Isoniazid: Chemical Structure, SAR, Synthesis, Mechanism of Action, Uses & Side effects

Chemical formula:

• C6H7N3O

Structure of Isoniazid

SAR:

• Isoniazid is an antimycobacterial agent used primarily as a tuberculostatic.

• It is an analogue of pyridoxine (vitamin B6), and its activity is related to its structural similarity to this compound.

• Isoniazid inhibits the synthesis of mycolic acid, an essential component of the Mycobacterium cell wall.

• The isonicotinic acid hydrazide moiety is essential for its activity.

Synthesis:

The synthesis of Isoniazid can be conducted as follows:

STEP 1: 4-Cyanopyridine is treated with sodium hypobromite, which undergoes a ring-opening reaction to yield isonicotinic acid:

4-Cyanopyridine + NaOBr → Isonicotinic acid

STEP 2: Isonicotinic acid is then reacted with hydrazine to yield Isoniazid:

Isonicotinic acid + N2H4 → Isoniazid + H2O

Mechanism of action:

• Isoniazid is a prodrug that is activated by the mycobacterial enzyme KatG.

• The activated compound interferes with the synthesis of mycolic acid, a crucial component of the mycobacterial cell wall, thereby inhibiting the growth of Mycobacterium tuberculosis.

Uses:

• Isoniazid is used primarily for the treatment and prevention of tuberculosis (TB).

Side effects:

• Side effects can include hepatotoxicity, peripheral neuropathy, hypersensitivity reactions, and gastrointestinal disturbances.