scholarly journals In vitro interaction between paromomycin sulphate and four drugs with leishmanicidal activity against three New World Leishmania species

2013 ◽  
Vol 69 (1) ◽  
pp. 150-154 ◽  
Author(s):  
E. de Morais-Teixeira ◽  
M. K. Gallupo ◽  
L. F. Rodrigues ◽  
A. J. Romanha ◽  
A. Rabello
Keyword(s):  
New World ◽  
Leishmania Species ◽  
Leishmanicidal Activity ◽  
In Vitro Interaction

scholarly journals The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant Leishmania species of Brazil

2011 ◽  
Vol 106 (4) ◽  
pp. 475-478 ◽  
Author(s):  
Eliane de Morais-Teixeira ◽  
Quesia Souza Damasceno ◽  
Mariana Kolos Galuppo ◽  
Alvaro José Romanha ◽  
Ana Rabello
Keyword(s):  
Leishmania Species ◽  
Leishmanicidal Activity

In vitro activity and in vivo efficacy of fexinidazole against New World Leishmania species

2019 ◽  
Vol 74 (8) ◽  
pp. 2318-2325 ◽  
Author(s):  
Eliane de Morais-Teixeira ◽  
Ana Rabello ◽  
Marta Marques Gontijo Aguiar
Keyword(s):  
Cutaneous Leishmaniasis ◽  
New World ◽  
Leishmania Species ◽  
Vitro Activity ◽  
In Vitro Assays ◽  
In Vitro Activity ◽  
In Vivo Evaluation ◽  
In Vivo Efficacy

Abstract Objectives To evaluate the in vitro activity and in vivo efficacy of fexinidazole against the main species that cause visceral and cutaneous New World leishmaniasis. Methods The inhibitory concentrations of fexinidazole against Leishmania (Leishmania) infantum chagasi, Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis in amastigotes were determined by in vitro activity assays. For the in vivo evaluation, animals were infected with L. (L.) infantum chagasi, L. (L.) amazonensis, L. (V.) braziliensis or Leishmania (Viannia) guyanensis and divided into groups: (i) control; and (ii) treated with oral fexinidazole, from 50 to 300 mg/kg/day. For cutaneous leishmaniasis, the size of the lesion was determined weekly after the beginning of the treatment. Upon completion, parasites were recovered from the spleen and liver, or skin lesion and spleen, and evaluated by a limiting dilution assay. Results All Leishmania isolates were susceptible to fexinidazole in the in vitro assays. The viable parasites in the liver and spleen were reduced with 100 and 300 mg/kg/day, respectively, for L. (L.) infantum chagasi. For the species causing cutaneous leishmaniasis, the viable parasites in lesions and the size of the lesions were reduced, starting from 200 mg/kg/day. The viable parasites in the spleen were also reduced with 200 and 300 mg/kg/day for L. (V.) braziliensis and L. (L.) amazonensis. Conclusions Considering the defined parameters, fexinidazole showed in vitro and in vivo activity against all tested species. This drug may represent an alternative treatment for the New World species.

Activity of Fenticonazole, Tioconazole and Nystatin on New World Leishmania Species

2019 ◽  
Vol 18 (27) ◽  
pp. 2338-2346 ◽  
Author(s):  
Eduardo Seiji Yamamoto ◽  
Jéssica Adriana Jesus ◽  
Adriana Bezerra-Souza ◽  
Márcia Dalastra Laurenti ◽  
Susan Pereira Ribeiro ◽  
...  
Keyword(s):  
New World ◽  
Parasite Species ◽  
Cutaneous Lesion ◽  
Leishmania Species ◽  
Health Condition ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Leishmanicidal Activity ◽  
Line Drug

Leishmaniasis is an infectious disease caused by protozoal parasites belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and health condition of patients. It can range from single cutaneous lesion until deadly visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and in some cases, the second-line drug, amphotericin B is used. Beside the toxicity of both drugs, parasites can be resistant to antimonial in some areas of the world. This makes fundamental the characterization of new drugs with leishmanicidal effect. Thus, the aim of the present work was to study the leishmanicidal activity of drugs able to interfere with ergosterol pathway (fenticonazole, tioconazole, nystatin, rosuvastatin and voriconazole) against promastigote and amastigote forms of L.(L.) amazonensis, L.(V.) braziliensis and L.(L.) infantum, and its impact on morphological and physiological changes in L.(L.) amazonensis or in host macrophages. We observed that fenticonazole, tioconazole and nystatin drugs eliminated promastigote and intracellular amastigotes, being fenticonazole and nystatin the most selective towards amastigote forms. Rosuvastatin and voriconazole did not present activity against amastigote forms of Leishmania sp. In addition, the drugs with leishmanicidal activity interfered with parasite mitochondrion. Although drugs did not stimulate NO and H2O2, specially fenticonazole was able to alkalize infected host macrophages. These results suggest well established and non-toxic antifungal drugs can be repurposed and used in leishmaniasis.

