The sulfones are primarily of interest as antibacterial agents, though there are some reports of their use in the treatment of malarial and rickettsial infections. They are less effective than the sulfonamides. PABA partially antagonizes the action of many of the sulfones, suggesting that the mechanism of action is similar to that of the sulfonamides. Further, infections that arise in patients being treated with sulfones are cross-resistant to sulfonamides. Several sulfones have proved useful in the treatment of leprosy, but among them only dapsone is clinically used today.
It has been estimated that there are about 11 million cases of leprosy in the world, of which about 60% are in Asia (with 3.5 million in India alone). The first reports of dapsone resistance prompted the use of multidrug therapy with dapsone, rifampin, and clofazimine combinations in some geographic areas.128
The search for antileprotic drugs has been hampered by the inability to cultivate M. leprae in artificial media and by the lack of experimental animals susceptible to human leprosy. A method of isolating and growing M. leprae in the footpads of mice and in armadillos has been reported and has permitted a much wider range of research. Sulfones were introduced into the treatment of leprosy after it was found that sodium glucosulfone was effective in experimental tuberculosis in guinea pigs.
The parent sulfone, dapsone (4,4'-sulfonyldianiline), is the prototype for various analogs that have been widely studied. Four variations on this structure have given active compounds:
1. Substitution on both the 4- and 4'-amino functions
2. Monosubstitution on only one of the amino functions
3. Nuclear substitution on one of the benzenoid rings
4. Replacement of one of the phenyl rings with a hetero-
The antibacterial activity and the toxicity of the disubsti-tuted sulfones are thought to be chiefly caused by the formation in vivo of dapsone. Hydrolysis of disubstituted derivatives to the parent sulfone apparently occurs readily in the acid medium of the stomach but only to a very limited extent following parenteral administration. Monosubstituted and nuclear-substituted derivatives are believed to act as entire molecules.
Dapsone (4,4'-sulfonylbisbenzeneamine; 4,4'-sulfonyldian-iline; p,p'-diaminodiphenylsulfone; or DDS [Avlosulfon]) occurs as an odorless, white crystalline powder that is very slightly soluble in water and sparingly soluble in alcohol. The pure compound is light stable, but traces of impurities, including water, make it photosensitive and thus susceptible to discoloration in light. Although no chemical change is detectable following discoloration, the drug should be protected from light.
Dapsone is used in the treatment of both lepromatous and tuberculoid types of leprosy. Dapsone is used widely for all forms of leprosy, often in combination with clofazimine and rifampin. Initial treatment often includes rifampin with dapsone, followed by dapsone alone. It is also used to prevent the occurrence of multibacillary leprosy when given pro-phylactically.
Dapsone is also the drug of choice for dermatitis herpetiformis and is sometimes used with pyrimethamine for treatment of malaria and with trimethoprim for PCP.
Serious side effects can include hemolytic anemia, methemoglobinemia, and toxic hepatic effects. Hemolytic effects can be pronounced in patients with glucose-6-phos-phate dehydrogenase deficiency. During therapy, all patients require frequent blood counts.
1. What is the definition of an antiseptic?
2. What happens to the antimicrobial activity of alcohols as the carbon chain becomes more branched?
3. What kind of bond associates iodine with polyvinylpyrrolidone in PVP-iodine?
4. What is the most active agent for the clinical treatment of tuberculosis?
5. What is the function of dihydrofolate reductase in bacteria?
Was this article helpful?