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26-04-2012 | General practice | Article

Antidandruff drug target discovered


Free abstract

MedWire News: The enzyme MG-CA may be a potential drug target for a common form of dandruff, report researchers.

Claudiu Supuran (University of Firenze, Italy) and colleagues explain that the scalp-specific fungus Malassezia globosa is responsible for a large percentage of dandruff formation, although M. furfur and M. restricta have also been implicated. Other causes include excess sebum production and hereditary factors.

Two commonly used ingredients in antidandruff shampoos - zinc pyridinethione and ketoconazole - target fungus growth, with ketoconazole showing greater efficacy overall. However, neither is particularly effective at targeting M. globosa or related subspecies (spp.), particularly when the fungus is present at low levels.

Supuran and team therefore cloned and studied the M. globosa β-carbonic anhydrase MG-CA to assess its potential as a possible drug target.

They found that the activity of MG-CA was significantly inhibited by in vitro exposure to sulfonamides, a group of pre-existing antimicrobial agents, in the nanomolar to micromolar range.

In a mouse model of dandruff induced by Malassezia spp., the team found that 67% of mice treated with 4-(2-aminoethyl)benzenesulfonamide 5% solution demonstrated significant clinical improvement. But the experimental compound was not as effective as ketoconazole, as all the mice treated with this antifungal had significant clinical improvement.

Further investigation showed that exposure to 4-(2-aminoethyl)benzenesulfonamide resulted in fragmentation of fungal hyphae indicating the compound's potential for inhibition of fungal growth.

Using a wide variety of sulfonamide-related compounds, the researchers tested the minimum inhibitory concentration (MIC) required to inhibit β-carbonic anhydrases of several Malassezia spp.

The lowest MIC observed was 10 µg/mL with inhibitory activity against all of the Malassezia spp. tested. A few compounds had high MIC values (640 µg/mL), but the team says that "this may be a reflection of low cell permeability, a frequent problem with cell based assays."

These findings, which are published in the Journal of Medicinal Chemistry, add to those from previous research that have targeted carbonic anhydrases to fight infectious diseases.

For example, carbonic anhydrases from Plasmodium falciparum, Helicobacter pylori, Candida albicans, Cryptococcus neoformans, and Mycobacterium tuberculosis have all been suggested as potential drug targets.

Supuran and co-authors suggest that MG-CA holds promise as a new antidandruff drug target, although they emphasize that further research is needed.

By Helen Albert

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