title: A dihydroindolizino indole derivative selectively stabilizes G-quadruplex DNA and down-regulates c-MYC expression in human cancer cells.
abstract: BACKGROUND
  Telomeric and NHE III1, a c-MYC promoter region is abundant in guanine content and readily form G-quadruplex structures. Small molecules that stabilize G-quadruplex DNA were shown to reduce oncoprotein expression, initiate apoptosis and they may function as anticancer molecules.
  
  
  METHODS
  Electrospray ionization mass spectrometry, spectroscopy, isothermal titration calorimetry, Taq DNA polymerase stop assay, real time PCR and luciferase reporter assay. Cell migration assay to find out the effect of derivatives on normal as well as cancer cell proliferation.
  
  
  RESULTS
  Among three different dihydroindolizino indole derivatives, 4-cyanophenyl group attached derivative has shown maximum affinity, selective interaction and higher stability towards G-quadruplex DNA over dsDNA. Further, as a potential G-quadruplex DNA stabilizer, 4-cyanophenyl linked dihydroindolizino indole derivative was found to be more efficient in inhibiting in vitro DNA synthesis, c-MYC expression and cancer cell proliferation among human cancer cells.
  
  
  CONCLUSIONS
  The present study reveals that dihydroindolizino indole derivative having 4-cyanophenyl group has potential to stabilize G-quadruplex DNA and exhibit anticancer activity.
  
  
  CONCLUSIONS
  These studies are useful in the identification and synthesis of lead derivatives that will selectively stabilize G-quadruplex DNA and function as anticancer agents.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India. Electronic address: nagesh@ccmb.res.in.
authors.forename: Narayana
authors.initials: N
authors.lastname: Nagesh
authors.affiliation: National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: G
authors.initials: G
authors.lastname: Raju
authors.affiliation: National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: R
authors.initials: R
authors.lastname: Srinivas
authors.affiliation: Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: P
authors.initials: P
authors.lastname: Ramesh
authors.affiliation: Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: M Damoder
authors.initials: MD
authors.lastname: Reddy
authors.affiliation: Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Ch Raji
authors.initials: ChR
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D002151:Calorimetry; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D015536:Down-Regulation / Q000187:drug effects*; D054856:G-Quadruplexes; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008956:Models, Chemical; D015394:Molecular Structure; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry; D044366:Transition Temperature / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA
keywords: Anticancer activity; Dihydroindolizino indole; ESI-MS; Reduce c-MYC expression; Selective stabilization of G-quadruplex DNA; Spectroscopy