Activity of anti-cancer protein kinase inhibitors against Leishmania spp. DOI Open Access

Lisa Sanderson,

Vanessa Yardley,

Simon L. Croft

et al.

Journal of Antimicrobial Chemotherapy, Journal Year: 2014, Volume and Issue: 69(7), P. 1888 - 1891

Published: March 25, 2014

There is an urgent need to develop new and effective treatments for poverty-related neglected diseases. In light of the time required bring a drug market cost involved (10–15 years, >1 billion US$), one approach identifying diseases like leishmaniasis evaluate drugs that are already registered treatment other This paper describes anti-leishmanial activities 10 FDA-approved protein kinase inhibitors available human cancers. vitro in vivo models Leishmania infection were used potency selected inhibitors. Sunitinib, sorafenib lapatinib identified as active against donovani amastigotes cultured murine macrophages with IC50 values 1.1, 3.7 2.5 μM, respectively, level similar miltefosine (IC50 = 1.0 μM), not toxic mammalian cells. addition, some L. BALB/c mouse model infection; dosing on days 7–11 50 mg/kg oral dose sunitinib, or reduced liver amastigote burdens by 41%, 36% 30%, compared untreated control mice. Although less efficacious, was also intracellular cutaneous disease-causing species amazonensis, major mexicana. study demonstrates activity clinically provides further evidence potential repurposing.

Language: Английский

Application of Dendrimers for the Treatment of Infectious Diseases DOI Creative Commons

Zandile Mhlwatika,

Blessing A. Aderibigbe

Molecules, Journal Year: 2018, Volume and Issue: 23(9), P. 2205 - 2205

Published: Aug. 31, 2018

Dendrimers are drug delivery systems that characterized by a three-dimensional, star-shaped, branched macromolecular network. They possess ideal properties such as low polydispersity index, biocompatibility and good water solubility. made up of the interior exterior layers. The layer consists functional groups useful for conjugation drugs targeting moieties. exhibits improved encapsulation efficiency, reduced toxicity, controlled release mechanisms. These unique make them delivery. have attracted considerable attention system treatment infectious diseases. diseases is hampered severely resistance. Several dendrimers their ability to overcome resistance, toxicity control mechanism encapsulated disease. aim this review discuss potentials viral parasitic infections.

Language: Английский

Citations

83
Review of the current treatments for leishmaniases DOI Creative Commons
José Ângelo Lauletta Lindoso,

Jackson Maurício Lopes Costa,

Igor Thiago Queiroz

et al.

Research and Reports in Tropical Medicine, Journal Year: 2012, Volume and Issue: unknown, P. 69 - 69

Published: July 1, 2012

Keywords: tegumentary, visceral, therapy, HIV

Language: Английский

Citations

77
Antileishmanial activity of diterpene acids in copaiba oil DOI Creative Commons
Adriana O. Santos,

Érika Izumi,

Tânia Ueda‐Nakamura

et al.

Memórias do Instituto Oswaldo Cruz, Journal Year: 2013, Volume and Issue: 108(1), P. 59 - 64

Published: Feb. 1, 2013

Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against based on pentavalent antimonials, which were developed more than century ago. The goals this study investigate antileishmanial activity diterpene acids in copaiba oil, as well some possible targets their action Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic polyaltic isolated from Copaifera officinales oleoresins utilised. Ultrastructural changes specific organelle diterpenes investigated with electron microscopy flow cytometry, respectively. All compounds had level L. Hydroxycopalic acid methyl demonstrated most promastigotes 50% inhibitory concentration (IC50) values 2.5 6.0 µg/mL, However, kaurenoic axenic amastigote IC50 3.5 4.0 Agathic, caused significant increases plasma membrane permeability mitochondrial depolarisation protozoan. In conclusion, oil its should be explored for development drugs.

Language: Английский

Citations

77
Terpenes Increase the Lipid Dynamics in the Leishmania Plasma Membrane at Concentrations Similar to Their IC50 Values DOI Creative Commons

Heverton Silva Camargos,

Rodrigo Alves Moreira,

Sebastião Antônio Mendanha

et al.

PLoS ONE, Journal Year: 2014, Volume and Issue: 9(8), P. e104429 - e104429

Published: Aug. 7, 2014

Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in plasma membrane terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×10(6) parasites/mL, sesquiterpene nerolidol monoterpenes (+)-limonene, α-terpineol 1,8-cineole inhibited growth parasites with IC50 values 0.008, 0.549, 0.678 4.697 mM, respectively. The these increased as parasite concentration used cytotoxicity increased, this behavior was examined a theoretical treatment experimental data. Cytotoxicity tests same EPR experiments correlation between concentrations at which they altered fluidity. In addition, induced small amounts cell lysis (4-9%) their respective values. assays high (2×10(9) parasites/mL), incorporation terpene into very fast, observed for 24 h 5 min-incubation periods were significantly different. Taken together, results suggest that associated attack on parasite. vitro similar to miltefosine, has hydrophobicity; thus, might be drug delivery systems, such lipid nanoparticles treat leishmaniasis.

