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Leishmanicide activity evaluation of new nitrophenols and n-aroylcianaceto-hydrazides against Leishmania species from the New World

Grant number: 18/22290-4
Support Opportunities:Research Grants - Innovative Research in Small Business - PIPE
Duration: July 01, 2019 - April 30, 2020
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Jan Carlo Morais Oliveira Bertassoni Delorenzi
Grantee:Jan Carlo Morais Oliveira Bertassoni Delorenzi
Host Company:Neguebe Química e Biológica Ltda
CNAE: Fabricação de produtos farmoquímicos
Pesquisa e desenvolvimento experimental em ciências físicas e naturais
Atividades profissionais, científicas e técnicas não especificadas anteriormente
City: São Paulo
Associated grant(s):20/01465-0 - Combining in silico and experimental techniques to develop next generation drug like molecules for neglected diseases - leishmaniasis, AP.PIPE


World Health Organization (WHO) defines Neglected Tropical Diseases (NTDs) as a heterogeneous group of communicable diseases prevalent in tropical and subtropical areas of 149 countries and affecting more than one billion people, bringing a high social and economic cost to developing countries. Tropical diseases such as malaria, Chagas' disease, sleep sickness and Leishmaniasis remain as some of the leading causes of morbidity and mortality worldwide. Leishmaniasis is a worldwide anthropozoonosis, being endemic in 98 countries distributed in Africa, Asia, Europe and America. It is estimated that 12 million people have already been infected with the disease, with clinical manifestations or not; between 0.9 and 1.6 million new cases occur each year. The strategies for preventive control this disease have been ineffective in view of the increase in the number of cases and the particular appearance of cases in large urban centers in Brazil and in several regions of southern Europe. The drugs that are on the market present a series of problems, such as resistance of the parasite and induction of adverse side effects, that limit their use and mainly its effectiveness. In addition, all drugs available in Brazil and most of the countries affected are of parenteral administration, which requires patient collaboration; unfortunately, many abandon treatment, a fact that favors the emergence of resistant strains. Developing innovative molecules with high leishmanicidal potential and low cytotoxicity, expanding the arsenal of drugs that can be used to treat leishmaniasis is the main goal of the project.Nitrated compounds will be obtained from carbonyl groups substituted phenols. Acetylation, prenylation and benzoylation reactions will be carried out from these nitrophenols to introduce the acetyl, prenyl and benzoyl groups, respectively, into the aromatic ring and thus to increase the bioactive potential of these nitroderivatives. Further novel 1-aroyl-2-(3-amino-2-bromo-1,3-dioxopropyl) hydrazides and the corresponding dibrominated compounds, N-aroylcyanacetaldehydes will react with phosphorus oxychloride and dimethylformamide to form chlorovinylaldehydes which will be converted by the Knoevenagel condensation reaction on push-pull butadienes. From the N-aroylcyanoacetahydrazides it is possible, by Knoevenagel condensation with the nitrobenzaldehydes, to isolate novel 1-aroyl-2- (2-cyano-1-oxo-3-phenyl-2-propen-1-yl)-hydrazides. The purity of the compounds will be evaluated by high performance liquid chromatography (HLPC). Once pure, they will be sent for spectroscopic characterization and organic elemental analysis. The methodologies to be used will evaluate not only the leishmanicidal potential of the drugs, but also their possible cytotoxicity and probable mechanism of action. (AU)

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