New Drugs for Neglected Diseases in Latin America

In the last years an increasing demand for Grid Infrastructures has resulted in several international collaborations. This is the case of the EELA Project, which has brought together collaborating groups of Latin America and Europe. One year ago, the authors presented this e-infrastructure used, among others, by the biomedical groups for the studies of oncological analysis, neglected diseases, sequence alignments and computational phylogenetics. After this period, the achieved advances and the scientific results are summarized in this chapter

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Neglected diseases see few new drugs despite upped investment

Nature Medicine ◽

10.1038/nm0113-2 ◽

2013 ◽

Vol 19 (1) ◽

pp. 2-2 ◽

Cited By ~ 1

Author(s):

Cassandra Willyard

Keyword(s):

New Drugs ◽

Neglected Diseases

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New Drugs for Neglected Diseases: From Pipeline to Patients

PLoS Medicine ◽

10.1371/journal.pmed.0010006 ◽

2004 ◽

Vol 1 (1) ◽

pp. e6 ◽

Cited By ~ 41

Author(s):

Bernard Pécoul

Keyword(s):

New Drugs ◽

Neglected Diseases

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Antileishmanial and Immunomodulatory Effect of Babassu-Loaded PLGA Microparticles: A Useful Drug Target to Leishmania amazonensis Infection

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/3161045 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 5

Author(s):

Mayara Cristina Pinto da Silva ◽

Jefferson Mesquita Brito ◽

Amalia dos Santos Ferreira ◽

Andre Alvares Marques Vale ◽

Ana Paula Azevedo dos Santos ◽

...

Keyword(s):

Ex Vivo ◽

Macrophage Polarization ◽

Leishmania Amazonensis ◽

Immunomodulatory Effect ◽

New Drugs ◽

Neglected Diseases ◽

High Morbidity ◽

Intracellular Parasites ◽

Plga Microparticles ◽

Great Relevance

The immunological and the anti-Leishmania amazonensis activity of babassu-loaded poly(lactic-co-glycolic acid) [PLGA] microparticles was evaluated. The anti-Leishmania activity was evaluated against promastigotes or amastigotes forms, in Balb/c macrophages. The size of the microparticles ranged from 3 to 6.4 μm, with a zeta potential of −25 mV and encapsulation efficiency of 48%. The anti-Leishmania activity of the PLGA microparticles loaded with the aqueous extract of babassu mesocarp (MMP) (IC50) was 10-fold higher than that free extract (Meso). MMP exhibited overall bioavailability and was very effective in eliminating intracellular parasites. MMP also reduced ex vivo parasite infectivity probably by the increased production of nitric oxide, hydrogen peroxide, and TNF-α indicating the activation of M1 macrophages. The overexpression of TNF-α did not impair cell viability, suggesting antiapoptotic effects of MMP. In conclusion, babassu-loaded microparticles could be useful for drug targeting in the treatment of leishmaniasis, due to the immunomodulatory effect on macrophage polarization and the increased efficacy as an anti-Leishmania product after the microencapsulation. These findings are of great relevance since the development of new drugs for the treatment of neglected diseases is desirable, mainly if we consider the high morbidity and mortality rates of leishmaniasis worldwide.

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Capsaicin inhibits arginine kinase and exerts anti-Trypanosoma cruzi activity

10.1101/2020.06.23.167346 ◽

2020 ◽

Author(s):

Edward A. Valera-Vera ◽

Chantal Reigada ◽

Melisa Sayé ◽

Fabio A. Digirolamo ◽

Mariana R. Miranda ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Stress Responses ◽

Mammalian Cells ◽

Arginine Kinase ◽

Chronic Phase ◽

New Drugs ◽

World Health ◽

Neglected Diseases ◽

Health Organization

ABSTRACTTrypanosoma cruzi is the causative agent of Chagas disease, considered within the list of twenty neglected diseases according to the World Health Organization. There are only two therapeutic drugs for Chagas disease, both of them unsuitable for the chronic phase, therefore the development of new drugs is a priority.T. cruzi arginine kinase (TcAK) is a promising drug target since it is absent in humans and it is involved in cellular stress responses. In a previous study from our laboratory, possible TcAK inhibitors were identified through computer simulations, resulting in the best-scoring compounds cyanidin derivatives and capsaicin. Considering these results, in this work we evaluate the effect of capsaicin on TcAK activity and its trypanocidal effect. Although capsaicin produced a weak inhibition on the recombinant TcAK activity (IC50 ≈ 800 µM), it had a strong trypanocidal effect on epimastigotes and trypomastigotes (IC50 = 6.26 µM and 0.26 µM, respectively) being 20-fold more active on trypomastigotes than mammalian cells. Epimastigotes that overexpress TcAK were 37% more resistant to capsaicin than wild type parasites, suggesting that trypanocidal activity could be due, in part, to the enzyme inhibition. However, the difference between the concentrations at which the enzyme is inhibited and the parasite death is caused implies the presence of other targets. In this sense, the prohibitin-2 and calmodulin were identified as other possible capsaicin targets. Capsaicin is a strong and selective trypanocidal agent active in nanomolar concentrations, with an IC50 57-fold lower than benznidazole, the drug currently used for treating Chagas disease.

