Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for leprosy treatment. It was independently discovered in the 1930s-1940s and acts as an antibacterial by inhibiting the synthesis of dihydrofolic acid. Common adverse effects include mild haemolytic anaemia, gastric intolerance, and methaemoglobinaemia. Dapsone's mechanism of action involves inhibiting the enzyme dihydropteroate synthetase to block bacterial folic acid synthesis, and it may also have an anti-inflammatory effect through an unknown mechanism.

1. Sulphones
By
Gunjan Kalyani, M.Pharm.
Assistant Professor
Columbia Institute of Pharmacy
Raipur 493111, Chhattisgarh, India
Mobile: +91-8349204583
Mail ID: kalyani.gunjan@yahoo.in
Former Research Fellow
National Center for Natural Resources (NCNR)
Pt. Ravishankar Shukla University, Raipur 492010, India

2. Sulphones

3. A. In the early 20th century, the German chemist Paul Ehrlich
was developing theories of selective toxicity based largely
on the ability of certain dyes to kill microbes.
B. Gerhard Domagk, who would later win a Nobel Prize for his
efforts, made a major breakthrough in 1932 with the
discovery of the antibacterial prontosil red
(sulfonamidochrysoidine).
C. Further investigation into the involved chemicals opened the
way to sulfa drug and sulfone therapy, first with the
discovery of sulfanilamide, the active agent of prontosil, by
Daniel Bovet and his team at Pasteur Institute(1935).
History

4. D. Then with of Dapsone independently by Ernest Fourneau
in France and Gladwin Buttle in United Kingdom.
E. Dapsone (diamino-diphenyl sulfone) is a medication most
commonly used in combination with rifampicin and
clofazimine as multidrug therapy (MDT) for the
treatmentof Mycobacterium leprae infections (leprosy).
F. Official in IP, BPandUSP.
History

5. 4,4’-diaminodiphenylsulfone
Structure and IUPAC
Name

6. Introduction
A. Sulfones are one of the members of organo sulfur
compounds.
B. Sulfones are S, S-dioxides of ether and represented by
general structural formula R-S(O)2-R’, where R and R’
are organic groups.
C. The chemistry of sulfones has been explored due to
their importance as synthetic intermediates for the
production of a wide range of chemically and
biologically active molecules.
D. Sulfones are widely used as solvents, polymers, and
biopharmaceutical agents.

7. E. Several drug molecules containing sulfone groups are
used for the treatment of leprosy, dermatitis
herpetiformis, and tuberculosis.
F. Researchers have also determined many therapeutic
activities of sulfone containing compounds, including
antibacterial, antifungal, antimalarial, cysteine protease
inhibitor, anti-HIV, anti-proliferative, anti-cancer,
protein phosphatase methylesterase-1 inhibitors, thyroid
receptor antagonist, β-lactamase inhibitors and
gelatinase inhibitors.
Introduction

8. Substitution of aromatic ring with
acetyl group results in decreased
activity, increased solubility in water
and decreased G.I irritation.
Replacement of 1 amino group with
nitro, hydroxy or hydroxylamine
results in decreasedactivity.
Replacement of both amino groups
gives inactive product(with above).
Structure Activity relationship

9. Replacement of one of benzene
rings with thiazole resulted in
decreased activity.
Replacement of both amino
groups with aldehyde results in
prodrugformation (eg.
glucosulfone sodium).
Structure Activity
relationship

10. Synthesis of Dapsone

11. Mechanism of Action
A. Dapsone acts against bacteria and protozoa in the
same way as sulphonamides, that is by inhibiting the
synthesis of dihydrofolic acid through competition
with para-amino-benzoate for the active site of
dihydropteroate synthetase.
B. The anti-inflammatory action of the drug is unrelated
to its antibacterial action and is still not fully
understood.

