title: Synthesis and activity evaluation of tilorone analogs as potential anticancer agents.
abstract: Tilorone is an interferon inducer with anticancer activity. Twenty-two novel tilorone analogs were synthesized by improvements of fluorenone skeleton, side chains and amino groups to screen new anticancer agents. In vitro evaluation showed that ten new compounds had better anticancer activities than tilorone. Among them, 2c (IC50 < 7 μM against cancer cell lines and IC50 > 35 μM against non-cancer cell lines) and 5d (IC50 < 10 μM against cancer cell lines and IC50 > 53 μM against non-cancer cell lines) exhibited the best anticancer activities and selectivities. Pharmacophore modeling of highly active compounds was carried out by Molecular Operating Environment (MOE) to generate a visualized model for compound design in future study.
authors.affiliation: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China. zhoudingshan@whu.edu.cn
authors.forename: Dingshan
authors.initials: D
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Tuo
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Jianrong
authors.initials: J
authors.lastname: Xu
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Chen
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Rao
authors.forename: Yuling
authors.initials: Y
authors.lastname: Xiao
authors.forename: Xianming
authors.initials: X
authors.lastname: Hu
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013994:Tilorone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; D013994:Tilorone