2-Methyl-4-(phenyldiazenyl)phenyl picolinamide의 o-toluidinyl 구조가 AHR 길항저해 활성에 미치는 영향

국문 초록 (Abstract)

AHR(Aryl Hydrocarbon Receptor, 방향성탄화수소 수용체)은 리간드에 의해 활성화되어 체내 외래물질 의 대사를 조절하는 전사인자다. 생체 내에서 AHR의 생리학적 역할은 오랜 기간 연구되어 왔으나 antagonist를 비롯한 적절한 화학적 도구의 부재로 그 역할 규명이 제한되어 있다. AHR이 암을 비롯한 여러 질병의 발병기전에 관여되어 있다는 것이 밝혀짐에 따라 유효한 약물 표적으로 간주되나 화학적 도구의 부재로 인해 치료용 약물 개발 역시 제한되어 있다. 기존 antagonist 들은 저농도에서는 활성이 있으나 높은 농도에서는 AHR의 활성화를 유도하 는 부분적 antagonist이므로 순수 저해활성을 가지는 신규 antagonist의 개발이 필요하다. 본 연구에서는 2-methyl-4-(2-methylphenyldiazenyl)phenyl picolinamide의 o-toluidinyl 고리구조의 변경하여 활성을 평가하 는 유기화학과 분자생물학의 융합연구를 통하여 o-toluidinyl 구조를 최적화하였다.

다국어 초록 (Multilingual Abstract)

AHR is a transcription factor activated by aryl hydrocarbons, regulating the expression of XMEs (xenobiotics Metabolizing Enzymes). Even though the role of AHR in human physiology has been intensively investigated for the past decades, our understandings are still largely limited due to the deficiency of adequate chemical agents. In addition, it has been demonstrated that AHR correlates to pathogeneses for some diseases. Furthermore, emerging data suggest that the study on the AHR may provide a valid therapeutic target. Classical antagonists in current use are reported to be partial agonistic whereas a pure antagonist is demanded. In this study, o-toluidinyl ring structure of 2-methyl-4- (2-methylphenyldiazenyl)phenyl picolinamide has been modified into various structures to optimize the AHR antagonistic activity by means of convergence study of organic synthesis and molecular biology.

목차 (Table of Contents)

• 요약
• Abstract
• 1. 서론
• 1.1 AHR(방향성탄화수소 수용체)
• 1.2 AHR antagonist
• 1.3 연구 목표
• 2. 방법
• 2.1 유도체 합성
• 2.2 실험방법
• 3. 결과
• 3.1 유도체 합성
• 3.2 유도체들의 AHR 길항저해 활성 평가
• 4. 논의
• 4.1 AHR 리간드 구조
• 4.2 구조-활성 상관관계 연구
• 5. 결론 및 제언
• REFERENCES

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