Multi-omics approaches to improve malaria therapy

2021 ◽  
Vol 167 ◽  
pp. 105570
Author(s):  
Min Zhou ◽  
Ayşegül Varol ◽  
Thomas Efferth
Keyword(s):  
2020 ◽  
Vol 16 (3) ◽  
pp. 392-402
Author(s):  
Christiaan W. van der Westhuyzen ◽  
Richard K. Haynes ◽  
Jenny-Lee Panayides ◽  
Ian Wiid ◽  
Christopher J. Parkinson

Background: With few exceptions, existing tuberculosis drugs were developed many years ago and resistance profiles have emerged. This has created a need for new drugs with discrete modes of action. There is evidence that tuberculosis (like other bacteria) is susceptible to oxidative pressure and this has yet to be properly utilised as a therapeutic approach in a manner similar to that which has proven highly successful in malaria therapy. Objective: To develop an alternative approach to the incorporation of bacterial siderophores that results in the creation of antitubercular peroxidic leads for subsequent development as novel agents against tuberculosis. Methods: Eight novel peroxides were prepared and the antitubercular activity (H37Rv) was compared to existing artemisinin derivatives in vitro. The potential for toxicity was evaluated against the L6 rat skeletal myoblast and HeLa cervical cancer lines in vitro. Results: The addition of a pyrimidinyl residue to an artemisinin or, preferably, a tetraoxane peroxidic structure results in antitubercular activity in vitro. The same effect is not observed in the absence of the pyrimidine or with other heteroaromatic substituents. Conclusion: The incorporation of a pyrimidinyl residue adjacent to the peroxidic function in an organic peroxide results in anti-tubercular activity in an otherwise inactive peroxidic compound. This will be a useful approach for creating oxidative drugs to target tuberculosis.


Author(s):  
Mohammad Abid ◽  
Shailja Singh ◽  
Timothy J. Egan ◽  
Mukesh C. Joshi

Apicomplexian parasite of the genus Plasmodium is the causative agent of malaria, one of the most devastating, furious and common infectious disease throughout the world. According to the latest World malaria report, there were 229 million cases of malaria in 2019 majorly consisting of children under 5 years of age. Some of known analogues viz. quinine, quinoline-containing compounds have been used for last century in the clinical treatment of malaria. Past few decades have witnessed the emergence of multi-drug resistance (MDR) strains of Plasmodium species to existing antimalarials pressing the need for new drug candidates. For the past few decades bioorganometallic approach to malaria therapy has been introduced which led to the discovery of noval metalcontaining aminoquinolines analogues viz. ferroquine (FQ or 1), Ruthenoquine (RQ or 2) and other related potent metal-analogues. It observed that some metal containing analogues (Fe-, Rh-, Ru-, Re-, Au-, Zn-, Cr-, Pd-, Sn-, Cd-, Ir-, Co-, Cu-, and Mn-aminoquines) were more potent; however, some were equally potent as Chloroquine (CQ) and 1. This is probably due to the intertion of metals in the CQ via various approaches, which might be a very attractive strategy to develop a SAR of novel metal containing antimalarials. Thus, this review aims to summarize the SAR of metal containing aminoquines towards the discovery of potent antimalarial hybrids to provide an insight for rational designs of more effective and less toxic metal containing amoniquines.


1935 ◽  
Vol 31 (11-12) ◽  
pp. 1338-1339
Author(s):  
I. Galant

While Volume I of the Proceedings of the Ural Psychoneurological Institute presents Malkin's excellent monograph on the malaria therapy of psychoses, Volume II is not uniform in its subject matter, containing sixteen articles on various burning issues of psychiatry. The organization of in-patient and out-patient psychotherapy, the treatment of psychoses, and questions of clinical psychiatry and neuropathology are the contents of this collection, which is rich not so much in quantity as in quality, a merit not every collection of works can be proud of.


2009 ◽  
Vol 83 (22) ◽  
pp. 11979-11982 ◽  
Author(s):  
Jackie Pallister ◽  
Deborah Middleton ◽  
Gary Crameri ◽  
Manabu Yamada ◽  
Reuben Klein ◽  
...  

