scholarly journals In Silico Investigation of Flavonoids as Potential Trypanosomal Nucleoside Hydrolase Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Christina Hung Hung Ha ◽  
Ayesha Fatima ◽  
Anand Gaurav

Human African Trypanosomiasis is endemic to 37 countries of sub-Saharan Africa. It is caused by two related species of Trypanosoma brucei. Current therapies suffer from resistance and public accessibility of expensive medicines. Finding safer and effective therapies of natural origin is being extensively explored worldwide. Pentamidine is the only available therapy for inhibiting the P2 adenosine transporter involved in the purine salvage pathway of the trypanosomatids. The objective of the present study is to use computational studies for the investigation of the probable trypanocidal mechanism of flavonoids. Docking experiments were carried out on eight flavonoids of varying level of hydroxylation, namely, flavone, 5-hydroxyflavone, 7-hydroxyflavone, chrysin, apigenin, kaempferol, fisetin, and quercetin. Using AutoDock 4.2, these compounds were tested for their affinity towards inosine-adenosine-guanosine nucleoside hydrolase and the inosine-guanosine nucleoside hydrolase, the major enzymes of the purine salvage pathway. Our results showed that all of the eight tested flavonoids showed high affinities for both hydrolases (lowest free binding energy ranging from −10.23 to −7.14 kcal/mol). These compounds, especially the hydroxylated derivatives, could be further studied as potential inhibitors of the nucleoside hydrolases.

2017 ◽  
Vol 1 (6) ◽  
pp. 533-537
Author(s):  
Lorenz von Seidlein ◽  
Borimas Hanboonkunupakarn ◽  
Podjanee Jittmala ◽  
Sasithon Pukrittayakamee

RTS,S/AS01 is the most advanced vaccine to prevent malaria. It is safe and moderately effective. A large pivotal phase III trial in over 15 000 young children in sub-Saharan Africa completed in 2014 showed that the vaccine could protect around one-third of children (aged 5–17 months) and one-fourth of infants (aged 6–12 weeks) from uncomplicated falciparum malaria. The European Medicines Agency approved licensing and programmatic roll-out of the RTSS vaccine in malaria endemic countries in sub-Saharan Africa. WHO is planning further studies in a large Malaria Vaccine Implementation Programme, in more than 400 000 young African children. With the changing malaria epidemiology in Africa resulting in older children at risk, alternative modes of employment are under evaluation, for example the use of RTS,S/AS01 in older children as part of seasonal malaria prophylaxis. Another strategy is combining mass drug administrations with mass vaccine campaigns for all age groups in regional malaria elimination campaigns. A phase II trial is ongoing to evaluate the safety and immunogenicity of the RTSS in combination with antimalarial drugs in Thailand. Such novel approaches aim to extract the maximum benefit from the well-documented, short-lasting protective efficacy of RTS,S/AS01.


1993 ◽  
Vol 47 (3) ◽  
pp. 555-556
Author(s):  
Lado Ruzicka

Crisis ◽  
2011 ◽  
Vol 32 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Eugene Kinyanda ◽  
Ruth Kizza ◽  
Jonathan Levin ◽  
Sheila Ndyanabangi ◽  
Catherine Abbo

Background: Suicidal behavior in adolescence is a public health concern and has serious consequences for adolescents and their families. There is, however, a paucity of data on this subject from sub-Saharan Africa, hence the need for this study. Aims: A cross-sectional multistage survey to investigate adolescent suicidality among other things was undertaken in rural northeastern Uganda. Methods: A structured protocol administered by trained psychiatric nurses collected information on sociodemographics, mental disorders (DSM-IV criteria), and psychological and psychosocial risk factors for children aged 3–19 years (N = 1492). For the purposes of this paper, an analysis of a subsample of adolescents (aged 10–19 years; n = 897) was undertaken. Results: Lifetime suicidality in this study was 6.1% (95% CI, 4.6%–7.9%). Conclusions: Factors significantly associated with suicidality included mental disorder, the ecological factor district of residence, factors suggestive of low socioeconomic status, and disadvantaged childhood experiences.


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