Classification of antitubercular drugs

Antitubercular drugs are used to treat tuberculosis (TB), a bacterial infection caused by Mycobacterium tuberculosis. These drugs are classified into first-line and second-line categories based on their efficacy, use in treatment regimens, and side effects.

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First-Line Antitubercular Drugs

These are the primary drugs used in the treatment of TB due to their effectiveness and safety profile.

Isoniazid (INH): Inhibits mycolic acid synthesis in the bacterial cell wall.

Chemical Formula: C6H7N50

Rifampin (RIF): Inhibits bacterial RNA polymerase.

Chemical Formula: C43H58N4012

Ethambutol (EMB): Inhibits cell wall synthesis by interfering with arabinogalactan synthesis.

Chemical Formula: C10H15NO2

Pyrazinamide (PZA): The exact mechanism is unknown, but it is thought to disrupt membrane potential and energy production.

Chemical Formula: CSH5N30

Second-Line Antitubercular Drugs

These drugs are used when first-line drugs fail or for multi-drug-resistant TB.

Streptomycin (SM): An aminoglycoside antibiotic that inhibits protein synthesis.

Chemical Formula: C21H39N7012

Kanamycin: An aminoglycoside antibiotic similar to streptomycin.

Chemical Formula: C18H36N4011

Capreomycin: A peptide antibiotic that inhibits protein synthesis.

Chemical Formula: C62H106N18022

Ethionamide: Similar in structure to INH and inhibits mycolic acid synthesis.

Chemical Formula: C8H10N2S

Cycloserine: Inhibits cell wall synthesis by mimicking D-alanine.

Chemical Formula: C3H4N202

Synthesis of Isoniazid (INH)

Isoniazid is a key first-line drug for tuberculosis. Its synthesis involves the following steps:

Starting Material: Hydrazine

Chemical Formula: N2H4

Formation of Isonicotinic Acid Hydrazide:

Reaction: Hydrazine reacts with isonicotinic acid to form isoniazid. This is typically done by first converting isonicotinic acid to isonicotinoyl chloride using thionyl chloride (SOCI2) and then reacting it with hydrazine.

Reagents: Isonicotinic acid, thionyl chloride (SOCI2), and hydrazine.

Reaction:

where isonicotinic acid is C6HS5NO2.

Conversion to Isoniazid:

Reaction: The hydrazide form is obtained from the hydrazone intermediate.

Isoniazid (INH) is synthesized from hydrazine and isonicotinic acid via an intermediate hydrazide. This process typically involves converting isonicotinic acid to its chloride form and then reacting it with hydrazine to form isoniazid.

Antitubercular drugs are classified into first-line drugs (e.g., isoniazid, rifampin) used as primary treatment and second-line drugs (e.g., streptomycin, kanamycin) used for resistant cases or when first-line drugs are ineffective.