Drug Resistance in Leishmaniasis: Current Drug-Delivery Systems and Future Perspectives

Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul

doi:10.4155/fmc.13.143

Cited by 74 publications

(45 citation statements)

References 110 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Leishmaniasis is a collective term for different tropical diseases all caused by different Leishmania species. Drug treatment is often toxic for the human host and more and more resistances occur [105].…”

Section: Inositol Transporters Of Protozoan Pathogensmentioning

confidence: 99%

Inositol transport proteins

Schneider

2015

FEBS Letters

View full text Add to dashboard Cite

a b s t r a c tThe cyclic polyol myo-inositol is a key molecule in many different metabolic pathways among all organisms; in addition, it is fundamental for osmotic balance in the mammalian brain. This review sums up inositol transporters from eukaryotic organisms, elucidating their vital role in regulating the intracellular distribution and uptake of inositol. They can be divided into two groups according to their transport mechanisms: (1) sodium ion coupled inositol transporters that belong to the Solute Carrier Families 5 and 6-like Superfamily and, (2) proton coupled inositol symporters that are members of the Major Facilitator Superfamily. Intriguingly members of both families offer promising targets for medical treatment of a variety of diseases.

show abstract

Section: Inositol Transporters Of Protozoan Pathogensmentioning

confidence: 99%

Inositol transport proteins

Schneider

2015

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…Furthermore, they present several problems, including toxicity, many adverse side effects, and high costs. The most relevant problem is related to the fact that many of these drugs were developed many years ago, and currently, there are resistant strains (4).…”

mentioning

confidence: 99%

Novel Heteroaryl Selenocyanates and Diselenides as Potent Antileishmanial Agents

Baquedano

Alcolea

Toro

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

A series of new selenocyanates and diselenides bearing interesting bioactive scaffolds (quinoline, quinoxaline, acridine, chromene, furane, isosazole, etc.) was synthesized, and their in vitro leishmanicidal activities against Leishmania infantum amastigotes along with their cytotoxicities in human THP-1 cells were determined. Interestingly, most tested compounds were active in the low micromolar range and led us to identify four lead compounds (1h, 2d, 2e, and 2f) with 50% effective dose (ED 50 ) values ranging from 0.45 to 1.27 M and selectivity indexes of >25 for all of them, much higher than those observed for the reference drugs. These active derivatives were evaluated against infected macrophages, and in order to gain preliminary knowledge about their possible mechanism of action, the inhibition of trypanothione reductase (TryR) was measured. Among these novel structures, compounds 1h (3,5-dimethyl-4-isoxazolyl selenocyanate) and 2d [3,3=-(diselenodiyldimethanediyl)bis(2-bromothiophene)] exhibited good association between TryR inhibitory activity and antileishmanial potency, pointing to 1h, for its excellent theoretical ADME (absorption, distribution, metabolism, and excretion) properties, as the most promising lead molecule for leishmancidal drug design.

show abstract

“…[6][7][8] Many of the parasites portray resistance to drugs currently in practice for Leishmania therapy. [9] Moreover, most of the drugs reportedly have side-effects and toxicity. [10,11] Thus, there is a need to develop new therapeutic regimes with better antileishmanial properties and lower side-effects.…”

Section: Masoom Yasinzaimentioning

confidence: 99%

In‐vitroantileishmanial potential of peptide drug hirudin

et al. 2016

Self Cite

View full text Add to dashboard Cite

Hirudin is clinically an important drug used for the treatment of cardiac diseases, but has never been elucidated for antileishmanial potential. This study was designed to determine the therapeutic utility of hirudin against leishmaniasis. Binding affinities of 28 potent proteinase inhibitors were screened computationally against leishmanolysin (GP63), out of which hirudin exhibited higher binding affinity with GP63 and good expected IC values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC values of 0.60 ± 0.36 μg/mL and 0.43 ± 0.23 μg/mL, respectively, in a dose- and time-dependent assay. The cytotoxicity assay revealed no adverse effects on human macrophages with LD value of 860.11 ± 53.44 μg/mL. Hirudin caused leishmanial cell death mainly by apoptosis and membrane permeability. In spite of the basic knowledge obtained, hirudin mechanism is considerably less prone to the induction of resistance than classical drugs. Collectively, this study fosters further studies for the hirudin as new antileishmania lead with a new mode of action.

show abstract

Drug Resistance in Leishmaniasis: Current Drug-Delivery Systems and Future Perspectives

Cited by 74 publications

References 110 publications

Inositol transport proteins

Inositol transport proteins

Novel Heteroaryl Selenocyanates and Diselenides as Potent Antileishmanial Agents

In‐vitroantileishmanial potential of peptide drug hirudin

Contact Info

Product

Resources

About