Language: Английский

Citations

71
Synthesis and biological evaluation of novel 2,3-disubstituted quinoxaline derivatives as antileishmanial and antitrypanosomal agents DOI
Juliana Cogo, Vanessa Kaplum, Diego Pereira Sangi

et al.

European Journal of Medicinal Chemistry, Journal Year: 2014, Volume and Issue: 90, P. 107 - 123

Published: Nov. 11, 2014

Language: Английский

Citations

70
Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites DOI Creative Commons

Sanjay Varikuti,

Bijay Kumar Jha, Greta Volpedo

et al.

Frontiers in Microbiology, Journal Year: 2018, Volume and Issue: 9

Published: Nov. 30, 2018

The neglected tropical diseases (NTDs) caused by protozoan parasites are a major global health problem and responsible for significant morbidity mortality. Current treatments using anti-parasitic drugs toxic prolonged with poor patient compliance. In addition, emergence of drug-resistant is rapidly increasing worldwide. Hence, there strong need safer better therapeutics these infections. Host-directed therapy that target host pathways required pathogen survival or its clearance considered as promising approach treating This review will give summary current status advances host-targeted therapies NTDs protozoa.

Language: Английский

Citations

65
Leishmaniasis: treatment, drug resistance and emerging therapies DOI
Shyam Sundar, Jaya Chakravarty,

Lalit Prashant Meena

et al.

Expert Opinion on Orphan Drugs, Journal Year: 2018, Volume and Issue: 7(1), P. 1 - 10

Published: Dec. 5, 2018

Introduction: Leishmaniasis is one of the most neglected tropical infectious diseases in world. Emergence drug resistance and toxicity high cost available drugs with lack new antileishmanial highlight need to search for newer molecules activities.Areas covered: This article describes currently their risk developing discusses therapies. These include oral lipid-based formulations amphotericin B, use different delivery systems, quinolone derivatives – naphthoquinone, buparvaquone, etc.Expert opinion: There are only a handful drugs, even fewer pipeline. Guideline-based treatment, proper selection compound, should be practiced. Combination therapy used preferably prevent or delay resistance. As patients PKDL (post-kala-azar dermal leishmaniasis) asymptomatic, it important that shorter regimens developed, which will encourage opt complete treatment. Pharmaceutical industry "not profit' organizations encouraged enhance efforts finding clinically effective drugs.

Language: Английский

Citations

64
Current and emerging therapies for the treatment of leishmaniasis DOI Creative Commons
Shyam Sundar, Jitendra Singh, Vishal Singh

et al.

Expert Opinion on Orphan Drugs, Journal Year: 2024, Volume and Issue: 12(1), P. 19 - 32

Published: March 26, 2024

Introduction Leishmaniasis, a neglected protozoan illness caused by kinetoplastid pathogens encompasses three major clinical subtypes: visceral, cutaneous and mucocutaneous leishmaniasis. Pentavalent antimonials (SbV) have long been the preferred treatment worldwide but increased drug resistance, significant side effects, including cardiotoxicity limited their use, particularly in visceral leishmaniasis India. Similarly, other approved alternatives concerns such as teratogenicity, high cost, resistance.

Language: Английский

Citations

7
Synthesis and biological evaluation of 2,3-diarylimidazo[1,2-a]pyridines as antileishmanial agents DOI

Sophie Marhadour,

Pascal Marchand, Fabrice Pagniez

et al.

European Journal of Medicinal Chemistry, Journal Year: 2012, Volume and Issue: 58, P. 543 - 556

Published: Nov. 2, 2012

Language: Английский

Citations

65
4-Acetoxydolastane Diterpene from the Brazilian Brown Alga Canistrocarpus cervicornis as Antileishmanial Agent DOI Creative Commons
Adriana O. Santos,

Elizandra Aparecida Britta,

Έverson Miguel Bianco

et al.

Marine Drugs, Journal Year: 2011, Volume and Issue: 9(11), P. 2369 - 2383

Published: Nov. 11, 2011

Natural marine products have shown an interesting array of diverse and novel chemical structures with potent biological activities. Our study reports the antiproliferative assays crude extracts, fraction pure compound (4R,9S,14S)-4α-acetoxy-9β,14α-dihydroxydolast-1(15),7-diene (1) obtained from brown alga Canistrocarpus cervicornis showing antileishmanial activity. We showed that 1 had a dose-dependent activity during 72 h treatment, exhibiting IC(50) 2.0 μg/mL, 12.0 4.0 μg/mL for promastigote, axenic amastigote intracellular forms Leishmania amazonensis, respectively. A cytotoxicity assay action isolated was 93.0 times less toxic to macrophage than protozoan. Additionally, induced ultrastructural changes, including extensive mitochondrial damage; decrease in Rh123 fluorescence, suggesting interference membrane potential; lipid peroxidation parasite cells. The use C. against L. amazonensis parasites might be great interest as future alternative development new drugs.

Language: Английский

Citations

65