title: Evaluation of 5-aminoisoquinoline (5-AIQ), a novel PARP-1 inhibitor for genotoxicity potential in vitro and in vivo.
abstract: 5-aminoisoquinoline (5-AIQ) is an active PARP-1 inhibitor as well as an important functional group various drugs. Quinolines are generally known as mutagenic and carcinogenic in various in vitro and in vivo systems, while both positive and negative findings are available on the mutagenic potential of several isoquinolines. Since no literature is available on the genotoxicity of 5-AIQ, a battery of tests were conducted, in accordance with relevant OECD protocols, such as bacterial reverse mutation test, in vitro chromosomal aberration test, and bone marrow micronucleus test in mouse. These studies demonstrate that 5-AIQ does not possess genotoxic activity both with in vitro and in vivo systems. The findings substantiate the therapeutic value of 5-AIQ.
authors.affiliation: Division of Toxicology, Biological Research, Glenmark Pharmaceuticals Ltd., Glenmark Research Centre, A-607, TTC Industrial Area, MIDC, Mahape, Navi Mumbai-400709, India. vinodkr@glenmarkpharma.com
authors.forename: K R
authors.initials: KR
authors.lastname: Vinod
authors.forename: Saurabh
authors.initials: S
authors.lastname: Chandra
authors.forename: Sharad K
authors.initials: SK
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D009152:Mutagenicity Tests; D009154:Mutation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018570:Risk Assessment; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: C549098:5-aminoisoquinoline; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors