Novel ruthenium(iii) complexes with hydroxybenzophenones: experimental and theoretical characterization and in vitro leishmanicidal activity comparing complexes and ligands

ABSTRACTConventional chemotherapy against leishmaniasis includes agents exhibiting considerable toxicity. In addition, reports of drug resistance are not uncommon. Thus, safe and effective therapies are urgently needed. Isoselenocyanate compounds have recently been identified with potential antitumor activity. It is well known that some antitumor agents demonstrate effects againstLeishmania. In this study, thein vitroleishmanicidal activities of several organo-selenium and organo-sulfur compounds were tested againstLeishmania majorandLeishmania amazonensisparasites, using promastigotes and intracellular amastigote forms. The cytotoxicity of these agents was measured in murine peritoneal macrophages and their selectivity indexes were calculated. One of the tested compounds, the isoselenocyanate derivative NISC-6, showed selectivity indexes 2- and 10-fold higher than those of the reference drug amphotericin B when evaluated inL. amazonensisandL. major, respectively. The American strain (L. amazonensis) was less sensitive to NISC-6 thanL. major, showing a trend similar to that observed previously for amphotericin B. In addition, we also observed that NISC-6 significantly reduced the number of amastigotes per infected macrophage. On the other hand, we showed that NISC-6 decreases expression levels ofLeishmaniagenes involved in the cell cycle, such astopoisomerase-2(TOP-2),PCNA, andMCM4, therefore contributing to its leishmanicidal activity. The effect of this compound on cell cycle progression was confirmed by flow cytometry. We observed a significant increase of cells in the G1phase and a dramatic reduction of cells in the S phase compared to untreated cells. Altogether, our data suggest that the isoselenocyanate NISC-6 may be a promising candidate for new drug development against leishmaniasis.

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Leismanicidal Activity of Propolis Collected in the Semiarid Region of Brazil

Frontiers in Pharmacology ◽

10.3389/fphar.2021.702032 ◽

2021 ◽

Vol 12 ◽

Author(s):

Giani Maria Cavalcante ◽

Celso Amorim Camara ◽

Eva Monica Sarmento Da Silva ◽

Mariana Silva Santos ◽

Anderson Brandão Leite ◽

...

Keyword(s):

Cytotoxic Effect ◽

Ethanolic Extract ◽

Ultra Performance Liquid Chromatography ◽

Semiarid Region ◽

Array Detector ◽

Significant Activity ◽

Exact Mass ◽

Leishmanicidal Activity ◽

Etoh Extract

Objective: The aim of the current study is to investigate the chemical composition, cytotoxic effect, and leishmanicidal activity of propolis collected in the semi-arid region of Bahia, Brazil.Methods: EtOH extract, hexane, EtOAc and MeOH fractions from propolis were analyzed by ultra-performance liquid chromatography coupled with diode array detector and quadrupole time-of-flight mass spectrometry. The identification was based on the exact mass, general fragmentation behaviors and UV absorption of the flavonoids. The in vitro cytotoxic effect and leishmanicidal activity of ethanolic extract, hexane, ethyl acetate, and methanolic fractions of propolis were evaluated.Results: Five triterpenes and twenty-four flavonoids were identified. The propolis did not present toxicity to the host cell up to the maximum concentration tested. In addition, all tested samples showed statistically significant activity against promastigotes of Leishmania chagasi and Leishmania amazonensis. Regarding the activity against amastigote forms of L. amazonensis, the hexane fraction, presented statistically significant activity with IC50 of 1.3 ± 0.1 μg/ml.Conclusion: The results support the idea that propolis can be used for future antileishmania studies.

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In Vitro Leishmanicidal Activity of Benzophenanthridine Alkaloids from Bocconia pearcei and Related Compounds

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.58.1047 ◽

2010 ◽

Vol 58 (8) ◽

pp. 1047-1050 ◽

Cited By ~ 30

Author(s):

Hiroyuki Fuchino ◽

Marii Kawano ◽

Kanami Mori-Yasumoto ◽

Setsuko Sekita ◽

Motoyoshi Satake ◽

...

Keyword(s):

Benzophenanthridine Alkaloids ◽

Leishmanicidal Activity ◽

Related Compounds

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In vitro leishmanicidal activity of N-dodecyl-1,2-ethanediamine

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2011.10.005 ◽

2012 ◽

Vol 66 (3) ◽

pp. 180-186 ◽

Cited By ~ 8

Author(s):

Alexandre L. Neves Silva ◽

Camila M. Adade ◽

Fernanda M. Shoyama ◽

Cecílio Purcino S. Neto ◽

Thaís S. Padrón ◽

...

Keyword(s):

Leishmanicidal Activity

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Synthesis and Evaluation of Anti-Rhinovirus 1B Activity of Oxazolinyl-Isoflavans and -3(2H)-Isoflavenes

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029200300402 ◽

1992 ◽

Vol 3 (4) ◽

pp. 195-202 ◽

Cited By ~ 16

Author(s):

N. Desideri ◽

C. Conti ◽

I. Sestili ◽

P. Tomao ◽

M. L. Stein ◽

...

