title: Ligand/PTC-free intramolecular Heck reaction: synthesis of pyrroloquinoxalines and their evaluation against PDE4/luciferase/oral cancer cell growth in vitro and zebrafish in vivo.
abstract: A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhibition of PDE4 without inhibiting luciferase. A ligand/PTC (phase transfer catalyst) free intramolecular Heck cyclization strategy was used to prepare these compounds, some of which showed significant inhibition of PDE4B (IC50≈ 5-14 μM) and growth inhibition of oral cancer cells (CAL 27) but not inhibition of luciferase in vitro. They also showed acceptable safety profiles but no apoptosis in zebrafish embryos.
authors.affiliation: Dr Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India. manojitpal@rediffmail.com.
authors.forename: P Vijaya
authors.initials: PV
authors.lastname: Babu
authors.forename: Soumita
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Girdhar Singh
authors.initials: GS
authors.lastname: Deora
authors.forename: Keerthana Sarma
authors.initials: KS
authors.lastname: Chennubhotla
authors.forename: Raghavender
authors.initials: R
authors.lastname: Medisetti
authors.forename: Swapna
authors.initials: S
authors.lastname: Yellanki
authors.forename: Pushkar
authors.initials: P
authors.lastname: Kulkarni
authors.forename: Shivashankar
authors.initials: S
authors.lastname: Sripelly
authors.forename: Kishore V L
authors.initials: KV
authors.lastname: Parsa
authors.forename: Kiranam
authors.initials: K
authors.lastname: Chatti
authors.forename: K
authors.initials: K
authors.lastname: Mukkanti
authors.forename: Manojit
authors.initials: M
authors.lastname: Pal
mesh_terms: D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D049109:Cell Proliferation / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D015394:Molecular Structure; D009062:Mouth Neoplasms / Q000188:drug therapy*; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology
chemical_list: D008024:Ligands; D058988:Phosphodiesterase 4 Inhibitors; D011810:Quinoxalines; D008156:Luciferases