Chemical formula:
C12H12N2O2S
Mechanism of action:
Dapsone's exact mechanism of action is not fully understood, but it is believed to interfere with bacterial folic acid synthesis by competing with para-aminobenzoic acid (PABA) for the active site of dihydropteroate synthase. This inhibition leads to a disruption of bacterial DNA synthesis and ultimately cell death.
Structure-Activity Relationship (SAR) of Dapsone:
1.Sulfone Group:
The key feature of dapsone's structure is its sulfone group (-SO₂-). This group is crucial for its antimicrobial and anti-inflammatory activities.
2.Aromatic Amines:
Dapsone contains two aromatic amine groups. These groups are essential for the drug's therapeutic effects, as they are believed to interfere with bacterial folic acid synthesis, similar to sulfonamides.
3.Lipophilicity:
The overall lipophilic nature of dapsone, due to its aromatic rings, influences its absorption and distribution in the body. The balance between lipophilicity and solubility is important for its effectiveness.
4.Stability of the Sulfone Group:
The chemical stability of the sulfone group in dapsone is crucial for its long half-life and sustained therapeutic action.
Synthesis of Dapsone:
The synthesis of Dapsone typically involves the following steps:
1.Synthesis of 4-Nitroaniline:
One starting material is 4-nitroaniline, which can be synthesized through the nitration of aniline:
Aniline + Nitration Reagents → 4-NitroanilineAniline
2.Diazotization and Coupling:
The 4-nitroaniline is then diazotized (conversion into a diazonium compound) and coupled with another aromatic compound. This step is crucial for introducing the sulfone group:
4-Nitroaniline → Diazonium Salt → Intermediate
3.Reduction and Sulfonation:
The intermediate is then reduced (to remove the nitro group) and subsequently sulfonated to introduce the sulfone group:
Intermediate → Amine → Dapsone
Uses:
Dapsone is primarily used in the treatment of leprosy as a part of multidrug therapy (MDT) along with rifampicin and clofazimine. It is also used for the treatment of dermatitis herpetiformis, a chronic autoimmune skin disorder, and as a second-line treatment for Pneumocystis jiroveci pneumonia in patients who are intolerant to or unresponsive to co-trimoxazole (sulfamethoxazole and trimethoprim).
Side effects:
Common side effects of dapsone include gastrointestinal disturbances (nausea, vomiting, diarrhea), headache, and dizziness. Less common side effects include methemoglobinemia (a condition where hemoglobin is unable to release oxygen to tissues), hemolytic anemia (especially in individuals with glucose-6-phosphate dehydrogenase deficiency), and agranulocytosis (a severe decrease in white blood cells). Skin reactions such as rash and photosensitivity may also occur.