Keyword(s):

Carboxylic Acid ◽

Antiviral Activity ◽

Cytopathic Effect ◽

Potent Inhibitor ◽

Therapeutic Index ◽

Intermediate Compound ◽

Plaque Formation ◽

Interesting Compound ◽

Viral Cytopathic Effect

Oxazolinyl-isoflavans and −3(2H)-isoflavenes, substituted or not with a chlorine atom, were synthesized in order to compare their anti-rhinovirus activity with that of previously studied analogous compounds. The activity of the oxazolines and of the esters and acids, which are intermediates in the synthesis, was studied in vitro against rhinovirus serotype 1B infection in HeLa cells. The ability of various non cytotoxic concentrations to interfere with the development of the viral cytopathic effect and plaque formation was examined. All the tested compounds exerted a significant antiviral activity, and most of them were as active as some representative compounds of the oxazolinyl-phenoxyalkylisoxazole (WIN) series. 6-Oxazolinylisoflavan (VI) appeared to be the most interesting compound due to its high activity and therapeutic index. Among the substituted isoflavans and isoflavenes tested so far, the intermediate compound 6-chloro-3 (2H)-isoflavene-4′-carboxylic acid (XIX) was unexpectedly the most potent inhibitor of rhinovirus 1B plaque formation.

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Ultrastructural Changes and Death ofLeishmania infantumPromastigotes Induced byMorinda citrifoliaLinn. Fruit (Noni) Juice Treatment

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/5063540 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Fernando Almeida-Souza ◽

Noemi Nosomi Taniwaki ◽

Ana Cláudia Fernandes Amaral ◽

Celeste da Silva Freitas de Souza ◽

Kátia da Silva Calabrese ◽

...

Keyword(s):

High Performance ◽

Fruit Juice ◽

Morinda Citrifolia ◽

Ultrastructural Changes ◽

Therapeutic Effects ◽

Lipid Inclusion ◽

Leishmanicidal Activity ◽

Transmission Electron ◽

New Treatments

The search for new treatments against leishmaniasis has increased due to high frequency of drug resistance registered in endemics areas, side effects, and complications caused by coinfection with HIV.Morinda citrifoliaLinn., commonly known as Noni, has a rich chemical composition and various therapeutic effects have been described in the literature. Studies have shown the leishmanicidal activity ofM. citrifolia; however, its action on the parasite has not yet been elucidated. In this work, we analyzed leishmanicidal activity and ultrastructural changes inLeishmania infantumpromastigotes caused byM. citrifoliafruit juice treatment.M. citrifoliafruit extract showed a yield of 6.31% and high performance liquid chromatography identified phenolic and aromatic compounds as the major constituents. IC50values were 260.5 µg/mL for promastigotes and 201.3 µg/mL for intracellular amastigotes ofL. infantumtreated withM. citrifolia. Cytotoxicity assay with J774.G8 macrophages showed thatM. citrifoliafruit juice was not toxic up to 2 mg/mL. Transmission electron microscopy showed cytoplasmic vacuolization, lipid inclusion, increased exocytosis activity, and autophagosome-like vesicles inL. infantumpromastigotes treated withM. citrifoliafruit juice.M. citrifoliafruit juice was active againstL. infantumin thein vitromodel used here causing ultrastructural changes and has a future potential for treatment against leishmaniasis.

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Migration-Inhibitory Factor Gene-Deficient Mice Are Susceptible to Cutaneous Leishmania major Infection

Infection and Immunity ◽

10.1128/iai.69.2.906-911.2001 ◽

2001 ◽

Vol 69 (2) ◽

pp. 906-911 ◽

Cited By ~ 92

Author(s):

Abhay R. Satoskar ◽

Marcelo Bozza ◽

Miriam Rodriguez Sosa ◽

Guoshing Lin ◽

John R. David

Keyword(s):

Migration Inhibitory Factor ◽

Protective Immunity ◽

Leishmania Major ◽

Inhibitory Factor ◽

Interleukin 4 ◽

Wild Type ◽

Leishmanicidal Activity ◽

Ifn Γ ◽

Deficient Mice

ABSTRACT To determine the role of endogenous migration-inhibitory factor (MIF) in the development of protective immunity against cutaneous leishmaniasis, we analyzed the course of cutaneous Leishmania major infection in MIF gene-deficient mice (MIF−/−) and wild-type (MIF+/+) mice. Following cutaneous L. major infection, MIF−/− mice were susceptible to disease and developed significantly larger lesions and greater parasite burdens than MIF+/+ mice. Interestingly, antigen-stimulated lymph node cells from MIF−/− mice produced more interleukin-4 (IL-4) and gamma interferon (IFN-γ) than those from MIF+/+ mice, although the differences were statistically not significant. IFN-γ-activated resting peritoneal macrophages from MIF−/− mice showed impaired macrophage leishmanicidal activity and produced significantly lower levels of nitric oxide and superoxide in vitro. The macrophages from MIF−/− mice, however, produced much more IL-6 than macrophages from wild-type mice. These findings demonstrate that endogenous MIF plays an important role in the development of protective immunity against L. majorin vivo. Furthermore, they indicate that the susceptibility of MIF−/− mice to L. major infection is due to impaired macrophage leishmanicidal activity rather than dysregulation of Th1 and Th2 responses.

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