title: Synthesis and in vitro antimycobacterial and isocitrate lyase inhibition properties of novel 2-methoxy-2'-hydroxybenzanilides, their thioxo analogues and benzoxazoles.
abstract: A new series of 2-methoxy-2'-hydroxybenzanilide derivatives and their thioxo analogues have been synthesised and characterised by IR, NMR and elemental analysis. These compounds were investigated for their in vitro antimycobacterial activities against Mycobacterium tuberculosis 331/88, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80, clinically isolated M. kansasii 6509/96 and the ability to act as in vitro isocitrate lyase inhibitors. The best ICL inhibitors were two compounds from the thiobenzanilide group (8f, 8m), which exhibited an inhibition potential that was equal to the standard compound, 3-nitropropionic acid. In addition, the best antimycobacterial properties were exhibited by benzanilide derivatives 6h, 6k and 6l with 5-Cl and 4' or 5' Cl/Br substitution. For all the thiobenzanilide derivatives tested, two conformers were observed in the NMR spectra, which is most likely due to the hindered rotation of the C-N bond.
authors.affiliation: Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Inorganic and Organic Chemistry, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Ján
authors.initials: J
authors.lastname: Kozic
authors.forename: Eva
authors.initials: E
authors.lastname: Novotná
authors.forename: Marie
authors.initials: M
authors.lastname: Volková
authors.forename: Jiřina
authors.initials: J
authors.lastname: Stolaříková
authors.forename: František
authors.initials: F
authors.lastname: Trejtnar
authors.forename: Vladimír
authors.initials: V
authors.lastname: Wsól
authors.forename: Jarmila
authors.initials: J
authors.lastname: Vinšová
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007522:Isocitrate Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009161:Mycobacterium / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: C580710:2-methoxy-2'-hydroxybenzanilide; D000813:Anilides; D000970:Antineoplastic Agents; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D007522:Isocitrate Lyase