Antileprosy agents.pdf, Introduction and Classification

Antileprosy agents.pdf, Introduction, Classification, SAR and MOA

1. Antileprosy agents
Prepared by
Dr. Girish Kashid
Asst. Prof.
Sanjivani College of Pharmaceutical
Education & Research
Prepared by- Dr. Kashid Girish, SCPER

2. Prepared by- Dr. Kashid Girish, SCPER
Mycobacterium
- Mycobacteria are designated as the transition forms existing between bacteria
and fungi.
-The Greek prefix “myco” - means "fungus" alluding to the way mycobacteria
have been observed to grow in a mold-like fashion on the surface of cultures.
-It has a positive gram stain and a spirochete spine.
- Mycobacterium refers to a genus of acid-fast organisms.
- Mycobacteria are aerobic and non-motile bacteria.
- Mycobacterium is a genus of Actinobacteria, given its own family, the
Mycobacteriaceae. This genus includes pathogens known to cause serious
diseases in mammals, including tuberculosis (Mycobacterium tuberculosis) and
leprosy (Mycobacterium leprae) in humans.
Alluding : सूचित

3. Prepared by- Dr. Kashid Girish, SCPER

4. Prepared by- Dr. Kashid Girish, SCPER
Cell wall
structure of
mycobacterium

5. Prepared by- Dr. Kashid Girish, SCPER
Leprosy (Hansen’s disease)
Chronic granulomatous infection caused by Mycobacterium leprae
Mainly affects
✓ Skin
✓ Peripheral nerves
✓ Upper respiratory tract
✓ Eyes
✓ Testes
Seen mainly in developing countries
60% of total patients are in India Bimodal age distribution
First peak : 10 to 14 years
Second peak : 35 to 44 years

6. Classification
1.Sulfone Dapsone (DDS)
2.Phenazine derivative Clofazimine
3.Antitubercular drugs Rifampin,
Rifamycin
4.Other antibiotics Minocycline,
Clarithromycin
5.Miscellaneous Thalidomide (Thalomid)
Prepared by- Dr. Kashid Girish, SCPER

7. Prepared by- Dr. Kashid Girish, SCPER
1.Sulfone Dapsone (DDS)
Sulfones
The diaryl sulfones represent the major class of agents used to treat leprosy.
Dapsone was first introduced into the treatment of leprosy in 1943.
MECHANISM OF ACTION
Dapsone, a bacteriostatic agent, is thought to act
in a manner similar to that of the
sulfonamides— namely, through competitive
inhibition of p-aminobenzoic acid incorporation
into folic acid

8. Prepared by- Dr. Kashid Girish, SCPER
STRUCTURE–ACTIVITY RELATIONSHIP
➢Isosteric replacement of one benzene ring resulted in the formation of
thiazolsulfone. Although still active, it is less effective than dapsone.
➢Substitution on the aromatic ring, to produce acetosulfone, reduced activity
while increasing water solubility and decreasing GI irritation.
➢A successful substitution consists of adding methanesulfinate to dapsone to give
sulfoxone sodium.

9. Prepared by- Dr. Kashid Girish, SCPER
2.Phenazine derivative Clofazimine
Clofazimine
MECHANISM OF ACTION
It is a dye with leprostatic and anti-inflammatory
properties.
The putative mechanisms of antileprotic action of
clofazimine are:
• Interference with template function of DNA in
M.leprae
• Alteration of membrane structure and its transport
function.
• Disruption of mitochondrial electron transport chain.
Putative : म ांडणी

10. Prepared by- Dr. Kashid Girish, SCPER
❖STRUCTURE–ACTIVITY RELATIONSHIP
❖Substituents on the imino group at position 2, p-chloro substitution on the
phenyls at C-3 and N-10, and substituents at position 7 have been
investigated. The imino group at C-2 appears to be essential, with activity
increased when the imino group is substituted with alkyl and cycloalkyl
groups.
❖Halogen substitution on the para position of the two phenyls at C-3 and N-10
enhance activity but are not essential to activity.
❖The following order of activity has been reported: Br > Cl > CH3 > EtO > H
or F.
❖In the analogs studied, the increased activity correlates well with pro-
oxidative activities of the molecule (e.g., ability to generate superoxide anion)
as well as increased lipophilicity.

11. Prepared by- Dr. Kashid Girish, SCPER
3.Antitubercular drugs Rifampin,
Ethionamide
4.Other antibiotics Minocycline,
Clarithromycin

12. Prepared by- Dr. Kashid Girish, SCPER
5.Miscellaneous Thalidomide (Thalomid)
This condition has been successfully treated
with thalidomide. Recently, thalidomide has
been approved by the FDA for treatment of ENL
and is considered to be the drug of choice
(ENL): erythema nodosum leprosum