12. Mechanism of Action

13. A. Mild haemolyticanaemia
B. Gastric intolerance nausea
andanorexia
C. Methaemoglobinaemia
D. Headache
E. Paresthesias
F. Mental symptoms & drug
fever
G. Hepatitis and
Agranulocytosis
H. Allergic rashes
I. Fixeddrug eruption
J. Hypermelanosis
K. Phototoxicity
L. Rarely exfoliativedermatitis
M. Dapsonereaction
N. sulfone syndrome
Adverse Effects

14. A. Hypersensitivity is more frequent in patients receiving
multiple drug therapy.
B. The reaction involves a rash and may also include fever,
jaundice,and eosinophilia.
C. In general, these symptoms will occur within the first six
weeks of therapy or not at all, and may be treated by
corticosteroid therapy.
Dapsone reaction

15. A. Mycobacteriumleprae infections (leprosy).
B. Hansen’s disease
C. Acne.
D. Pneumocystispneumonia
E. DermatitisHerpetiformis
F. Toxoplasmosis- Prophylaxis
Uses

16. Drug Interactions
A. Before using this medication, consult with your doctor
or pharmacist of all prescription and non
prescription/herbal products you may use, especially
of: folic acid antagonists (such as pyrimethamine),
nitrofurantoin, primaquine.
B. This medication may decrease the effectiveness of
combination-type birth control pills.
C. This can result in pregnancy.

17. Recent development
A. The need for a more reliable route of administration led
to investigation the possibility of an I.M. dapsone depot
injection.
B. To achieve effective blood levels for 3-4 weeks, suspensions
of large dapsone particles in anaqueous vehicle were made.
C. Studies in the rat revealed that dapsone-dependent
methaemoglobinaemia could be greatly diminished by the
co-administration of metabolicinhibitors (eg- cimetidine).

18. D. The need for a more reliable route of administration
ledto investigation the possibility of an I.M. dapsone
depot injection.
E. To achieve effective blood levels for 3-4 weeks,
suspensions of large dapsone particles in an aqueous
vehicle were made.
F. Studies in the rat revealed that dapsone-dependent
methaemoglobinaemia could be greatly diminished by
the co-administration of metabolic inhibitors (eg-
cimetidine).
Recent development

19. 1. Williams D.et al, Foye's principles of medicinal
chemistry, fifth edition, Lippincott's Williams &
Wilkins
2. John H.et al ,Wilson & Gisvolds textbook of organic medical
& pharmaceutical chemistry, eleventh edition, Lippincott's
Williams & Wilkins
3. Indian Pharmacopoeia, 1996,Volume I, 1162-1163
4. United states Pharmacopoeia,2009,Volume II, 2059-2060
5. Moncrief J. Journal of Chromatography B: Biomedical
Sciences and Applications
Volume 654, Issue 1, 18 March 1994,103:110.
7. http://www.rxlist.com
8. http:// www.medicinenet.com
9. http://www.leprosy-information.org
10. http://onlinelibrary.wiley.com
References

20. Acknowledgements
A. D.A.V. Public School, ACC Colony, Jamul – 490024, Durg, Chhattigarh, India (1990 – 2004)
B. University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India (2005 –
2009)
C. Shri Rawatpura Sarkar Institute of Pharmacy, Kumhari, Durg, Chhattisgarh, India (2010 – 2012)
D. Royal College of Pharmacy, Raipur, Chhattisgarh, India (March – October 2013)
E. National Center for Natural Resources (NCNR), Pt. Ravishankar Shukla University, Raipur, Chhattisgarh,
India (2013 – 2017)
F. Columbia Institute of Pharmacy, Raipur 493111, Chhattisgarh, India ( 2017 – till date)
G. Gratitude to Resp. Prof. Shiv Shankar Shukla Sir, Columbia Institute of Pharmacy, Raipur 493111,
Chhattisgarh, India (Mentor)
H. Gratitude to Resp. Prof. Atanu Kumar Pati Sir, Vice Chancellor, Gangadhar Meher University, Sambalpur,
Odisha
I. Gratitude to Resp. Prof. Mitashree Mitra Madam, Dept. of Anthropology, PRSU, Raipur, Chhattisgarh.
J. Gratitude to Resp. Vishal S. Deshmukh Sir (M.Pharm. Supervisor)

21. Q & A Time!

22. 1. Discuss the chemistry of dapsone with historical
development (5 marks).
2. Discuss the SAR of Dapsone (5 marks).
3. Write the synthesis of Dapsone along with some
adverse effects associated with it (5 marks).
4. Discuss about mechanism of action of Sulphones. Write
about the Dapsone syndrome (5 marks).
Q & A Time!

23. Thanks for studying !!!!