title: Regioselective acylation of congeners of 3-amino-1H-pyrazolo[3,4-b]quinolines, their activity on bacterial serine/threonine protein kinases and in vitro antibacterial (including antimycobacterial) activity.
abstract: It was found by virtual screening that 3-amino-1H-pyrazolo[3,4-b]quinolines could have wide protein kinase inhibitory activity. Amides of titled amines and thioureas were synthesized regioselectively. 3-Amino-7-methoxy-1H-pyrazolo[3,4-b]quinoline demonstrated in vitro significant inhibitory activity on bacterial serine/threonine protein kinases (inhibition of resistance to kanamycin in Streptomyces lividans regulated by protein kinases). The studies of Structure Activity Relationship (SAR) showed that the substitution of the NH2 group and 1-NH of pyrazole ring or aromatic ring at the position 6 decreased or removed inhibitory activity.
authors.affiliation: Gause Institute of New Antibiotics , B. Pirogovskaya 11, Moscow, 119313 , Russia.
authors.forename: Gennady B
authors.initials: GB
authors.lastname: Lapa
authors.forename: O B
authors.initials: OB
authors.lastname: Bekker
authors.forename: E P
authors.initials: EP
authors.lastname: Mirchink
authors.forename: V N
authors.initials: VN
authors.lastname: Danilenko
authors.forename: M N
authors.initials: MN
authors.lastname: Preobrazhenskaya
mesh_terms: D000215:Acylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D020102:Mycobacterium smegmatis / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D048170:Streptomyces lividans / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011804:Quinolines; D017346:Protein Serine-Threonine Kinases