Special Issue "Emerging Treatment Options to Fight Malaria: New Compounds and Drug Combinations"

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: 28 September 2023 | Viewed by 1595

Special Issue Editors

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
Interests: infectious diseases; bacterial infections; viral infections; antibiotic stewardship
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite unsuccessful eradication attempts, control efforts to avoid infections, and artemisinin-based therapies, the global burden of malaria remains high, with 430,000 deaths every year and 200 million cases. Unfortunately, children represent a high proportion of new diagnoses.

Over the last few years, renewed attempts to control the disease have reduced the prevalence of malaria by over 50%, raising the prospect that elimination and perhaps eradication may be a long-term possibility.

Achievement of this goal requires the development of new tools, including efficacious vaccines as well as a precise understanding of the pathophysiology and biology of the parasite, and especially novel antimalarial drugs and combinations which could safely ensure the rapid clearance of infection as well as a durable cure without recurrence. In addition, the development of resistance to past and present anti-malarial drugs, especially artemisinin-based regimes, highlights the need for continued research to stay one step ahead, specifically to treat severe complications such as cerebral malaria.

Multiple approaches to develop new antimalarial medications, ranging from modifications of existing agents to the design of novel agents targeting novel targets, already exist.

Modern advances in parasite biology knowledge, along with the availability of various genomic techniques, represent several novel targets for the elaboration of new therapies.

This Special Issue aims to collect original articles, literature reviews, and case reports/case series on emerging treatment options against malaria, with particular interest on new compounds, either experimental or under research, and drug combinations.

Dr. Nicolò Musso
Dr. Andrea Marino
Guest Editors

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  • Malaria
  • antimalarial drugs
  • severe malaria
  • resistant malaria
  • treatment

Published Papers (1 paper)

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Rational-Based Discovery of Novel β-Carboline Derivatives as Potential Antimalarials: From In Silico Identification of Novel Targets to Inhibition of Experimental Cerebral Malaria
Pathogens 2022, 11(12), 1529; https://doi.org/10.3390/pathogens11121529 - 13 Dec 2022
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Malaria is an infectious disease widespread in underdeveloped tropical regions. The most severe form of infection is caused by Plasmodium falciparum, which can lead to development of cerebral malaria (CM) and is responsible for deaths and significant neurocognitive sequelae throughout life. In [...] Read more.
Malaria is an infectious disease widespread in underdeveloped tropical regions. The most severe form of infection is caused by Plasmodium falciparum, which can lead to development of cerebral malaria (CM) and is responsible for deaths and significant neurocognitive sequelae throughout life. In this context and considering the emergence and spread of drug-resistant P. falciparum isolates, the search for new antimalarial candidates becomes urgent. β-carbolines alkaloids are good candidates since a wide range of biological activity for these compounds has been reported. Herein, we designed 20 chemical entities and performed an in silico virtual screening against a pool of P. falciparum molecular targets, the Brazilian Malaria Molecular Targets (BRAMMT). Seven structures showed potential to interact with PfFNR, PfPK7, PfGrx1, and PfATP6, being synthesized and evaluated for in vitro antiplasmodial activity. Among them, compounds 36 and 10 inhibited the growth of the W2 strain at µM concentrations, with low cytotoxicity against the human cell line. In silico physicochemical and pharmacokinetic properties were found to be favorable for oral administration. The compound 10 provided the best results against CM, with important values of parasite growth inhibition on the 5th day post-infection for both curative (67.9%) and suppressive (82%) assays. Furthermore, this compound was able to elongate mice survival and protect them against the development of the experimental model of CM (>65%). Compound 10 also induced reduction of the NO level, possibly by interaction with iNOS. Therefore, this alkaloid showed promising activity for the treatment of malaria and was able to prevent the development of experimental cerebral malaria (ECM), probably by reducing NO synthesis. Full article
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