title: Pyrrolo[2,3-b]quinoxalines as inhibitors of firefly luciferase: their Cu-mediated synthesis and evaluation as false positives in a reporter gene assay.
abstract: 2-Substituted pyrrolo[2,3-b]quinoxalines having free NH were prepared directly from 3-alkynyl-2-chloroquinoxalines in a single pot by using readily available and inexpensive methane sulfonamide (or p-toluene sulfonamide) as an ammonia surrogate. The reaction proceeded in the presence of Cu(OAc)(2) affording the desired product in moderate yield. The crystal structure analysis of a representative compound and its supramolecular interactions are presented. Some of the compounds synthesized exhibited inhibitory activities against luciferase that was supported by the predictive binding mode of these compounds with luciferase enzyme through molecular docking studies. The key observations disclosed here can alert users of luciferase reporter gene assays for possible false positive results due to the direct inhibition of luciferase.
authors.affiliation: Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, India.
authors.forename: Ali
authors.initials: A
authors.lastname: Nakhi
authors.forename: Md Shafiqur
authors.initials: MS
authors.lastname: Rahman
authors.forename: Ravada
authors.initials: R
authors.lastname: Kishore
authors.forename: Chandana Lakshmi T
authors.initials: CL
authors.lastname: Meda
authors.forename: Girdhar Singh
authors.initials: GS
authors.lastname: Deora
authors.forename: Kishore V L
authors.initials: KV
authors.lastname: Parsa
authors.forename: Manojit
authors.initials: M
authors.lastname: Pal
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D048888:Fireflies / Q000201:enzymology*; D017930:Genes, Reporter / Q000187:drug effects; D049409:Luciferases, Firefly / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D011758:Pyrroles; D011810:Quinoxalines; D049409:Luciferases, Firefly