Current Topics in Medicinal Chemistry - Volume 18, Issue 15, 2018

Leishmaniasis is a neglected disease caused by protozoan belonging to the Leishmania genus. There are at least 16 pathogenic species for humans that are able to cause different clinical forms, such as cutaneous or visceral leishmaniasis. In spite of the different species and clinical forms, the treatment is performed with few drug options that, in most cases, are considered outdated. In addition, patients under classical treatment show serious side effects during drug administration, moreover parasites are able to become resistant to medicines. Thus, it is believed and well accepted that is urgent and necessary to develop new therapeutic options to overpass these concerns about conventional therapy of leishmaniasis. The present review will focus on the efficacy, side effects and action mechanism of classic drugs used in the treatment of leishmaniasis, as well as the importance of traditional knowledge for directing a rational search toward the discovery and characterization of new and effective molecules (in vivo assays) from plants to be used against leishmaniasis.

Giardia intestinalis infection causes enterocytes damage and loss of brush border of the epithelial cells of the intestine that leads to shortening of microvilli and altered epithelial barrier function. This pathology results in aqueous diarrhoea, steatorrhea, nausea, abdominal pain, vomiting and weight loss. However, most infections are asymptomatic. The main consequence of Giardia colonization is nutrients malabsorption. Several families of drugs with good efficacy are used for Giardia treatment, but sometime dosing regimens are suboptimal and emerging resistance begins to question their clinical value. Moreover, some of these drugs can cause side effects that result in patient discomfort and low adherence to the treatment. This paper reviews the drugs currently used for the treatment against Giardia: the mechanism of action, the efficacy, the normal dosing, side effects and in vitro and clinical studies. In addition, new therapies against Giardia such as those based on phytochemicals, Lactobacillus and nanotechnology are collected in this paper, trying to find the ideal treatment for this disease with maximum efficacy and minimum adverse effects.

Toxoplasmosis and neosporosis are closely related protozoan diseases that lead to important economic impacts in farm ruminants. Toxoplasma gondii infection mainly causes reproductive failure in small ruminants and is a widespread zoonosis, whereas Neospora caninum infection is one of the most important causes of abortion in cattle worldwide. Vaccination has been considered the most economic measure for controlling these diseases. However, despite vaccine development efforts, only a liveattenuated T. gondii vaccine has been licensed for veterinary use, and no promising vaccines against neosporosis have been developed; therefore, vaccine development remains a key goal. Additionally, drug therapy could be a valuable strategy for disease control in farm ruminants, as several drugs that limit T. gondii and N. caninum proliferation and dissemination have been evaluated. This approach may also be relevant to performing an initial drug screening for potential human therapy for zoonotic parasites. Treatments can be applied against infections in adult ruminants to minimize the outcomes of a primo-infection or the reactivation of a chronic infection during gestation or in newborn ruminants to avoid infection chronification. In this review, the current status of drug development against toxoplasmosis and neosporosis in farm ruminants is presented, and in an effort to promote additional treatment options, prospective drugs that have shown efficacy in vitro and in laboratory animal models of toxoplasmosis and neosporosis are examined.

Background: Candida albicans is an opportunistic yeast that causes more than 90% of all vulvovaginal infections. Because of being inherently resistant to antifungals drugs such as azole derivatives, the search for anti-Candida albicans agents with new pharmacological targets is considered as the main therapeutic strategy to prevent and treat these types of infections. In this context, products of natural origin are a promising source of compounds with antifungal activity. Objective: The current review analyzes clinical evidence on the effectiveness of natural products in the vulvovaginal Candida albicans infections. Method: A literature review in the electronic databases PubMed, Google Scholar, Cochrane Library Plus, Web of Science, Latin American and Caribbean Literature on Health Sciences (Lilacs) and Scientific Electronic Library Online (SciELO) using the search terms “Natural Products”, “Phytotherapy”, “Vulvovaginal Candidiasis” and “Clinical Trials” together with the Boolean term ‘AND’ was performed. English, Spanish and French articles without restriction of date of publication were considered. Results: A total of 13 clinical trials (most of them randomized clinical trials which used azoles as control group) evaluated the anti-Candida activity of a total of 11 different natural products (i.e. Zataria multiflora essential oils, Ageratina pichinchensis and Solanum nigrescens extracts and saponins from Solanum chrysotrichum, among others) against vulvovaginitis have been included in the current review. Conclusion: Because of the few clinical trials it is difficult to establish a consistent conclusion about the effectiveness of natural products in the prevention and treatment of vulvovaginitis caused by Candida albicans. Future studies should be aimed at evaluating new natural products as well as conducting more clinical research with promising natural substances already investigated in clinical trials.

The thermally-dimorphic systemic fungal group includes several important human pathogens: Blastomyces dermatitides, Coccidioides immitis and C. posadasii, Histoplasma capsulatum, Paracoccidioides brasiliensis, P. lutzii, and Talaromyces (Penicillium) marneffei. They usually are geographically restricted and have natural habitats in soil or in plants, and when fungal propagules invade mammalian host by inhalation, they initiate an inflammatory reaction that can result in self-resolution of the infection or cause an acute or chronic disease. In the setting of the AIDS pandemic and the developments in modern medicine, such as immunosuppressive therapy in cancer surgery patients and in transplantation and autoimmune diseases, the incidence of endemic mycoses has progressively increased. Another important factor of the increased incidence of systemic mycoses in certain regions is the progressive devastation of tropical and subtropical forests. In this review, we focus on two of the most important systemic mycoses: paracoccidioidomycosis and histoplasmosis, and their major characteristics in epidemiology, clinical aspects and laboratorial diagnosis.