title: New substituted 4H-chromenes as anticancer agents.
abstract: As a continuation of our efforts to discover and develop small molecules as anticancer agents, we identified GRI-394837 as an initial hit from similarity search on RGD and its analogs. Based on GRI-394837, we designed and synthesized a focused set of novel chromenes (4a-e) in a single step using microwave method. All five compounds showed activity in the nanomolar range (IC(50): 7.4-640 nM) in two melanoma, three prostate and four glioma cancer cell lines. The chromene 4e is active against all the cell lines and particularly against the A172 human glioma cell line (IC(50): 7.4 nM). Interestingly, in vitro tubulin polymerization assay shows 4e to be a weak tubulin polymerization inhibitor but it shows very strong cytotoxicity in cellular assays, therefore there must be additional unknown mechanism(s) for the anticancer activity. Additionally, the strong antiproliferative activity was verified by one of the selected chromene (4a) by the NCI 60 cell line screen. These results strongly suggest that the novel chromenes could be further developed as a potential therapeutic agent for a variety of aggressive cancers.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. spatil3@uthsc.edu
authors.forename: Shivaputra A
authors.initials: SA
authors.lastname: Patil
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaochen S
authors.initials: XS
authors.lastname: Li
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.forename: Terreia S
authors.initials: TS
authors.lastname: Jones
authors.forename: Amira
authors.initials: A
authors.lastname: Hosni-Ahmed
authors.forename: Renukadevi
authors.initials: R
authors.lastname: Patil
authors.forename: William L
authors.initials: WL
authors.lastname: Seibel
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Duane D
authors.initials: DD
authors.lastname: Miller
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001253:Astrocytes / Q000187:drug effects; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity
chemical_list: C575714:2-amino-4-(5-bromo-2-methoxyphenyl)-7-hydroxy-4H-chromene-3-carbonitrile; D000970:Antineoplastic Agents; D001578:Benzopyrans; D009842:Oligopeptides; D014404:Tubulin; D050257:Tubulin Modulators; C047981:arginyl-glycyl-aspartic acid