Journal of the Korea Convergence Society (한국융합학회논문지)

Korea Convergence Society (한국융합학회)
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Study on the Effects of Phenyldiazenylanilines on the Activation of Arylhydrocarbon Receptor

Phenyldiazenylaniline 유도체가 방향족탄화수소 수용체의 활성에 미치는 영향

  • Lee, Hyosung (School of Food and Pharmaceutical Science & Engineering, Seowon University)
  • 이효성 (서원대학교 제약식품공학부)
  • Received : 2018.11.15
  • Accepted : 2019.01.20
  • Published : 2019.01.28
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Abstract

AHR regulates the expression of xenobiotics metabolizing enzymes (XMEs) as a transcription fact upon binding of ligands that are mainly aryl hydrocarbons. The role of AHR in human physiology has been intensively investigated for the past decades, however our understanding on AHR yet to be elucidated largely due to the lack of proper chemical agents. It has been demonstrated that AHR correlates to pathogenesis for some diseases in recent studies suggesting that the study on the AHR may provide a valid therapeutic target. Classical antagonists in current use are reported to be partially agonistic whereas a pure antagonist is yet to be found. In this study, phenyldiazenylaniline has been designed based on the structure of two known AHR antagonist, Resveratrol and CH223191. The derivatives of phenyldiazenylaniline have been prepared and subjected to assessment as an AHR antagonist in order to optimize the AHR antagonistic activity of the designed structure by means of convergence study of organic synthesis and molecular biology.

방향성 탄화수소 수용체(Aryl Hydrocarbon Receptor, AHR)은 리간드에 의해 활성화되어 체내 외래물질의 대사를 조절하는 전사인자다. 생체 내에서 AHR의 생리학적 역할은 오랜 기간 연구되어 왔으나 길항제를 비롯한 적절한 화학적 도구의 부재로 그 역할 규명이 제한되어 있다. AHR이 다양한 질병의 발병기전에 관여되어 있다는 것이 밝혀짐에 따라 유효한 약물 표적으로 인식되고 있으나 치료나 예방을 위한 유효한 약물은 아직 개발되지 않았다. 길항제로 알려진 화합물들은 낮은 농도에서는 길항활성이 있어 연구 목적으로는 활용되고 있으나 높은 농도에서는 AHR을 활성화하는 부분적 agonist로 작용한다. 이에 AHR 활성화를 유도하지 않는 순수한 길항제의 개발이 필요하다. 본 연구에서는 이미 알려진 AHR 길항제인 Resveratrol과 CH223191의 구조를 기반으로 phenyldiazenylanline 구조를 설계하였고 이를 골격으로 다양한 유도체를 합성하고 화학적 구조와 생물학적 활성의 상관 관계에 대한 융합 연구를 통하여 신규 AHR 길항제를 도출하였다.

Keywords

OHHGBW_2019_v10n1_285_f0001.png 이미지

Fig. 1. Design of phneyldiazenylanilines as an AHR antagonist.

OHHGBW_2019_v10n1_285_f0002.png 이미지

Fig. 2. Synthesis of phenyldiazenylanilines

Table. 1. Antagonistic activities of phenyldiazenylanilines.

OHHGBW_2019_v10n1_285_t0001.png 이미지

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