트로포플라빈

Tropoflavin
트로포플라빈
7,8-dihydroxyflavone.svg
임상 데이터
기타 이름7,8-디히드록시플라본
약동학 데이터
바이오 어베이러빌리티~5% (마우스)[1]
반감기 제거30분 미만(마우스)[1]
식별자
  • 7,8-디히드록시-2-페닐-4H-크로멘-4-온
CAS 번호
PubChem CID
켐스파이더
유니
체비
CompTox 대시보드 (EPA )
ECHA 정보 카드100.048.903 Edit this at Wikidata
화학 및 물리 데이터
공식C15H10O4
몰 질량254.241 g/g−1/g
3D 모델(JSmol)
  • c1cc(cc1) c2cc(=O) c3cc(c(c3o2)O)o
  • InChI=1S/C15H10O4/c16-11-7-6-10-12(17)8-13(19-15(10)14(11)18)9-4-2-3-5-9/h1-8,16,18H
  • 키: COCYGNDCWFKTMF-UHFFFAOYSA-N

7,8-디히드록시플라본으로도 알려진 트로포플라빈은 갓마니아 에스쿨리폴리아, 트리닥스 프로쿰벤스, 프리뮬라 나무 [2][3][4]잎에서 발견되는 자연적으로 발생하는 플라본이다.뉴로트로핀 뇌유래 신경영양인자(BDNF)[5][6][7]의 주요 신호수용체인 트로포미오신 수용체 키나제 B(TrkB)(Kd ≤ 320nM)의 강력하고 선택적인 소분자 작용제로 작용하는 것으로 밝혀졌다.트로포플라빈은 경구적으로 생물적으로 이용 가능하며 혈액-뇌 [8][9]장벽을 통과할 수 있다.효능과 약물역동학이 크게 개선된 트로포플라빈의 프로드러그 R13(이전에는 R7)[10][11]은 알츠하이머병 치료를 위해 개발 중이다.

Tropoflavin 중추 신경계의 schizophrenia,[15]파킨슨 병 disease,[5]헌팅턴 disease,[16]인 근 위축성 측색 sclerosis,[17]외상성 뇌 injury,[18]뇌 ischemia,에 depression,[8]알츠하이머 disease,[12][13][14]인지력 결여 등과 같은 다양한 disorders,[7]의 동물 모델에 치료 효능을 보여 주었다.[19][20]취약 Xsyndrome,[21]과 레트 증후군.e.[22] 트로포플라빈은 또한 나이와 관련된 인지[23] 장애의 동물 모델에서 효과를 보여주며 건강한 [24][25]설치류에서 기억력 강화와 정서적 학습을 강화한다.또한 트로포플라빈은 TrkB [26]수용체에 대한 작용과는 무관하게 강력한 항산화 활성을 가지며, 글루탐산유도 흥분독성,[27][28] 6-히드록시도파민유도 도파민성 신경독성 및 산화스트레스유도 유전독성에 [29]대하여 보호한다.또한 필로폰 유도 도파민 신경독성을 차단하는 것으로 조사되었으며, 이는 이전과는 대조적으로 TrkB [30]의존성이 있는 것으로 확인되었다.

2017년 트로포플라빈과 보고된 다양한 소분자 TrkB 작용제가 실제로 TrkB의 직접 작용제가 아닐 수 있으며 다른 [31][32]방법으로 이들의 관찰된 효과를 매개할 수 있다는 증거가 발표되었다.

트로포플라빈은 체외([5]K = 10μM)[33]에서i 약한 방향족분해효소 억제제 역할을 하는 것으로 확인되었으나 체내에서는 그렇지 않을 수 있다는 증거가 있다.또한 알데히드 탈수소효소 및 에스트로겐 술포전달효소 in vitro(각각 K = 35μM, 1~3μM)를i 억제하는 것으로 확인되었으나, 이러한 활성은 아직 [5]생체 내에서 확인되지 않았다.다른 많은 플라보노이드와 달리 트로포플라빈은 17β-히드록시스테로이드 탈수소효소에 [34]억제 활성을 보이지 않는다.트로포플라빈은 또한 매우 높은 농도(Ki = 50 μM)[35][36]에서 시험관내 항에스트로겐 효과가 있는 것으로 관찰되었다.

디오스메틴(5,7,3'-트리히드록시-4'-메톡시플라본), 노르워고닌(5,7,8-트리히드록시플라본), 에우트로포플라빈(4'-디메틸아미노-7,8-디옥시플라빈)을 포함한 트로포플라빈의 다양한 근접구조유사체도 시험관내 TrkB작용제로서 작용하는 것으로 밝혀졌다.아히드록시플라본 및 3,7-디히드록시플라본.[37]반대로 고히드록실화 아날로그 고시페틴(3,5,7,8,3',4'-헥사히드록시플라본)은 [37]시험관내 TrkB의 길항제인 것으로 보인다.

트로포플라빈은 또한 어두운 단계에서 생쥐의 수면을 감소시키고 오렉신 A의 시상하부 수치를 감소시키는 것으로 확인되었지만 [38]생쥐의 오렉신 B는 감소시키지 않았다.

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레퍼런스

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