title: Synthesis of 5α,8α-Ergosterol Peroxide 3-Carbamate Derivatives and a Fluorescent Mitochondria-Targeting Conjugate for Enhanced Anticancer Activities.
abstract: Inspired by the significant anticancer activity of our previously screened natural ergosterol peroxide (1), we synthesized and characterized a series of novel ergosterol peroxide 3-carbamate derivatives. The antiproliferative activities of the synthesized compounds against human hepatocellular carcinoma cells (HepG2, SK-Hep1) and human breast cancer cells (MCF-7, MDA-MB231) were investigated. 5α,8α-Epidioxyergosta-3-yl-(piperazine-1)carbamate (3 d) and 5α,8α-epidioxyergosta-3-yl-(piperidin-4-methylamine)carbamate (3 f) and their hydrochloride salts exhibited significant in vitro antiproliferative activities against the tested tumor cell lines, with IC50values ranging from 0.85 to 4.62 μm. Furthermore, fluorescent imaging showed that the designed coumarin-3 d conjugate (5) localized mainly in mitochondria, leading to enhanced anticancer activities over the parent structure 1. As a whole, it appeared that substituent changes at the C3 position could serve as a promising launch point for further design of this type of steroidal anticancer agent.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Bu
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Cao
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, ON, M4N 3M5, Canada.
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Chengchu
authors.initials: C
authors.lastname: Zeng
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.|Beijing Key Laboratory of Environmental and Viral Oncology, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry; D018360:Crystallography, X-Ray; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D003374:Coumarins; D005456:Fluorescent Dyes; C030123:coumarin; C036071:ergosterol-5,8-peroxide; D004875:Ergosterol
keywords: carbamates; coumarins; ergosterol peroxide; fluorescence imaging; mitochondria