Dataset Information

Lead Selection of a New Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention.

ABSTRACT: Structure-activity relationship studies of trifluoromethyl-substituted pyridine and pyrimidine analogues of 2-aminomethylphenols (JPC-2997, JPC-3186, and JPC-3210) were conducted for preclinical development for malaria treatment and/or prevention. Of these compounds, JPC-3210 [4-(tert-butyl)-2-((tert-butylamino)methyl)-6-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)phenol] was selected as the lead compound due to superior in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, lower in vitro cytotoxicity in mammalian cell lines, longer plasma elimination half-life, and greater in vivo efficacy against murine malaria.

SUBMITTER: Chavchich M

PROVIDER: S-EPMC4862471 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Lead Selection of a New Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention.

Chavchich Marina M Birrell Geoffrey W GW Ager Arba L AL MacKenzie Donna O DO Heffernan Gavin D GD Schiehser Guy A GA Jacobus Laura R LR Shanks G Dennis GD Jacobus David P DP Edstein Michael D MD

Antimicrobial agents and chemotherapy 20160422 5

Structure-activity relationship studies of trifluoromethyl-substituted pyridine and pyrimidine analogues of 2-aminomethylphenols (JPC-2997, JPC-3186, and JPC-3210) were conducted for preclinical development for malaria treatment and/or prevention. Of these compounds, JPC-3210 [4-(tert-butyl)-2-((tert-butylamino)methyl)-6-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)phenol] was selected as the lead compound due to superior in vitro antimalarial activity against multidrug-resistant Plasmodium falcipa ...[more]

PMID: 26856849

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Project description:BackgroundIn 2021, an estimated 750,000 people died from malaria. Despite this significant burden, globally, malaria incidence and mortality rates have substantially dropped over the last 30 years. However, growth in spending on malaria and improved outcomes have recently stagnated. This development has made it more important than ever to understand what constitutes efficient spending on malaria.MethodsData from various sources, including disaggregated data on malaria spending from the WHO Global Malaria Programme, National Health Accounts, and the Global Burden of Disease 2021 study was used in this study. The National Health Account report is produced at the end of a national accounting exercise that aims to map the flow of financial resources from all perspectives-incl. sources, agencies-in the health sector. Malaria spending estimates for all malaria-endemic countries from 2000 to 2020, with government and donor spending disaggregated into 11 key programme areas were generated in this study. Then, these spending estimates were combined with outcome data and estimated country efficiency using robust non-parametric stochastic frontier analysis and linear regression to examine the types of malaria spending associated with better malaria outcomes.ResultsAcross malaria-endemic countries, there is wide variation in malaria spending, with spending associated with the malaria burden within the country. Argentina, Paraguay, and Turkmenistan stood out as examples of low spending relative to their respective malaria incident per person at risk rates, while the Philippines, Guatemala, and Sri Lanka stood out as countries with case fatality ratios that were low relative to their malaria spending. Having a greater proportion of malaria spending sourced from donors or on prevention was associated with increases in incidence efficiency, while having a greater proportion of spending on anti-malarial medicines was associated with increases in case fatality efficiency.ConclusionsPrioritization of spending on prevention, anti-malarial medicines, and health systems strengthening can fight incident cases and fatalities simultaneously, especially in resource-scarce, malaria-endemic countries. Furthermore, improving the availability, frequency of collection, and quality of detailed disaggregated spending data is essential to support work that strengthens the evidence base on spending efficiency and work that improves understanding of how spending on malaria could be leveraged to bridge gaps in equity across population groups.

Project description:Internationally, the Peer Change Agent (PCA) model is the most frequently used conceptual framework for HIV prevention. Change agents themselves can be more important than the messages they convey. PCA selection is operationalized via heterogeneous methods based upon individual-level attributes. A sociometric position selection strategy, however, could increase peer influence potency and halt transmission at key network locations. In this study, we selected candidate PCAs based upon relative sociometric bridging and centrality scores and assessed their attributes in comparison to one another and to existing peer educators. We focused upon an emerging HIV epidemic among men who have sex with men in Southern India in 2011. PCAs selected based on their bridging score were more likely to be innovators when compared to other centrally-located PCAs, to PCAs located on the periphery, and to existing peer educators. We also found that sociodemographic attributes and risk behaviors were similar across all candidate PCAs, but risk behaviors of existing peer educators differed. Existing peer educators were more likely to engage in higher risk behavior such as receiving money for sex when compared to sociometrically selected peer changes agents. These existing peer educators were also more likely to exhibit leadership qualities within the overall network; they were, however, just as likely as other non-trained candidate peer change agents to report important HIV intravention behavior (encouraging condoms within their network). The importance of identifying bridges who may be able to diffuse innovation more effectively within high risk HIV networks is especially critical given recent efficacy data from novel HIV prevention interventions such as pre-exposure prophylaxis. Moreover, while existing peer educators were more likely to be leaders in our analysis, using peer educators with high risk behavior may have limited utility in enacting behavior change among sex worker peers or male clients in the network.

Dataset Information

Lead Selection of a New Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention.

Publications

Lead Selection of a New Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention.

Similar Datasets

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