Miscellaneous agents

Antifungal Agents - Synthesis and Drug Profile

Miscellaneous agents

1. Naftifine (Nabtin)

Synthesis

Mode of action: The drug has fungicidal activity against Tinea cruris and Corporis spp. This inhibits squalene 2,3-epoxidase and thus, inhibits fungal biosynthesis of ergosterol.

Dose: It is administered as 1% cream twice daily.

2. Ciclopirox

Synthesis

Properties and uses: Ciclopirox is a white or yellowish-white crystalline powder, slightly soluble in water, soluble in ethanol and in methylene chloride. It is available as 1% cream on cotton for the treatment of cutaneous candidiasis and for Tinea corporis, T. cruris, T. pedis, and Pityriasis versicolour.

Assay: Dissolve the sample in methanol, add water, and titrate with 0.1 M sodium hydroxide. Determine the end point potentiometrically.

3. Tolnaftate

Synthesis

Properties and uses: Tolnaftate is a white or yellowish-white powder practically insoluble in water, soluble in acetone and in methylene chloride, and very slightly soluble in alcohol. It is effective for the treatment of most cutaneous mycoses, such as Trichophyton rubrum and Microsporum canis. Replacement of the aromatic methyl group by hydroxy or methoxy or its removal does not affect potency. Replacement of the complete tolyl group by a α-napthyl or a β-napthyl substituent does not decrease its potency. It is nontoxic.

Dose: The administered dose is 1% as a cream, gel, powder, aerosol powder, and topical solution, applied locally twice a day.

Assay: Dissolve the sample in methanol, measure the absorbance, after its dilution with methanol, at the maxima at 257 nm, using ultraviolet spectrophotometer.

4. Terbinafine

Synthesis

Mode of action: The uses and mechanism of action of terbinafine are the same as those of naffine. It is active by virtue of its ability to block squalene epoxidase.

Metabolism: Several CYP450 enzymes, including CYP1A₂, CYP2C1₉, CYP2C₉, CYP2C₈, CYP3A₄, and CYP2B₆, extensively metabolize it.

Properties and uses: Terbinafine hydrochloride is a white powder, slightly soluble in water and in acetone, soluble in anhydrous ethanol and in methanol. It is used as an antifungal agent.

Assay: Dissolve the sample in ethanol, add 0.01 M hydrochloric acid, and titrate with 0.1 M sodium hydroxide. Determine the end point potentiometrically.