Antitubercular antibiotics Tuberculosis is caused by either mycobacterium tuberculosis (in Humans) or by mycobacterium bovis (in animals) Tuberculosis is a disease of respiratory transmission. A person gets infected when it comes in contact with the environmental contaminated with viable tubercle Bacilli. This bacilli are expelled by coughing , sneezing , shouting and singing of a patient with active tuberculosis. Tubercles are formed in the infected organs during the course of the disease , hence the disease is known as tuberculosis. Main symptoms are :- cough, tachycardia ,respiratory failure, cynosis (Bluish or greyish colour of the skin, nails, lips or around the eyes.) The agents or antibiotics which are used to treat tuberculosis these are known as the antitubercular antibiotics. Drugs includes :- Rifampicin , streptomycin , cycloserine , capreomycin sulfate and Refabutin Rifampicine Orally active bactericidal semi synthetic derivative of Rifamycin B. This antibiotic is produced by the streptomyces Mediterranei. It is the first line agent. Mechanism of Action :- DNA-dependent-RNA polymerase (DDRP) enzyme is required for the synthesis of RNA. - Rifampicin binds to Beta subunit of enzyme DDRP and make it inactive. - so it causes inhibition of bacterial RNA synthesis. hence there is tuberculocidal effect SAR Free OH group is required at C-1, C-8, C-21, and C- 23 . These group must be in one plane. Opening of ring will destroy the activity of antibiotic. Rifampicin is active against both Gram Negative and Gram Positive Bacteria. resistance is developed when mutation occurs in beta subunit of DDRP. bacterial resistance develop rapidly if rifampicin taken alone, though the combination with Isoniazid or ethambutol are preferable used. Adverse effects : Nausea, Vomiting, headache, erythema, nervousness, emotional disturbances , pulmonary edema, increased cardiac output and cardiac arrythmias

1. Antitubercular antibiotics
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Ganesh Devane

2. Tuberculosis is caused by either mycobacterium tuberculosis
(in Humans) or by mycobacterium bovis (in animals)
• Tuberculosis is a disease of respiratory transmission.
• A person gets infected when it comes in contact with the
environmental contaminated with viable tubercle Bacilli.
• This bacilli are expelled by coughing , sneezing , shouting and singing
of a patient with active tuberculosis.
• Tubercles are formed in the infected organs during the course of the
disease , hence the disease is known as tuberculosis.
• Main symptoms are :- cough, tachycardia ,respiratory failure,
cynosis (Bluish or greyish colour of the skin, nails, lips or around the
eyes.)
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3. • The agents or antibiotics which are used to treat tuberculosis these
are known as the antitubercular antibiotics.
Drugs includes :-
Rifampicin , streptomycin , cycloserine , capreomycin sulfate and
Refabutin
1) Rifampicin
• Orally active bactericidal semi synthetic derivative of Rifamycin B.
• This antibiotic is produced by the streptomyces Mediterranei.
• It is the first line agent.
3

4. Mechanism of Action :-
DNA-dependent-RNA polymerase (DDRP) enzyme is required for the synthesis of RNA.
- Rifampicin binds to Beta subunit of enzyme DDRP and make it inactive.
- so it causes inhibition of bacterial RNA synthesis.
hence there is tuberculocidal effect
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5. SAR :-
• Free OH group is required at C-1,
C-8, C-21, and C- 23 .
• These group must be in one
plane.
• Opening of ring will destroy the
activity of antibiotic.
OH
OH
OH
HO
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6. • Rifampicin is active against both Gram Negative and Gram Positive
Bacteria.
• resistance is developed when mutation occurs in beta subunit of DDRP.
• bacterial resistance develop rapidly if rifampicin taken alone, though the
combination with Isoniazid or ethambutol are preferable used.
• Adverse effects :
Nausea, Vomiting, headache, erythema, nervousness, emotional
disturbances , pulmonary edema, increased cardiac output and cardiac
arrythmias
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7. Streptomycin
• Streptomycin is there aminoglycoside antibiotics which are having in vitro
bactericidal and invivo bacteristatic activity.
• 1st clinically effective anti tuberculosis agent.
• Usually available as the
trihydrochloride.
• Both are quite Soluble in water.
α Streptose
Streptidine
Streptobiosamine
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8. Mechanism Of Action :
• Streptomycin binds to 16s ribosomal DNA portion of 30s ribosomal sub
particles ,imparing true reading function of ribosomes.
• It causes misreading of the genetic code and thus affects translation
process.
• By misreading of mRNA template there is attachment of incorrect amino
acid and hence formation of nonsence protein.
• This nonsense protein will disturb bacterial membrane function and will
destroy semipermeable membrane which is non recoverable.
• this affect the growth and multiplication of bacteria Cell will stop.
• ( Bactericidal action )
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9. SAR :
• The reduction of the aldehyde to alcohol at the α Streptose portion
of streptomycin it will increases the potential of bactericidal action.
E.g. Dihydrostreptomycin.
• Oxidation of aldehyde to a Carboxylic group decreases the activity.
there is formation of inactive analogue.
• modification of guanidine in the streptidine nucleus also decrease
the activity.
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10. Adverse effects :-
• it may causes nephrotoxicity, ototoxicity and blood dyscrasias in
patient.
• adverse effect of streptomycin is depends on dose and duration
of treatment.
• Streptomycin resistant strains are usually treated with
kanamycin.
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11. Cycloserine :-
•It is an analogue of D-alanine having broad-spectrum
antimicrobial profile.
• It inhibit both gram Negative and gram Positive bacteria.
• Cycloserine is isolated from Streptomyces Orchidaceus.
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12. Mechanism Of Action :
• D- cycloserine is active form of drug. Which have the ability to inhibit two
key enzymes.
• D-alanime racemase and D-alanine ligase.
• D-alanime is an important component of peptidoglycan portion of the
mycobacterial cell wall.
• L-alanine is converted into D-alanine with the help of D-alanine recemase.
• The D-alanine is coupled with itself to form D-alanine complex in the
presence of D-alanine ligase.
• This complex of D-alanine then incorporated into the cell wall of
micobacteria.
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13. • By blocking the enzyme the cell wall synthesis stoped and hence
bactericidal activity
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D alanine recemase D-alanine ligase

14. Adverse effects :-
Headche, visual disturbances, nervousness, irritability, depression,
confusion, tremors .
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15. Capreomycin :
• it is the second line agent.
• these agent give with combination when the resistance developed by
bacteria to first line drugs .
• it is the mixture of Four cyclic polypeptide IA, IB, IIA, IIB.
• IA is (R= OH)
• IB is ( R=H)
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16. Mechanism Of Action :
•It binds to both 30s and 50s ribosomal subunit resulting
into inhibition of bacterial protein synthesis .
Use :- capreomycin is mainly used in combination with
Ethionamide or Ethambutol against Streptomycin resistant
strain .
•Injections of these drugs are painful.
Adverse effects :- Skin rashes, fever, Otoxicity
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17. Referance :-
• Principles of Medicinal Chemistry. (By Dr. S. S. Kadam, Dr. K. R.
Mahadik, Dr. K. G. Bothra) . (Volume I)
• Chapter 36 , Page no. 1185 , 1187 , 1188 , FOYE’S Principles of
Medicinal Chemistry , SEVENTH EDITION