antitubercular agents medicinal chemistry according to pci syllabus

1. Antitubercular Agents

2. • These are the drugs used for the treatment of
tuberculosis
• Tuberculosis is the most prevalent infectious
diseases caused by mycobacterium
tuberculosis
• The common infectious sites are lungs,bone
,brain, liver and kidney

3. • Treatment First line drugs
• First-line drugs: Isoniazid, streptomycin,
rifampicin, ethambutol, and pyrazinamide
• Second-line drugs: Ethionamide, p-amino
salicylic acid, ofl oxacin, ciprofl oxacin,
cycloserine, amikacin, kanamycin, viomycin,
and capreomycin.

4. The majority of the patients with tuberculosis are treated with
first-line drugs and shows excellent results with a 6-month course
of treatment. For the first 2 months, isoniazid, rifampicin, and
pyrazinamide are given, followed by isoniazid and rifampicin for
the remaining 4 months.
Second-line drugs are used mainly to treat multidrug resistant M.
tuberculosis infections

5. • Isoniazid

7. Mode of action: Isoniazid is a prodrug that is activated on
the surface of M. tuberculosis by katG enzyme to
isonicotinic acid. Isonicotinic acid inhibits the bacterial cell
wall mycolic acid, thereby making M. tuberculosis
susceptible to reactive oxygen radicals. Isoniazid may be
bacteriostatic or bactericidal in action, depending on the
concentration of the drug attained at the site of infection
and the susceptibility of the infecting organism

10. Mode of action: Aminosalicylic acid is an inhibitor of bacterial folate metabolism
in a manner similar to the sulphonamide antibacterials

12. Mode of action: It is a bacteriostatic drug that inhibits the incorporation of mycolic
acid into the mycobacterium cell wall

13. The first-line antibiotic drug ethambutol (EMB) interferes with cell wall
biosynthesis in Mycobacterium tuberculosis. EMB inhibits the action of
arabinosyl transferase (EmbB).
EmbB is a membrane-associated enzyme involved in the synthesis of
arabinogalactan. Arabinogalactan is an essential structural component of
the mycobacterial cell wall.

15. Mode of action:
The first-line antibiotic drug pyrazinamide (PZN) interferes with
cell wall biosynthesis in Mycobacterium tuberculosis. PZN is a
prodrug and is converted to an active form (pyrazinoic acid) by
a nicotinamidase-peroxidase enzyme known as pyrazinamidase
(PncA).
Pyrazinoic acid inhibits the action of fatty acid synthetase I
(FAT-I). FAT-I is involved in the synthesis of short-chain mycolic
acids. Mycolic acids are essential structural components of the
mycobacterial cell wall and are attached to the arabinogalactan
layer.

16. Mode of action: The second-line antibiotic drug ethionamide (ETH) interferes
with cell wall biosynthesis in Mycobacterium tuberculosis. ETH is a prodrug and
is converted to an active form by monooxygenase (EthA). Similar to Isoniazid
(INH), ETH also inhibits the action of enoyl-acyl carrier protein reductase (InhA).
InhA is an important enzyme component of the fatty acid synthetase II (FAS-II)
complex. FAS-II is involved in the synthesis of long-chain mycolic acids. Mycolic
acids are essential structural components of the mycobacterial cell wall and are
attached to the arabinogalactan layer.

19. Mode of action: It is an antibiotic obtained from Streptomyces mediterranei.
Rifampicin binds to the b-subunit of the DNA-dependent RNA polymerase
enzyme complex and inhibits transcription of messenger RNA (mRNA). The
mRNA transcripts are essential requirements for protein synthesis (translation).

20. Rifabutin
It is a semisynthetic rifamycin, structurally similar to rifampicin. It is used against M.
avium, one of the most common causes of disseminated infections, with patients
suffering with Human Immunodeficiency Virus (HIV). In vitro activity is attributed to
rifabutin’s lipophilic nature and its ability to penetrate the cell wall of the organism more
effectively than other agents.

21. cycloserine
Mode of action: The second-line antibiotic drug D-cycloserine (DCS) is a
substrate analogue of D-alanine and interferes with cell wall biosynthesis in
Mycobacterium tuberculosis. DCS is a competitive substrate inhibitor of D-
alanine racemase (Alr) that converts L-alanine to D-alanine and D-alanyl-D-
alanine synthetase (Ddl) that synthesises D-alanyl-D-alanine dipeptides from D-
alanine. The D-alanyl-D-alanine dipeptides are important precursor molecules
required for the synthesis of peptidoglycan. Peptidoglycan is an essential
structural component of the mycobacterial cell wall.

23. capreomycin sulphate
Capreomycin (CAP) are peptides that also interfere with translation. These
drugs bind to the 30S subunit of the ribosome complex and inhibit the
synthesis of mycobacterial proteins