title: Quinazoline derivative from indigenous isolate, Nocardiopsis alba inhibits human telomerase enzyme.
abstract: OBJECTIVE
  Aim of this study was isolation and screening of various secondary metabolites produced by indigenous isolates of soil Actinomycetes for human telomerase inhibitory activity.
  
  
  RESULTS
  Extracellular extract from culture suspension of various soil Actinomycetes species were tested for telomerase inhibitory activity. The organism which produced telomerase inhibitor was identified by 16S rRNA gene sequencing. The active fraction was purified by HPLC and analysed by GC-MS to identify the compound. In GC-MS analysis, the active principle was identified as 3-[4'-(2″-chlorophenyl)-2'-thiazolyl]-2,4-dioxo-1,2,3,4-tetrahydro quinazoline. The G-quadruplex stabilizing ability of the compound was checked by molecular docking and simulation experiments with G-quadruplex model (PDB ID-1L1H). The selective binding ability of the compound with G-quadruplex over Dickerson-Drew dodecamer DNA structures showed that the compound possess high selectivity towards G-quadruplex.
  
  
  CONCLUSIONS
  Quinazoline derivative isolated from an indigenous strain of Nocardiopsis alba inhibited telomerase. Molecular docking and simulation studies predicted that this compound is a strong stabilizer of G-quadruplex conformation. It also showed a preferable binding to G-quadruplex DNA over normal DNA duplex.
  
  
  CONCLUSIONS
  This particular compound can be suggested as a suitable compound for developing a future anticancer drug. The selectivity towards G-quadruplex over normal DNA duplex gives a clue that it is likely to show lower cytotoxicity in normal cells.
authors: Department of Microbial Biotechnology, Bharathiar University, Coimbatore, India.
authors: K G
authors: KG
authors: Kiran
authors: Department of Microbial Biotechnology, Bharathiar University, Coimbatore, India.
authors: M
authors: M
authors: Thandeeswaran
authors: Department of Microbial Biotechnology, Bharathiar University, Coimbatore, India.
authors: K A
authors: KA
authors: Ayub Nawaz
authors: Department of Bioinformatics, Bharathiar University, Coimbatore, India.
authors: M
authors: M
authors: Easwaran
authors: Department of Microbial Biotechnology, Bharathiar University, Coimbatore, India.
authors: K K
authors: KK
authors: Jayagopi
authors: Department of Microbial Biotechnology, Bharathiar University, Coimbatore, India.
authors: L
authors: L
authors: Ebrahimi
authors: School of Life Science, Karpagam University, Coimbatore, India.
authors: M
authors: M
authors: Palaniswamy
authors: Department of Microbial Biotechnology, Bharathiar University, Coimbatore, India.
authors: R
authors: R
authors: Mahendran
authors: Department of Microbial Biotechnology, Bharathiar University, Coimbatore, India.
authors: J
authors: J
authors: Angayarkanni
mesh_terms: D039903:Actinobacteria / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D011799:Quinazolines / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: C000615819:3-(4'-(2'-chlorophenyl)-2'-thiazolyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008024:Ligands; D011799:Quinazolines; D004247:DNA; C509186:TERT protein, human; D019098:Telomerase
keywords: Actinomycetes; bioinformatics; biopharmaceuticals; bioproducts; molecular docking; polymerase chain reaction; quinazoline; telomerase inhibitors