In vitro phototoxicity of ultradeformable liposomes containing chloroaluminum phthalocyanine against New World Leishmania species

2012 ◽  
Vol 117 ◽  
pp. 157-163 ◽  
Author(s):  
Indira Paola Hernández ◽  
Jorge Montanari ◽  
Wilfredo Valdivieso ◽  
Maria Jose Morilla ◽  
Eder Lilia Romero ◽  
...  
Keyword(s):  
New World ◽  
Leishmania Species ◽  
Chloroaluminum Phthalocyanine

Collagen fibrillogenesis in vitro: interaction of types I and V collagen

1986 ◽  
Vol 44 ◽  
pp. 210-211
Author(s):  
Arthur J. Wasserman ◽  
Kathy C. Kloos ◽  
David E. Birk
Keyword(s):  
Type I Collagen ◽  
Corneal Stroma ◽  
Minor Component ◽  
Homogeneous Distribution ◽  
Type I ◽  
Type V Collagen ◽  
Fibril Morphology ◽  
Type V ◽  
In Vitro Interaction

Type I collagen is the predominant collagen in the cornea with type V collagen being a quantitatively minor component. However, the content of type V collagen (10-20%) in the cornea is high when compared to other tissues containing predominantly type I collagen. The corneal stroma has a homogeneous distribution of these two collagens, however, immunochemical localization of type V collagen requires the disruption of type I collagen structure. This indicates that these collagens may be arranged as heterpolymeric fibrils. This arrangement may be responsible for the control of fibril diameter necessary for corneal transparency. The purpose of this work is to study the in vitro assembly of collagen type V and to determine whether the interactions of these collagens influence fibril morphology.

Naphthoquinones and derivatives for chemotherapy: perspectives and limitations of their anti-trypanosomatids activities

2020 ◽  
Vol 26 ◽  
Author(s):  
Luíza Dantas-Pereira ◽  
Edézio F. Cunha-Junior ◽  
Valter V. Andrade-Neto ◽  
John F. Bower ◽  
Guilherme A. M. Jardim ◽  
...  
Keyword(s):  
Large Scale ◽  
Neglected Tropical Diseases ◽  
Folk Medicine ◽  
Leishmania Species ◽  
Parasitic Infections ◽  
Mechanistic Analysis ◽  
Leishmania Spp ◽  
Nanomolar Range

: Chagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited and a search for alternatives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among all the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF3 on a phenyl amine ring inhibited T. brucei proliferation in the nanomolar range, and naphthopterocarpanquinones stood out for their activity on a range of Leishmania species. Some of these compounds showed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. Indeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo are essential for the development of a novel, specific and safe derivative, minimizing adverse effects.

In vitro interaction of ACTH with rat brain muscarinic receptors

Peptides ◽  
1986 ◽  
Vol 7 (3) ◽  
pp. 425-429 ◽  
Author(s):  
Jeroen A.D.M. Tonnaer ◽  
Marianna Van Vugt ◽  
Joop S. De Graaf
Keyword(s):  
Rat Brain ◽  
Muscarinic Receptors ◽  
In Vitro Interaction

scholarly journals Choriocarcinoma cells increase the number of differentiating human cytotrophoblasts through an in vitro interaction

1991 ◽  
Vol 266 (13) ◽  
pp. 8517-8522
Author(s):  
A. Hochberg ◽  
C. Sibley ◽  
M. Pixley ◽  
Y. Sadovsky ◽  
B. Strauss ◽  
...  
Keyword(s):  
Choriocarcinoma Cells ◽  
In Vitro Interaction

scholarly journals Identification of Potential Kinase Inhibitors within the PI3K/AKT Pathway of Leishmania Species

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1037
Author(s):  
Rodrigo Ochoa ◽  
Amaya Ortega-Pajares ◽  
Florencia A. Castello ◽  
Federico Serral ◽  
Darío Fernández Do Porto ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Screening Method ◽  
Molecular Targets ◽  
Leishmania Species ◽  
Akt Pathway ◽  
Protein Protein Interaction ◽  
Starting Point ◽  
Binding Pockets ◽  
Protein Protein Interaction Networks

Leishmaniasis is a public health disease that requires the development of more effective treatments and the identification of novel molecular targets. Since blocking the PI3K/AKT pathway has been successfully studied as an effective anticancer strategy for decades, we examined whether the same approach would also be feasible in Leishmania due to their high amount and diverse set of annotated proteins. Here, we used a best reciprocal hits protocol to identify potential protein kinase homologues in an annotated human PI3K/AKT pathway. We calculated their ligandibility based on available bioactivity data of the reported homologues and modelled their 3D structures to estimate the druggability of their binding pockets. The models were used to run a virtual screening method with molecular docking. We found and studied five protein kinases in five different Leishmania species, which are AKT, CDK, AMPK, mTOR and GSK3 homologues from the studied pathways. The compounds found for different enzymes and species were analysed and suggested as starting point scaffolds for the design of inhibitors. We studied the kinases’ participation in protein–protein interaction networks, and the potential deleterious effects, if inhibited, were supported with the literature. In the case of Leishmania GSK3, an inhibitor of its human counterpart, prioritized by our method, was validated in vitro to test its anti-Leishmania activity and indirectly infer the presence of the enzyme in the parasite. The analysis contributes to improving the knowledge about the presence of similar signalling pathways in Leishmania, as well as the discovery of compounds acting against any of these kinases as potential molecular targets in the parasite.

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