RT Journal Article
SR Electronic
T1 Search for New Type of Anticancer Drugs with High Tumor Specificity and Less Keratinocyte Toxicity
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 5919
OP 5924
VO 37
IS 11
A1 YOSHIAKI SUGITA
A1 KOICHI TAKAO
A1 YOSHIHIRO UESAWA
A1 HIROSHI SAKAGAMI
YR 2017
UL http://ar.iiarjournals.org/content/37/11/5919.abstract
AB Most current anticancer drugs have shown excellent therapeutic effects on human oral squamous cell carcinoma (OSCC), but they also produce potent cytotoxicity in normal oral keratinocytes. This review article summarizes our extensive research of tumor specificity and keratinocyte toxicity of nine groups of compounds synthesized in our laboratory. Among a total of 133 compounds, (E)-3-[2-(4-hydroxyphenyl)ethenyl]-6-methoxy-4H-1-benzopyran-4-one [3] (classified as 3-styrylchromones), (E)-3-[2-(4-chlorophenyl)ethenyl]-7-methoxy-2H-1-benzopyran [4] (classified as 3-styryl-2H-chromenes) showed the highest tumor specificity with the least keratinocyte toxicity. Compound [3] induced apoptotic cell death in a human OSCC cell line, possibly by down-regulating the glycerophospholipid pathway. Quantitative structure–activity relationship analysis demonstrated that the tumor specificities of [3] and [4] were well correlated with chemical descriptors related to their molecular size and lipophilicity. Chemical modification of these lead compounds by introduction of appropriate functional groups is a crucial step towards manufacturing new types of anticancer drugs with reduced keratinocyte toxicity.