ABSTRACT Hendra virus and Nipah virus, two zoonotic paramyxoviruses in the genus Henipavirus, have recently emerged and continue to cause sporadic disease outbreaks in humans and animals. Mortality rates of up to 75% have been reported in humans, but there are presently no clinically licensed therapeutics for treating henipavirus-induced disease. A recent report indicated that chloroquine, used in malaria therapy for over 70 years, prevented infection with Nipah virus in vitro. Chloroquine was assessed using a ferret model of lethal Nipah virus infection and found to be ineffective against Nipah virus infection in vivo.


2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Bartholomew Yir-Erong ◽  
Marcel Tunkumgnen Bayor ◽  
Isaac Ayensu ◽  
Stephen Yao Gbedema ◽  
Joshua Boateng

Background. The study was undertaken to elicit the knowledge, views, and perceptions of key stakeholders on malaria, its bioburden, and treatment options, in order to ascertain the knowledge gabs and challenges, especially in the use of oral quinine in childhood malaria. Methods. A cross-sectional survey was conducted using a well-structured Likert Scale and self-administered questionnaire. The principal site of the study was a government-run children’s hospital located in the Ashiedu Keteke Sub-Metro of Accra. The study population included health workers, parents, and guardians or care givers. The participants were 300, purposively selected, and consisted of both men (41%) and women (59%) who were twenty years and above, whether employed (42%), self-employed (37%), or unemployed (21%). Results. Majority of the participants (78%) demonstrated above average knowledge of malaria. However, their awareness of the causes, modes of transmission, signs, and symptoms as well as preventive mechanisms of malaria did not result in low incidence of malaria. About 77% of the respondents agreed they would seek treatment within 24 hours once signs and symptoms are detected. Though close to 50% undertook home treatment of malaria, majority eventually sought treatment at hospital or clinic. Above 92% of respondents knew that quinine is used to treat malaria and agreed its bitter taste greatly affects compliance, especially in children. Consequently, 95% of the respondents would be glad if its bitter taste is masked. Conclusion. The study demonstrated the availability of substantial knowledge of the devastating effects of malaria, especially in children. Therefore, there is the need to ensure the availability and utilization of effective paediatric formulations in the fight against malaria. From this study, fast dissolving oral thin film with a good mouth feel, would be the formulation of choice for quinine.


2021 ◽  
Vol 15 (1) ◽  
pp. 282-292
Author(s):  
Babatunde Samuel ◽  
Yemi Adekola Adekunle

Emergence of malaria parasite resistance to drugs has raised global public health concerns for a compelling need to develop improved malaria therapy. This study is a bio-guided isolation of triterpenoid antimalarial compounds from Terminalia mantaly. Methanol extract of the plant was subjected to column chromatography, and eluted with a ternary solvent system gradient-wise. Two compounds, 1 and 2, were isolated and characterised by spectroscopic data (IR, 1H and 13C NMR, COSY, HMQC, HMBC) and by comparison with literature. Isolated compounds were investigated for antimalarial property by spectrophotometric determination of inhibition of β-Hematin formation, absorbance taken at 405 nm. Results were analysed using Graghpad Prism® (6.0) and presented as mean IC50±SEM. Statistical significance, determined using Student’s t-test and one-way ANOVA, set at p-value of 0.05. Quantitative β-Hematin formation inhibitory activities gave IC50±SEM values of (compound 1; 4.434±0.47), (compound 2; 5.140±4.2) with (chloroquine; 0.335±0.1 mg/ml). Compound 1 was identified as 2,3,19,23-tetrahydroxyolean-12-en-28-oic acid glucopyranoside (arjunglucoside I), and compound2 as its aglycone, 2,3,19,23-tetrahydroxyolean-12-en-28-oic acid (arjungenin). This study provided credence for folkloric use of Terminalia mantaly to treat malaria, and this observed activity was probably due to these isolated triterpenoids.Keywords: β-Hematin, triterpenoids, nuclear magnetic resonance spectroscopy


2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Tiphaine Gaillard ◽  
Marylin Madamet ◽  
Francis Foguim Tsombeng ◽  
Jérôme Dormoi ◽  
Bruno Pradines
Keyword(s):  

Sign in / Sign up

Export Citation Format

Share Document