scholarly journals Effect of Praziquantel on Schistosoma mekongi Proteome and Phosphoproteome

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 417
Author(s):  
Peerut Chienwichai ◽  
Sumate Ampawong ◽  
Poom Adisakwattana ◽  
Tipparat Thiangtrongjit ◽  
Yanin Limpanont ◽  
...  
Keyword(s):  
Drug Development ◽  
Kinase Inhibitors ◽  
Src Kinase ◽  
Spectrometric Data ◽  
Kinase Substrate ◽  
Bioinformatic Tools ◽  
Schistosoma Mekongi ◽  
Alternative Approaches ◽  
Novel Drug ◽  
And Oxidative Stress

Schistosoma mekongi causes schistosomiasis in southeast Asia, against which praziquantel (PZQ) is the only treatment option. PZQ resistance has been reported, thus increasing the requirement to understand mechanism of PZQ. Herein, this study aimed to assess differences in proteome and phosphoproteome of S. mekongi after PZQ treatment for elucidating its action. Furthermore, key kinases related to PZQ effects were predicted to identify alternative targets for novel drug development. Proteomes of S. mekongi were profiled after PZQ treatment at half maximal inhibitory concentration and compared with untreated worms. A total of 144 proteins were differentially expressed after treatment. In parallel, immunohistochemistry indicated a reduction of phosphorylation, with 43 phosphoproteins showing reduced phosphorylation, as identified by phosphoproteomic approach. Pathway analysis of mass spectrometric data showed that calcium homeostasis, worm antigen, and oxidative stress pathways were influenced by PZQ treatment. Interestingly, two novel mechanisms related to protein folding and proteolysis through endoplasmic reticulum-associated degradation pathways were indicated as a parasiticidal mechanism of PZQ. According to kinase–substrate predictions with bioinformatic tools, Src kinase was highlighted as the major kinase related to the alteration of phosphorylation by PZQ. Interfering with these pathways or applying Src kinase inhibitors could be alternative approaches for further antischistosomal drug development.

Src Kinase Inhibitors: Promising Cancer Therapeutics?

2012 ◽  
Vol 17 (2) ◽  
pp. 145-159 ◽  
Author(s):  
Helen Creedon ◽  
Valerie G . Brunton
Keyword(s):  
Kinase Inhibitors ◽  
Src Kinase ◽  
Cancer Therapeutics

scholarly journals Innovative solutions to novel drug development in mental health

2013 ◽  
Vol 37 (10) ◽  
pp. 2438-2444 ◽  
Author(s):  
T.R. Insel ◽  
V. Voon ◽  
J.S. Nye ◽  
V.J. Brown ◽  
B.M. Altevogt ◽  
...  
Keyword(s):  
Mental Health ◽  
Drug Development ◽  
Innovative Solutions ◽  
Novel Drug

scholarly journals Identification of Heparin Modifications and Polysaccharide Inhibitors of Plasmodium falciparum Merozoite Invasion That Have Potential for Novel Drug Development

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Michelle J. Boyle ◽  
Mark Skidmore ◽  
Benjamin Dickerman ◽  
Lynsay Cooper ◽  
Anthony Devlin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Development ◽  
Inhibitory Activity ◽  
Sulfated Polysaccharides ◽  
Merozoite Invasion ◽  
Content Type ◽  
Molecular Weights ◽  
Falciparum Merozoite ◽  
Successful Control ◽  
Novel Drug

ABSTRACT Despite recent successful control efforts, malaria remains a leading global health burden. Alarmingly, resistance to current antimalarials is increasing and the development of new drug families is needed to maintain malaria control. Current antimalarials target the intraerythrocytic developmental stage of the Plasmodium falciparum life cycle. However, the invasive extracellular parasite form, the merozoite, is also an attractive target for drug development. We have previously demonstrated that heparin-like molecules, including those with low molecular weights and low anticoagulant activities, are potent and specific inhibitors of merozoite invasion and blood-stage replication. Here we tested a large panel of heparin-like molecules and sulfated polysaccharides together with various modified chemical forms for their inhibitory activity against P. falciparum merozoite invasion. We identified chemical modifications that improve inhibitory activity and identified several additional sulfated polysaccharides with strong inhibitory activity. These studies have important implications for the further development of heparin-like molecules as antimalarial drugs and for understanding merozoite invasion.

Src Kinase Inhibitors: An Update on Patented Compounds

2011 ◽  
Vol 18 (33) ◽  
pp. 5061-5078 ◽  
Author(s):  
S. Schenone ◽  
C. Brullo ◽  
F. Musumeci ◽  
M. Radi ◽  
D. Castagnolo
Keyword(s):  
Kinase Inhibitors ◽  
Src Kinase

3D-QSAR studies on c-Src kinase inhibitors and docking analyses of a potent dual kinase inhibitor of c-Src and c-Abl kinases

2005 ◽  
Vol 13 (15) ◽  
pp. 4704-4712 ◽  
Author(s):  
Ram Thaimattam ◽  
Pankaj R. Daga ◽  
Rahul Banerjee ◽  
Javed Iqbal
Keyword(s):  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Src Kinase ◽  
3D Qsar ◽  
Qsar Studies ◽  
Abl Kinases

scholarly journals Harnessing the medicinal properties of Cussonia barteri Seem. (Araliaceae) in drug development. A review

2018 ◽  
Vol 64 (3) ◽  
pp. 50-61 ◽  
Author(s):  
Ighodaro Igbe ◽  
Osaze Edosuyi ◽  
Agbonlahor Okhuarobo
Keyword(s):  
Drug Development ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Stem Bark ◽  
Deciduous Tree ◽  
Drug Candidates ◽  
Medicinal Properties ◽  
Phytochemical Constituents ◽  
Anti Inflammatory ◽  
Novel Drug

Summary Cussonia barteri Seem (Araliaceae) is a deciduous tree growing in savannah of Africa. Ethnomedicinally, it is used in Africa as an analgesic, anti-malarial, anti-inflammatory, anti-anaemic, anti-diarhoea, anti-poison, ani-pyschotic and anti-epileptic agent. This review provides a brief summary on the phytochemical screenings, ethnomedicinal and pharmacological applications of various parts of C. barteri. Leaves, stem bark and seed of C. barteri have been shown to be rich in saponins, flavonoids, phenols, sugars and alkaloids. Some of these constituents have been isolated and elucidated from C. barteri. Several compounds isolated from plant include triterpenes, saponins, polyenyne and quinic esters. Phytochemical constituents are also partly responsible for biological activities of C. barteri. Extracts and components isolated from the plant have demonstrated neuropharmacological, anti-larvicidal, anti-microbial, anti-inflammatory and antioxidant activities. Overall, the insights provided by this review reinforce the potential of C. barteri for drug development and create the need for further scientific probe of constituents of the plant with the aim of developing novel drug candidates.

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