Modified carbazoles destabilize microtubules and kill glioblastoma multiform cells.

Authors

Philippe Diaz
Eric Horne
Cong Xu
Ernest Hamel
Michael Wagenbach
Ravil R Petrov
Benjamin Uhlenbruck
Brian Haas
Parvinder Hothi, Ivy Center for Advance Brain Tumor Treatment, Swedish Neuroscience Institute, 550 17th Ave, Seattle, WA, 98122, USA.Follow
Linda Wordeman
Rick Gussio
Nephi Stella

Document Type

Article

Publication Date

11-5-2018

Keywords

Antineoplastic Agents; Carbazoles; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Glioblastoma; Humans; Microtubules; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship; Carbazole; Colchicine; Gliomas; Microtubules

Abstract

Small molecules that target microtubules (MTs) represent promising therapeutics to treat certain types of cancer, including glioblastoma multiform (GBM). We synthesized modified carbazoles and evaluated their antitumor activity in GBM cells in culture. Modified carbazoles with an ethyl moiety linked to the nitrogen of the carbazole and a carbonyl moiety linked to distinct biaromatic rings exhibited remarkably different killing activities in human GBM cell lines and patient-derived GBM cells, with IC

Area of Special Interest

Cancer

Area of Special Interest

Neurosciences (Brain & Spine)

Specialty/Research Institute

Oncology

Specialty/Research Institute

Neurosciences