Synthesis and in vitro antimycobacterial activity of 2-methoxybenzanilides and their thioxo analogues.
A new series of N-(3/4-substituted phenyl) 4/5-chloro-2-methoxybenzamides and their thioxo analogues have been synthesised and evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, as well as the two atypical strains Mycobacterium kansasii and Mycobacterium avium. Five of the most active compounds were evaluated for cytotoxicity and their ability to inhibit mycobacterial isocitrate lyase, which is responsible for latent survival of Mycobacterium. The results showed that benzthioanilides were more active than the corresponding benzanilides. The most active compound, 4-chloro-2-methoxy-N-(3,4-dichlorophenyl)benzothioamide (4e), had a minimal inhibition concentration (MIC) against M. tuberculosis of 2 μmol L(-1), which was better than the activity of the previously published corresponding salicylanilide.
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Inorganic and Organic Chemistry, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Ján
J
Kozic
Eva
E
Novotná
Marie
M
Volková
Jiřina
J
Stolaříková
František
F
Trejtnar
Jarmila
J
Vinšová
D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / 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; D009162:Mycobacterium avium / Q000187:drug effects*; D019909:Mycobacterium kansasii / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000813:Anilides; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007522:Isocitrate Lyase