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Funding of clinical trials in Brazil for the development of new drugs: who are the sponsors?

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20151236 ◽

2015 ◽

Vol 2 (4) ◽

pp. 75 ◽

Cited By ~ 1

Author(s):

Ricardo Eccard da Silva ◽

Angélica Amorim Amato ◽

Maria Rita Carvalho Garbi Novaes

Keyword(s):

Clinical Trials ◽

Pharmaceutical Industry ◽

The Other ◽

New Drugs ◽

Essential Medicines ◽

Neglected Diseases ◽

Active Pharmaceutical Ingredients ◽

Pharmaceutical Ingredients ◽

Funding Sources ◽

Other Hand

Background: A low rate of investment in science it is directly impacts the technological independence and capacity in health care costs. Knowledge of funding sources is critical to understand the problem and formulates hypotheses for future studies.Methods: Two databases were used: the System for Control of Clinical Research (SCCR) from the Brazilian Health Surveillance Agency (Anvisa), and the International Clinical Trials Registry Platform (ICTRP). Results: From 2009 to 2012, 77% of the clinical trials approved by Anvisa were sponsored by transnational pharmaceutical industry. On the other hand, the national pharmaceutical industry sponsored 8% of the trials over the same period. The most frequent sponsor of clinical trials involving drugs registered in the ICTRP from 2011 to 2012 was the transnational pharmaceutical industry (43%). Among the trials with national sponsors, are those involving neglected diseases such as chronic hepatitis C (ICD X B18.2), cutaneous leishmaniasis (ICD X B55.1) and yellow fever (ICD X A95), which were all sponsored by national governmental foundations. None of the active pharmaceutical ingredients studied by the transnational pharmaceutical industry or the transnational biopharmaceutical company were in the national list of essential medicines. On the other hand, 83% and 66.6% of the active pharmaceutical ingredients studied by national private universities and the international governmental agency, respectively, are in the national list of essential medicines. Conclusions: The national pharmaceutical industry and government still invests little in Research and Development (R&D) activities, when compared with transnational industries. This affects directly its technological and innovation ability.

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In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, an N-Acyl Hydrazone Derivative Phosphodiesterase-4 Inhibitor, Against Leishmania amazonensis

Frontiers in Pharmacology ◽

10.3389/fphar.2020.590544 ◽

2020 ◽

Vol 11 ◽

Author(s):

Dahara Keyse Carvalho Silva ◽

Jessicada Silva Teixeira ◽

Diogo Rodrigo Magalhães Moreira ◽

Tiago Fernandes da Silva ◽

Eliezer Jesus de Lacerda Barreiro ◽

...

Keyword(s):

Lesion Size ◽

Current Treatment ◽

New Drugs ◽

Ultrastructural Changes ◽

Neglected Diseases ◽

Mitochondrial Potential ◽

Worldwide Distribution ◽

Low Cytotoxicity

Leishmaniasis are group of neglected diseases with worldwide distribution that affect about 12 million people. The current treatment is limited and may cause severe adverse effects, and thus, the search for new drugs more effective and less toxic is relevant. We have previously investigated the immunomodulatory effects of LASSBio-1386, an N-acylhydrazone derivative. Here we investigated the in vitro and in vivo activity of LASSBio-1386 against L. amazonensis. LASSBio-1386 inhibited the proliferation of promastigotes of L. amazonensis (EC50 = 2.4 ± 0.48 µM), while presenting low cytotoxicity to macrophages (CC50 = 74.1 ± 2.9 µM). In vitro incubation with LASSBio-1386 reduced the percentage of Leishmania-infected macrophages and the number of intracellular parasites (EC50 = 9.42 ± 0.64 µM). Also, in vivo treatment of BALB/c mice infected with L. amazonensis resulted in a decrease of lesion size, parasitic load and caused histopathological alterations, when compared to vehicle-treated control. Moreover, LASSBio-1386 caused ultrastructural changes, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of L. amazonensis. Aiming to its possible molecular interactions, we performed docking and molecular dynamics studies on Leishmania phosphodiesterase B1 (PDB code: 2R8Q) and LASSBio-1386. The computational analyses suggest that LASSBio-1386 acts against Leishmania through the modulation of leishmanial PDE activity. In conclusion, our results indicate that LASSBio-1386 is a promising candidate for the development of new leishmaniasis treatment.

