title: Search for inhibitors of bacterial and human protein kinases among derivatives of diazepines[1,4] annelated with maleimide and indole cycles.
abstract: Aminomethylation of 9b,10-dihydro-1H-indolo[1,7:4,5,6]pyrrolo[3,4:2,3][1,4]diazepino-[1,7-a]indole-1,3(2H)-diones or 1H-indolo[1,7:4,5,6]pyrrolo[3,4:2,3][1,4]diazepino[1,7-a]indole-1,3(2H)-diones resulted in dialkylaminomethyl derivatives. Alkylation of the nitrogen atom of maleimide moiety of polyannelated diazepines with 1,3-dibromopropane and subsequent reaction with thiourea or its N-alkyl derivatives gave isothiourea-carrying compounds. The compounds containing isothiourea moiety were active against individual human serine/threonine and tyrosine kinases at low micromolar concentrations. Dialkylaminomethyl derivatives of diazepines sensitized Streptomyces lividans with overexpressed aminoglycoside phosphotransferase type VIII (aphVIII) to kanamycin by inhibiting serine/threonine kinase(s) mediated aphVIII phosphorylation.
authors.affiliation: Vavilov Institute of General Genetics, 3 Gubkin Street, Moscow 119991, Russia.
authors.forename: Valery N
authors.initials: VN
authors.lastname: Danilenko
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Simonov
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Lakatosh
authors.forename: Michael H G
authors.initials: MH
authors.lastname: Kubbutat
authors.forename: Frank
authors.initials: F
authors.lastname: Totzke
authors.forename: Christoph
authors.initials: C
authors.lastname: Schächtele
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Elizarov
authors.forename: Olga B
authors.initials: OB
authors.lastname: Bekker
authors.forename: Svetlana S
authors.initials: SS
authors.lastname: Printsevskaya
authors.forename: Yuryi N
authors.initials: YN
authors.lastname: Luzikov
authors.forename: Marina I
authors.initials: MI
authors.lastname: Reznikova
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shtil
authors.forename: Maria N
authors.initials: MN
authors.lastname: Preobrazhenskaya
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008301:Maleimides / Q000737:chemistry*; D008956:Models, Chemical; D008968:Molecular Conformation; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D012694:Serine / Q000737:chemistry; D048170:Streptomyces lividans / Q000378:metabolism; D013890:Thiourea / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
chemical_list: D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; C043592:maleimide; D013912:Threonine; D012694:Serine; D011494:Protein Kinases; D013890:Thiourea