Synthesis and Biological Activity of Novel Retinamide and Retinoate Derivatives
-
- Um Soo-Jong
- Department of Bioscience and Biotechnology / Institute of Bioscience, Sejong University
-
- Kwon Youn-Ja
- Chebigen Inc., 305-B, Chungmugwan, Sejong University
-
- Han Hye-Sook
- Chebigen Inc., 305-B, Chungmugwan, Sejong University
-
- Park Si-Ho
- Chebigen Inc., 305-B, Chungmugwan, Sejong University
-
- Park Myoung-Soon
- Chebigen Inc., 305-B, Chungmugwan, Sejong University
-
- Rho Young-Soy
- Department of Chemistry, Chonbuk National University, Korea
-
- Sin Hong-Sig
- Chebigen Inc., 305-B, Chungmugwan, Sejong University
この論文をさがす
抄録
Retinoic acid and its amide derivative, N-(4-hydroxyphenyl)retinamide (4-HPR), have been proposed as chemopreventative and chemotherapeutic agents. However, their low cytotoxic activity and water solubility limit their clinical use. In this study, we synthesized novel retinoid derivatives with improved cytotoxicity against cancer cells and increased hygroscopicity. Our syntheses were preceded by selective O-acylation and N-acylation, which led to the production of retinoate and retinamide derivatives, respectively, in one pot directly from aminophenol derivatives and retinoic acid without protection. Transcription assays in COS-1 cells indicated that the N-acylated derivatives (2A—5A) and 4-HPR (1A) were much weaker ligands for all three subtypes of retinoic acid receptor (RAR) than all-trans retinoic acid (ATRA), although they showed some selectivity for RARβ and RARγ. In contrast, the O-acylated retinoate derivatives (1B—5B) activated all three RAR isotypes without specificity to an extent similar to ATRA. The cytotoxicity was determined using an MTT assay with HCT116 colon cancer cells, and the IC50 of N-acylated retinamide derivative 4A and O-acylated retinoate derivative 5B was 1.67 μM and 0.65 μM, respectively, which are about five and 13-fold better than that of 4-HPR (8.21 μM), a prototype N-acylated derivative. When retinoate derivative 5B was coupled to organic acid salts, the resulting salt derivatives 5C and 5D had RAR activation and cytotoxicity similar to those of 5B. These data may delineate the relationship between the structure and function of retinoate and retinamide derivatives.
収録刊行物
-
- CHEMICAL & PHARMACEUTICAL BULLETIN
-
CHEMICAL & PHARMACEUTICAL BULLETIN 52 (5), 501-506, 2004
公益社団法人 日本薬学会
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1390282679148081152
-
- NII論文ID
- 110003615603
-
- NII書誌ID
- AA00602100
-
- ISSN
- 13475223
- 00092363
-
- NDL書誌ID
- 6931095
-
- PubMed
- 15133197
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可