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First Example of Antiparasitic Activity Influenced by Thermochromism: Leishmanicidal Evaluation of 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine Metal Complexes

Medicinal Chemistry ◽

10.2174/1573406415666190401120607 ◽

2020 ◽

Vol 16 (3) ◽

pp. 422-430 ◽

Cited By ~ 1

Author(s):

José M. Méndez-Arriaga ◽

Itziar Oyarzabal ◽

Álvaro Martín-Montes ◽

Judith García-Rodríguez ◽

Miguel Quirós ◽

...

Keyword(s):

Physical Properties ◽

Metal Complexes ◽

New Drugs ◽

Host Cells ◽

World Health ◽

Neglected Diseases ◽

Leishmania Spp ◽

Different Strains ◽

Health Organization

Background: The World Health Organization catalogues illnesses such as Leishmaniasis as neglected diseases, due to low investment in new drugs to fight them. The search of novel and non-side effects anti-parasitic compounds is one of the urgent needs for the Third World. The use of triazolopyrimidines and their metallic complexes has demonstrated hopeful results in this field. Objective: This work studies the antiparasitic efficacy of a series of 5,7-dimethyl-1,2,4- triazolo[1,5-a]pyrimidine first row transition metal complexes against three leishmania spp. strains. Methods: The in vitro antiproliferation of promastigote forms of different strains of leishmania spp. (L. infantum, L. braziliensis and L donovani) and the cytotoxicity in macrophage host cells are reported here. The antiparasitic assays have been complemented with enzymatic tests to elucidate the mechanisms of action. New crystal structure description, thermal analysis, magnetic susceptibility and magnetization experiments have also been carried out in order to present a whole characterization of the studied compounds and interesting physical properties besides the biological tests. Results: The results of antiproliferation screening and cytotoxicity show great antiparasitic efficacy in the studied complexes. The superoxide dismutase enzymatic assays exhibit a different behaviour according to the thermochromic triazolopyrimidine form tested. Conclusion: Antiproliferative assays and enzymatic tests corroborate the synergetic leishmanicidal effect present in coordination triazolopyrimidine complexes. The changes in coordination sphere derived from thermochromism affect the physical properties as well as the biological efficacy.

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Características clínicas y para clínicas de los pacientes con fiebre manchada por Rickettsia rickettsii en Panamá (1950-1951; 2004-2018)

Revista Médica de Panamá - ISSN 2412-642X ◽

10.37980/im.journal.rmdp.2019794 ◽

2019 ◽

Vol 39 (3) ◽

Author(s):

Carlos Daza ◽

Sergio Eduardo Bermúdez Castillero

Keyword(s):

Latin America ◽

Mortality Rate ◽

Clinical Characteristics ◽

Spotted Fever ◽

Clinical Suspicion ◽

Neglected Diseases ◽

Rickettsia Rickettsii ◽

Tick Borne Disease ◽

America Latina ◽

Low Prevalence

[Clinical and para clinical characteristics of patients with fever spotted by Rickettsia  rickettsii in Panama (1950-1951; 2004-2017)] Resumen La fiebre manchada causada por Rickettsia rickettsii es por mucho la enfermedad transmitida por garrapatas más importante en América Latina y una de las zoonosis más relevante del continente. En Panamá esto es notorio si se considera que los casos confirmados de la misma se han registrado en dos series: 1950-1951, donde se presentaron cinco casos, donde los dos primeros fueron resultaron fatales, y de 2004-2017, donde se confirmaron 10 casos, con nueve fallecimientos. A pesar de lo anterior, la fiebre manchada causada por R. rickettsii es una enfermedad de baja prevalencia y está dentro de las enfermedades desatendidas. El diagnóstico oportuno de R. rickettsii en personas afectadas por la misma, incrementa la posibilidad de sobrevivencia del paciente; sin embargo, a pesar de su alto porcentaje de mortalidad, esta enfermedad es poco reconocida y no se cuenta con sospecha clínica. Con el objetivo de presentar sus características clínicas en Panamá, se analizan individualmente cada reportes de caso, incluyendo datos etarios, de localidad, síntomas descritos, análisis aplicados y tratamiento. Abstract The spotted fever caused by Rickettsia rickettsii is by far the most important tick-borne disease in Latin America and one of the most important zoonoses in the continent. In Panama this is notorious if it is considers that the confirmed cases have been registered in two series: 1950-1951, with five cases and two fatal; and 2004-2017, with 10 cases and nine deaths. Despite the above, spotted fever caused by R. rickettsii is a disease of low prevalence and is among the neglected diseases. The timely diagnosis of R. rickettsii in people affected by it, increases the possibility of survival of the patient; however, despite its high mortality rate, this disease is poorly recognized and there is no clinical suspicion. In order to present their clinical characteristics in Panama, each reports of case is analyzed individually, including age, location, symptoms described, applied analysis and treatment.

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