ANTILEPROTIC

DRUGS

BY :
ACHSAH
B
PHARMACY
 INTRODUCTION
Leprosy is a chronic infectious disease caused by
Mycobacterium leprae ( M.laprae), acid fast bacilli.
Also known as Hansen’s disease, after the scientist who
discovered M.leprae in 1873 – Dr.Gerhard Henrik Armauer
Hansen of Norway.
It’s a slow growing bacteria as it needs long incubation
period (3-5 years )
Curable now
EFFECTS – SKIN, MUCOUS MEMBRANE AND
PERIPHERAL NERVES.
 TYPES OF LEPROSY
2 TYPES OF LEPROSY:
PAUCIBACILLARY LEPROSY(PBL) OR TUBERCULOID
LEPROSY
MULTIBACILLARY LEPROSY (MBL) OR LEPROMATOUS
LEPROSY

PAUCIBACILLARY – The cell mediated immunity is intact ,

single or few lesions ,the bacilli are rarely seen and very little
chance of infection .
MULTIBACILLARY- The cell mediated immunity is impaired
against the leprae bacilli, more than 5 lesions, more chance of
infection.
 CLASSIFICATION
Anciently used CHAULMOORGRA OIL AND HYDNOCARPOUS OILS.
1940 ONWARDS Discovery of sulphonamides .

1. SULPHONES- DAPSONE (DDS)

2.PHENAZINE DERIVATIVE- CLOFAZIMINE

3.ANTITUBERCULAR DRUGS – RIFAMPICIN , ETHIONAMIDE

4.OTHER ANTIBIOTICS – OFLOXACIN,MOXIFLOXACIN,
MINOCYCLINE AND CLARITHROMYCIN
FOLATE SYNTHETASE

Sulphonamide similar to
PABA

Sulphonamide

Similar
to
 FOLATE
DAPSONE SYNTHETASE

THIMIDINE DNA
 DAPSONE (DDS)
Dapsone or diaminodiphenylsulphone (DDS):
Dapsone a sulphone , is the oldest , cheapest and most widely used
agent for the treatment of leprosy even today.

MECHANISM OF ACTION
Sulphones are chemically related to sulphonamides and have
same mechanism of action.
Leprae bacilli utilize para- aminobenzoic acid (PABA) for the
synthesis of folic acid which is necessary for the growth and
multiplication of the bacteria.
Dapsone similar to PABA structurally , inhibits folate synthetase
enzyme and prevents the formation of THFA( TETRA
HYDROFOLIC ACID).
Produce leprostatic effect.
 MECHANISM OF
ACTION
CLOFAZIMINE
The molecule possess direct antimycobacterial
properties.It has been shown that clofazmine inhibits
the prostaglandin synthesis(antiinflamatory effect)
and generation of antimycobacterial reactive
oxidants from neutrophils (enhancement of
immunity)which can play a important role in the
antileprosy effects.The host cell defence can be
stimulated by clofazimine resulting in the generation
of oxidants such as superoxide anion which in turn
could have lethal effects on the organism.
SYNTHESIS OF DAPSONE
 ADVERSE EFFECTS OF DAPSONE
•Anaemia
•Nausea
•Vomiting
•Fever
•Headache
•Gastric irritation
•Itching

SULPHONE SYNDROME

Dapsone may cause exacerbation of lesions , characterised by

fever, priritus, and anaemia .
 SAR OF
DAPSONE
Substitution of CH2SO2Na( methane sulfinate ) for R gave Sulfoxone
sodium , a prodrug of dapsone . The amount of sulfoxone is thrice that of
dapsone . This is given to patients having GIT irritation induced by dapsone.

When the phenyl ring of dapsone was substituted with suitable groups
eg sulfacetamide, the derivatives possessed less activity than the parent
drug eg. Acetosulfone
 Cont. of SAR

Acedapsone a prodrug of dapsone R= -COCH3. This derivative is

released very slowly than the parent drug .

When benzene ring of dapsone was replaced with thiazole ring

Thiazole sulfone was obtained which is less reactive than dapsone .
 SAR OF CLOFAZIMINE
The chemical phenazine nucleus is essential for
antimycobacterial property.

Substitution of imino group on position 11 is essential for

the activity . The imino group substituted with cycloalkyl or
alkyl groups increases the activity.
 SAR CONT.

The halogen substitution at para position of 2 phenyl rings

at position C-12 and N-4 enhance the activity .
Following order of activity has been reported
Br>Cl> CH3 >H or F
THAN
K YOU