2. Universidad Cardenal Herrera-CEU

Leishmaniasis, African sleeping sickness and Chagas disease, caused by the kinetoplastid parasites Leishmania spp, Trypanosoma brucei and Trypanosoma cruzi, respectively, are among the most important parasitic diseases, affecting millions of people and considered to be within the most relevant group of neglected tropical diseases. The main alternative to control such parasitosis is chemotherapy. Nevertheless, the current chemotherapeutic treatments are far from being satisfactory. This review outlines the current understanding of different drugs against leishmaniasis, African sleeping sickness and Chagas disease, their mechanism of action and resistance. Recent approaches in the area of anti-leishmanial and trypanocidal therapies are also enumerated, new modulators from the mode of action, development of new formulations of old drugs, therapeutic switching and “in silico” drug design.

A series of compounds containing the nitrobenzene and sulfonamido moieties were synthesized and their leishmanicidal effect was assessed in vitro against Leishmania infantum promastigotes. Among the compounds evaluated, the p-nitrobenzenesulfonamides 4Aa and 4Ba, and the p-nitroaniline 5 showed significant activity with a good selectivity index. In a Balb/c mice model of L. Infantum, administration of compounds 4Aa, 4Ba or 5 (5 mg/kg/day for 10 days, injected ip route) led to a clear-cut parasite burden reduction (ca. 99%). In an attempt to elucidate their mechanism of action, the DNA interaction of 4Aa and 5 was investigated by means of viscosity studies, thermal denaturation and nuclease activity assay. Both compounds showed nuclease activity in the presence of copper salt. The results suggest that compounds 4Aa, 4Ba and 5 represent possible candidates for drug development in the therapeutic control of leishmaniasis.

Percutaneous transdermal absorption of esculetin (6,7-dihydroxycoumarin), an oxidative damage inhibitor, was evaluated by means of in vitro permeation studies in which vertical Franz-type diffusion cells and pig ear skin were employed. To determine the absorption of esculetin, we validated a simple, accurate, precise, and rapid HPLC-UV method. Additionally, the effects of several percutaneous enhancers were studied. Pretreatment of porcine skin was performed with ethanol (control vehicle), decenoic acid, oleic acid, R-(+)-limonene, and laurocapram (Azone®) (5% in ethanol, w/w, respectively). Pretreatment of skin with oleic acid or laurocapram led to statistically significant differences in the transdermal flux of esculetin with respect to controls. Of the two enhancers, laurocapram showed the greatest capacity to enhance the flux of esculetin across pig skin.

Vitiligo is a chronic disease of unknown etiology that causes progressive cutaneous depigmentation. Current pharmacological treatments have limited success and present significant risks. Many efforts have been made in recent years to explore new anti-vitiligo therapeutic strategies, including herbal-based therapies. The objective of the present review is to provide an updated overview on the most frequently used medicinal plants in the treatment of vitiligo. A bibliographical search was carried out in scientific databases Pubmed, Scifinder, Scopus, Google Scholar, and Medline up to October 2021 using the descriptors vitiligo, herbal, medicinal plants, and alternative therapies. In our search, the highest number of published studies comprise plants commonly used in traditional herbal medicine, highlighting the usefulness of ethnopharmacology in the discovery of new therapeutic agents. The review outlines current understanding and provides an insight into the role of psoralens and khellin (photosensitizing agents obtained from plants such as Cullen corylifolium or Ammi visnaga). The paper also describes other traditional herbs such as Ginkgo biloba, Phlebodium aureum, Piper nigrum, Picrorhiza kurroa, and Baccharoides anthelmintica that can likewise act as potential therapeutical agents. Based on our findings, photosensitizing agents in combination with phototherapy, the association of oral Phebodium aureum with phototherapies as well as oral G. biloba in monotherapy showed greater scientific evidence as therapeutic options. The research results emphasize that further investigation in this area is merited. More long-term follow up clinical trials and higher quality randomized trials are needed.