We have located links that may give you full text access.
Cheminformatic Analysis of Antimalarial Chemical Space Illuminates Therapeutic Mechanisms and Offers Strategies for Therapy Development.
Journal of Chemical Information and Modeling 2017 September 26
The clear and present danger of malaria, which has been amplified in recent years by climate change, and the progressive thinning of our drug arsenal over the past two decades raise uncomfortable questions about the current state and future of antimalarial drug development. Besides suffering from many of the same technical challenges that affect drug development in other disease areas, the quest for new antimalarial therapies is also hindered by the complex, dynamic life cycle of the malaria parasite, P. falciparum, in its mosquito and human hosts, and its role thereof in the elicitation of drug resistance. New strategies are needed in order to ensure economical and expeditious development of new, more efficacious treatments. In the present study, we employ open-source cheminformatics tools to analyze the chemical space traversed by approved antimalarial drugs and promising candidates at various stages of development to uncover insights that could shape future endeavors in the field. Our scaffold-centric analysis reveals that the antimalarial chemical space is disjointed and segregated into a few dominant structural groups. In fact, the structures of antimalarial drugs and drug candidates are distributed according to Pareto's principle. This structural convergence can potentially be exploited for future drug discovery by incorporating it into bioinformatics workflows that are typically employed for solving problems in structural biology. Significantly, we demonstrate how molecular scaffold hunting can be applied to unearth putative mechanisms of action of drugs whose activities remain a mystery, and how scaffold-centric analysis of drug space can also provide a recipe for combination therapies that minimize the likelihood of emergence of drug resistance, as well as identify areas on which to focus efforts. Finally, we also observe that over half of the molecules in the antimalarial space bear no resemblance to other molecules in the collection, which suggests that the pharmacobiology of antimalarial drugs has not been entirely surveyed.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app