Novel molecular targets and natural drug candidates for the antifungal therapy of seborrheic dermatitis.

Background: The prevalence of seborrheic dermatitis (SD) involving scalp and non-scalp areas has spread worldwide because of the decreasing susceptibility to azole antifungal drugs and increasing diffusion of the multidrug-resistant fungi of Malassezia species. The antifungal resistance results from structural changes of well-known and new molecular targets and biochemical adaptations of fungi to the standard synthetical treatment. Meanwhile, the research and use of traditional plant products as an alternative therapy strategy for dermatological diseases has increased tremendously over the past last decade. This review is the first to systematically summarize the latest in silico and in vitro data of Malassezia molecular targets, natural products and the innovative insights for the development of new drugs against SD. After a meticulous screening of 6255 scientific literature records and 104 relevant studies on the selected topic, the sixth novel molecular targets have been found: carbonic anhydrase, lipases, sphingomyelinases, phospholipases and ABC-transporters in Malassezia strains and aryl hydrocarbon receptors (AhR) in host skin cells mediated various biological responses to Malassezia indole ligands. The eighteen plant extracts, essential oils and their constituents have been identified as potential candidates affecting these targets. Despite the promising potential of the described molecular targets and the natural drug candidates, there is a lack of clinical effectiveness, safety and pharmacokinetic data at that moment. Further longitudinal studies are necessary to elucidate the mechanisms involved in Malassezia resistance and determine whether natural products alone and in combination with clinically recommended drugs could contribute to SD prophylaxis and effective treatment.