Search for New Type of Anticancer Drugs with High Tumor Specificity and Less Keratinocyte Toxicity.

Abstract:

: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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Sugita Y,Takao K,Uesawa Y,Sakagami H

doi

10.21873/anticanres.12038

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

5919-5924

issue

11

eissn

0250-7005

issn

1791-7530

pii

37/11/5919

journal_volume

37

pub_type

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