Anti-leishmanial and immunomodulatory activities of extracts from Portulaca hirsutissima and Portulaca werdermannii

Costa, José Fernando Oliveira; Kiperstok, Alice Costa; David, Juceni P.; David, Jorge; Giulietti, Ana María; Queiroz, Luciano Paganucci de; Santos, Ricardo Ribeiro dos; Soares, Milena Botelho Pereira

doi:10.1016/j.fitote.2007.05.005

Cited by 16 publications

(11 citation statements)

References 8 publications

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“…[13] The murine macrophage J774.1 cell line (American Type Culture Collection, Manassas, VA) was cultured as well as described above, in fully supplemented RPMI, and incubated at 37°C in 5% CO 2 . [15] For evaluating the inhibitory activity of compounds against intracellular amastigotes, J774.1 macrophages were seeded into 96-well flat bottom plates at a density of 2 × 10 5 cells/ml and a total volume of 200 μl and were left to adhere overnight at 37°C in 5% CO 2 . [14] More specifically, 2.5 × 10 6 parasites/ml and 2 × 10 5 macrophages/ml were seeded into 96-well plates (in total volume 200 μl) and they were incubated for 72 hr with different concentrations of the compounds at 26 and 37°C (in 5% CO 2 ) respectively.…”

Section: Leishmanicidal Assays and Cytotoxicity Assays On Murine Mamentioning

confidence: 99%

Lipophilic conformationally constrained spiro carbocyclic 2,6‐diketopiperazine‐1‐acetohydroxamic acid analogues as trypanocidal and leishmanicidal agents: An extended SAR study

et al. 2017

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We have previously described a number of lipophilic conformationally constrained spiro carbocyclic 2,6-diketopiperazine (2,6-DKP)-1-acetohydroxamic acids as potent antitrypanosomal agents. In this report, we extend the SAR analysis in this class of compounds with respect to in vitro growth inhibition of Trypanosoma and Leishmania parasites. Introduction of bulky hydrophobic substituents at the vicinal position of the basic nitrogen atom in the spiro carbocyclic 2,6-DKP ring system can provide analogues which are potently active against bloodstream form Trypanosoma brucei and exhibit significant activities toward Trypanosoma cruzi epimastogotes and Leishmania infantum promastigotes and intracellular amastigotes. In particular, compounds possessing a benzyl or 4-chlorobenzyl substituent were found to be the most active growth inhibitors, with activities in the low nanomolar and low micromolar ranges for T. brucei and L. infantum, respectively. The benzyl-substituted (S)-enantiomer was the most potent derivative against T. brucei (IC = 6.8 nm), T. cruzi (IC = 0.21 μm), and L. infantum promastigotes (IC = 2.67 μm) and intracellular amastigotes (IC = 2.60 μm). Moreover, the (R)-chiral benzyl-substituted derivative and its racemic counterpart displayed significant activities against L. donovani. Importantly, the active compounds show high selectivity in comparison with two mammalian cell lines.

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Section: Leishmanicidal Assays and Cytotoxicity Assays On Murine Mamentioning

confidence: 99%

Lipophilic conformationally constrained spiro carbocyclic 2,6‐diketopiperazine‐1‐acetohydroxamic acid analogues as trypanocidal and leishmanicidal agents: An extended SAR study

et al. 2017

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“…V79, L929, Ehrlich, 3T3 fibroblasts, HepG2, Vero, Caco-2 and murine splenocytes are examples of very common cells used in cytotoxicity determination assays [23][24][25][26][27]. Nowadays, the reduction in the number of animals in research is stimulated by international, and the substitution of freshly isolated cells by cell lines is an option [28].…”

Section: Cytotoxicitymentioning

confidence: 99%

Early Toxicity Screening and Selection of Lead Compounds for Parasitic Diseases

Nogueira¹,

Costa²,

de³

et al. 2009

CDT

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Despite many advances made in disease mechanisms knowledge and drug discovery and development processes, the election of promising lead compounds continues to be a challenge. Efficient techniques are required for lead selection of hit compounds selected through in vitro pharmacological studies, in order to generate precise low cost throughput data with minimal amount of compound to support the right decision making. In this context, the selection of lead compounds with physicochemical parameters that will benefit orally bioavailable drugs are crucial for patients compliance and cost effectiveness, as well as for successful pharmacology. A concept based in Lipinski's rules point out the importance of analyzing these informations in early stages. A hepatocyte screening system may provide data on many processes such as drug-drug interaction, metabolite formation, drug toxicity and ADME profile of a hit. Drug-induced liver injury is the most frequent reason for the withdrawal of an approved drug from the market and hepatocytes have a central role in the metabolism of xenobiotics. Cytotoxicity screening assays can also give some information about toxicity early drug discovery process. A set of goals in lead compound selection must be shared between all areas involved so the chances of success can be improved in translational research.

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“…Numerous papers claim the in vitro antileishmanial activity of plant extracts. Some of the more recently published genera of interest are: Portulaca spp from Brazil [72] and Aphelandra spp, Byrsonima spp, Clucia spp, Tridax spp and Pentalinon spp from Mexico [73,74]. Some studies concern the in vitro evaluations of purified compounds.…”

Section: Plant Products Against Leishmaniamentioning

confidence: 99%

Development of new antileishmanial drugs – current knowledge and future prospects

Pape

2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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Leishmaniasis is a protozoan vector borne disease prevalent throughout the world and present in at least 88 countries. The parasite is transmitted by infected phlebotomine sandfly bites. While conventional therapies i.e. pentavalent antimonials, amphotericin B and pentamidine continue to play a major role, it is evident that new drugs or strategies must circumvent the limitations, such as a long-term parenteral administration, toxicity, the high cost in endemic countries and the emergence of resistance, that prevail. One of the most promising drugs is miltefosine, a new oral, approved alkylphospholipid for visceral leishmaniasis with only slight adverse effects. Although we have now this recent and encouraging advance, there is still a need to develop safe, efficient and affordable new treatments for the different clinical forms that exist. This review summarises conventional therapy and the current efforts in the discovery of drugs to treat leishmaniasis with the emphasis on drug combinations to enhance efficiency and prevent the emergence of resistance, the investigation of natural products with the objective of offering new bioactive chemical structures and the development of novel antileishmanial targets.

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Anti-leishmanial and immunomodulatory activities of extracts from Portulaca hirsutissima and Portulaca werdermannii

Cited by 16 publications

References 8 publications

Lipophilic conformationally constrained spiro carbocyclic 2,6‐diketopiperazine‐1‐acetohydroxamic acid analogues as trypanocidal and leishmanicidal agents: An extended SAR study

Lipophilic conformationally constrained spiro carbocyclic 2,6‐diketopiperazine‐1‐acetohydroxamic acid analogues as trypanocidal and leishmanicidal agents: An extended SAR study

Early Toxicity Screening and Selection of Lead Compounds for Parasitic Diseases

Development of new antileishmanial drugs – current knowledge and future prospects

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