본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Angewandte Chemie v.130 no.29, 2018년, pp.9236 - 9240  

Monochalcoplatin: An Actively Transported, Quickly Reducible, and Highly Potent PtIV Anticancer Prodrug

Ma, Lili (Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave., Kowloon Tong, Hong Kong SAR, P. R. China ) ; Wang, Na (Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave., Kowloon Tong, Hong Kong SAR, P. R. China ) ; Ma, Rong (Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave., Kowloon Tong, Hong Kong SAR, P. R. China ) ; Li, Cai (Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave., Kowloon Tong, Hong Kong SAR, P. R. China ) ; Xu, Zoufeng (Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave., Kowloon Tong, Hong Kong SAR, P. R. China ) ; Tse, Man‐Kit (Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave., Kowloon Tong, Hong Kong SAR, P. R. China ) ; Zhu, Guangyu (Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave., Kow ) ;
  • 초록  

    Abstract Recently, Pt IV prodrugs have attracted much attention as the next generation of platinum‐based antineoplastic drug candidates. Here we report the discovery and evaluation of monochalcoplatin, a monocarboxylated Pt IV prodrug that is among the most cytotoxic Pt IV prodrugs to date. Compared with its dicarboxylated counterpart chalcoplatin, monochalcoplatin accumulates astonishingly effectively and rapidly in cancer cells, which is not ascribed to its lipophilicity. The prodrug is quickly reduced, causes DNA damage, and induces apoptosis, resulting in superior cytotoxicity with IC 50 values in the nanomolar range in both cisplatin‐sensitive and ‐resistant cells; these IC 50 values are up to 422‐fold higher than that of cisplatin. A detailed mechanistic study reveals that monochalcoplatin actively enters cells through a transporter‐mediated process. Moreover, monochalcoplatin shows significant antitumor activity in an in vivo colorectal tumor model. Our study implies a practical strategy for the design of more effective Pt IV prodrugs to conquer drug resistance by tuning both cellular uptake pathways and activation processes.


  • 주제어

    Aktiver Transport .   Antitumoraktivität .   Cisplatin .   Platin(IV)-Prodrugs.  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기