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Tolnaftate: Chemical Structure, Mechanism of Action, SAR, Synthesis, Uses & Side effect

Chemical formula:

  • C19H17NOS

Structure of Tolnaftate
Structure of Tolnaftate

Mechanism of action:

  • Tolnaftate is a thiocarbamate antifungal that inhibits fungal squalene epoxidase, disrupting ergosterol synthesis and leading to the accumulation of toxic squalene, resulting in fungal cell death.

Structure-Activity Relationship (SAR) of Tolnaftate:

1.Thiocarbamate Group:

  • The thiocarbamate moiety in tolnaftate is crucial for its antifungal activity. This group is responsible for the inhibition of squalene epoxidase, an enzyme important in the biosynthesis of ergosterol, a key component of fungal cell membranes.

2.N-Methyl Group:

  • The presence of a methyl group on the nitrogen atom of the thiocarbamate is essential for biological activity. Alterations in this group can significantly impact the compound's antifungal efficacy.

3.Phenyl Ring:

  • The phenyl ring in tolnaftate contributes to the lipophilicity of the molecule, which is important for its ability to penetrate the fungal cell membrane.

4.Substituents on the Phenyl Ring:

  • The specific substituents on the phenyl ring, such as the chlorine atoms, play a role in defining the drug's potency and spectrum of activity against different fungal species.

Structure-Activity Relationship
Structure-Activity Relationship

Synthesis:

1.Formation of the Thiocarbamate Group:

  • This step involves creating the thiocarbamate moiety, which is central to Tolnaftate's antifungal activity. A typical reaction might be the reaction of an amine with a thiocarbamoyl chloride. For example:

  • Amine + Thiocarbamoyl Chloride → Thiocarbamate

2.Introduction of the N-Methyl Group:

  • Next, the N-methyl group is introduced. This is usually achieved by a methylation reaction using a methylating agent like methyl iodide:

  • Thiocarbamate + Methyl Iodide → N-Methylthiocarbamate

3.Attachment of the Phenyl Ring:

  • The phenyl ring is then attached to the thiocarbamate group. This step might involve a nucleophilic substitution reaction or a coupling reaction, depending on the starting materials:

  • N-Methylthiocarbamate + Phenyl Ring Precursor → Tolnaftate

Uses:

  • Tolnaftate is used to treat various superficial fungal infections, such as athlete's foot, ringworm, and jock itch.

Side effects:

  • Side effects are typically mild and may include local irritation, itching, or burning at the site of application.





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