生物活性

• 描述Isonicotinic acid hydrazide (INH) is a synthetic antibiotic used for the treatment of tuberculosis. Isoniazid has outstanding bactericidal action against M. tuberculosis with a minimal inhibitory concentration of 0.1 – 0.7 µM. The treatment of 100 µM INH in an human granuloma model significantly reduced bacterial growth 6 days after the infection. However, INH-induced mycobactericidal activity was not altered when granuloma-like structures were depleted from CD3⁺ T cells. When P. berghei-infected mice were treated with 25 or 50 mg/kg INH intraperitoneally and fed to An. stephensi mosquitoes, the exflagellation level in mosquito gut was significantly reduced, as well as the number of oocyst per gut, indicating decreased parasite development by INH treatment. Dose-response curve showed that INH dose (10 – 150 mg/kg) was positively correlated with its transmission-blocking effect in P. berghei/mouse model, and the half-maximal effective dose of INH was 109 mg/kg.
• 作用机制Isonicotinic acid hydrazide (INH) passively enters mycobacterial cell through the cell wall and is activated by a mycobacterial enzyme called KatG. Activated IHN led to the accumulation of reactive oxygen species. The produced isonicotinoyl radical binds to a NAD molecule, resulting in the inhibition of FASII enoyl-ACP reductase InhA, which is essential in the mycolic acid biosynthesis pathway. The inhibition impedes cell wall synthesis, and eventually leads to cell death.

• 动物研究
  剂量	Rat: 0.05 g/kg[3] (s.c.)
  给药途径	s.c.