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Among neglected tropical diseases, leishmaniasis is one of the most relevant with an estimated 30,000 deaths annually. Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost; therefore, new safer and shorter treatments are needed for this disease. Here we report on the synthesis of novel 4-amino-7-chloroquinoline-based compounds with leishmanicidal activity, together with deeper insight into the mechanism of action of our previously published hit compound 1. New derivatives showed comparable activity to 1 against both promastigote and intracellular amastigote forms of Leishmania infantum, with IC < 1 μM. Furthermore, we have determined that compound 1 induced a decrease of intracellular ATP levels, as well as a mitochondrial depolarization, together with an alteration of plasma membrane permeability and a significant ROS production. The inhibition of the energy metabolism of Leishmania plays an important role in the leishmanicidal mechanism of this compound. In all, these results support the consideration of compound 1 for the future development of new leishmanicidal drugs.
This article was published in the following journal.
Name: European journal of medicinal chemistry
Traditional antimalarial drugs based on 4-aminoquinolines have exhibited good antiproliferative activities against Leishmania parasites; however, their clinical use is currently limited. To identify n...
Leishmania, one of the most important neglected tropical diseases, is endemic in several regions of the world and hence regarded as a serious threat to public health. Major difficulties with current c...
The treatment of human leishmaniasis is currently based on few compounds that are highly toxic, expensive and have a high rate of treatment failure. A number of recent studies on new drugs focuses on ...
We report new organoselenium compounds bearing the sulfonamide moiety as effective inhibitors of the β-isoform of Carbonic Anhydrase from the unicellular parasitic protozoan L. donovani chagasi. All ...
This communication describes a Cu-mediated ortho-C-H radiofluorination of aromatic carboxylic acids that are protected as 8-aminoquinoline benzamides. The method uses K¹⁸F and is compatible with a ...
The aim of the present study is to compare the effect of two weight loss interventions inducing the same energy deficit but one based on exercise and one using dietary restriction, on appe...
Therapeutic strategies for multiple sclerosis (MS) are essentially based on the use of immunomodulatory agents such as interferon b and glatirmere acetate, but their efficacy is quite limi...
This will be a phase IV, open label, multicenter, randomized pragmatic study in frail elderly patients with COPD. Participants will be treated with either inhaled LABD alone or LABD combin...
Among the many changes associated with the impact of HIV and the long-term use of antiretroviral therapy, metabolics are important because they are important risk factors for the developme...
The purpose of this research is to investigate how using different methods to reduce the energy density of entrees affects daily energy intake in adults. It is hypothesized that reducing t...
Compounds that inhibit or prevent the proliferation of CELLS.
Organic compounds composed of tin and three methyl groups. Affect mitochondrial metabolism and inhibit oxidative phosphorylation by acting directly on the energy conserving processes.
Organic compounds composed of tin and three ethyl groups. Affect mitochondrial metabolism and inhibit oxidative phosphorylation by acting directly on the energy conserving processes.
Strong alkylating and immunosuppressive agents whose biological activity is based on the presence of bis(2-chloroethyl)- groups. Although otherwise structurally diverse, the compounds have in common the capacity to contribute alkyl groups to DNA. They are generally highly toxic but include among their number many widely used and effective antineoplastic agents.
Compounds that inhibit H(+)-K(+)-EXCHANGING ATPASE. They are used as ANTI-ULCER AGENTS and sometimes in place of HISTAMINE H2 ANTAGONISTS for GASTROESOPHAGEAL REFLUX.
Tropical Medicine is the study of diseases more commonly found in tropical regions than elsewhere. Examples of these diseases are malaria, yellow fever, Chagas disease, Dengue, Helminths, African trypanosomiasis, Leishmaniasis, Leprosy, Lymphatic filaria...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...