synthesized and tested against a panel of eight human tumor cell lines to evaluate their anti-tumor potential. Some of the compounds exhibited inhibitory effects on the growth of a wide range of cancer cell lines, but myeloid leukemia cells (K-562) were especially sensitive to all tested thiosemicarbazones (GI(50) 0.01-4.22 microM). Among the analogues, the ketone derivative 3l was the most active, exhibiting potent antitumoral activity (GI(50) 0.01 microM) and high selectivity for K-562 cells (deltaTGI 505). It also demonstrated high cytotoxicity, with an LC(50) of 1.55 microM for the K-562 cells, but it showed only moderate selectivity (deltaLC(50) 38.5 microM). Through structure-activity relationship studies, we identified some structural requirement for the antitumoral activity exhibited by these promising compounds.
da Silva
Alan P
AP
Universidade Estadual de Maringá, Departamento de Química, Av. Colombo 5790, Maringá-PR 87020-900, Brazil.
Martini
Manuele V
MV
de Oliveira
Cecília M A
CM
Cunha
Silvio
S
de Carvalho
João E
JE
Ruiz
Ana L T G
AL
da Silva
Cleuza C
CC
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; D013882:Thiosemicarbazones; C004497:bisabolol