Isoniazid antibacterial activity

Substitution of an amino group into the molecule affords an iigent with antibacterial activity. Although seldom used alone, l, ira- aminosalicylic acid (PAS, 7) has been employed as an adjunct Id streptomycin and isoniazid in treatment of tuberculosis. 

Direct InhA inhibitors have also been sought to avoid isoniazid resistance mediated by catalase-peroxidase mutation. Lipophilic analogs of triclosan such as 36 show a nanomolar K on the enzyme with an MIC of 1-2 pg/mL on isoniazid-resistant strains [56]. Structure-based optimization of two separate HTS leads afforded 37 and 38, both submicromolar inhibitors of InhA but devoid of any significant antibacterial activity [57,58],... 

Simple substituted pyridines such as isoniazid (7) showed antibacterial activity. The structurally related ethionamide (8) is an active antibiotic prodrug against tuberculosis in humans. Nicotine (1) and epibatidine (9) are naturally occurring agonists of neural nicotinic acetylcholine receptors... 

On the other hand, NAD (nicotinamide adenine dinucleotide), known as coenzyme I and II, and NADP (nicotinamide adenine dinucleotide phosphate) are derivatives of nicotinamides. The chemical structures of NAD, NADP, and the reduced form of these alkaloids, NADH and NADPH (nicotinamide adenine dinucleotide phosphate reduced), are shown. Isonicotinic acid hydrazide (INH or isoniazid) is a synthetic derivative of nicotinic acid and has potent antibacterial activity against Mycobacterium tuberculosis (Section 13.2) [1,2]. 

Acnisal salicylic acid, aconiazide [inn] is an isoniazid analogue and an ANTITUBERCULAR and ANTIBACTERIAL AGENT, aconitine is an alkaloid from monk s hood or wolfsbane (Aconitum napellus) and other Aconltum spp. (Ranunculaceae). It is a NEUROTOXiN implicated in poisoning by A. spp., especially, 4. chasmanthum in India. Experimentally, it is a SODIUM-CHANNEL ACTIVATOR that binds to Na -channels, slows inactivation, shifts inactivation to a more negative value, and alters ion specificity. This results in repetitive firing of neurons, with marked effects on the heart including positive inotropism and arrhythmias. Aconitine (and the related alkaloid delphinine) were formerly used in... 

As synthesis intermediates are chemically connected to final products, and as they often present some common groupings with them, it is not inconceivable that they share some pharmacological properties. For this reason, it is always prudent also to submit these compounds to a pharmacological evaluation. Among drugs discovered in this way are the tuberculostatic semicarbazones they were initially used in the synthesis of antibacterial sulfathiazoles. Subsequent testing of isonicotinic acid hydrazide, destined for the synthesis of a particular thiosemicarbazone, revealed the powerful tuberculostatic activity of the precursor which has since become a major antitubercular drug (isoniazide). 

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