title: Anticancer activity of novel pyrido[2,3-b]indolizine derivatives: the relevance of phenolic substituents.
abstract: OBJECTIVE
  The potential of indolizine derivatives as anticancer agents has been shown through recent studies. Herein, we present our experimental results, showing that pyrido[2,3-b]indolizine derivatives are effective against colorectal cancer (CRC) cell lines.
  
  
  METHODS
  Several pyrido[2,3-b]indolizine derivatives were synthesized and their anticancer potential was evaluated against three CRC cell lines and two normal fibroblast cultures.
  
  
  RESULTS
  Our experiments identified 4-(3,4)-dihydroxyphenyl)-2-phenylpyrido[2,3-b]indolizine-10-carbonitrile (4f) as being active against all CRC cell lines at concentrations non-cytotoxic against fibroblast cultures. Additionally, cell-cycle analysis indicated that pyrido[2,3-b]indolizines can affect cell-cycle progression, with treated cells accumulating in the S- and G2/M-phase.
  
  
  CONCLUSIONS
  The hydroxyl groups in both the 3- and 4- positions of the aromatic substituent on C4 of the indolizine nucleus are crucial for activity against CRC cell lines. Further manipulation of the number and position of hydroxyl substituents on the aromatic rings may lead to improved anticancer activity of this class of compounds.
authors.affiliation: Albinusdreef 2, 2333ZA Leiden, The Netherlands. t.van_wezel@lumc.nl.
authors.forename: Arnoud
authors.initials: A
authors.lastname: Boot
authors.forename: Alexandra
authors.initials: A
authors.lastname: Brito
authors.forename: Tom
authors.initials: T
authors.lastname: VAN Wezel
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.forename: Marta
authors.initials: M
authors.lastname: Costa
authors.forename: Fernanda
authors.initials: F
authors.lastname: Proença
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D015179:Colorectal Neoplasms; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007212:Indolizines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D010636:Phenols / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007212:Indolizines; D010636:Phenols; C035094:indolizine
keywords: Colorectal cancer; HCT116; HT-29 and RKO cell lines; cell cycle; cytotoxicity; indolizine derivatives