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Nature Reviews. Drug Discovery Oct 2023Recent antimalarial drug discovery has been a race to produce new medicines that overcome emerging drug resistance, whilst considering safety and improving dosing... (Review)
Review
Recent antimalarial drug discovery has been a race to produce new medicines that overcome emerging drug resistance, whilst considering safety and improving dosing convenience. Discovery efforts have yielded a variety of new molecules, many with novel modes of action, and the most advanced are in late-stage clinical development. These discoveries have led to a deeper understanding of how antimalarial drugs act, the identification of a new generation of drug targets, and multiple structure-based chemistry initiatives. The limited pool of funding means it is vital to prioritize new drug candidates. They should exhibit high potency, a low propensity for resistance, a pharmacokinetic profile that favours infrequent dosing, low cost, preclinical results that demonstrate safety and tolerability in women and infants, and preferably the ability to block Plasmodium transmission to Anopheles mosquito vectors. In this Review, we describe the approaches that have been successful, progress in preclinical and clinical development, and existing challenges. We illustrate how antimalarial drug discovery can serve as a model for drug discovery in diseases of poverty.
Topics: Animals; Female; Humans; Antimalarials; Plasmodium; Drug Resistance; Drug Discovery
PubMed: 37652975
DOI: 10.1038/s41573-023-00772-9 -
International Journal For Parasitology Jul 2023
Topics: Anthelmintics; Vaccines; Drug Resistance
PubMed: 37257805
DOI: 10.1016/j.ijpara.2023.05.004 -
Biomedicine & Pharmacotherapy =... Jul 2023Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral... (Review)
Review
Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds.
Topics: Humans; Artemisinins; Antimalarials; Malaria
PubMed: 37182516
DOI: 10.1016/j.biopha.2023.114866 -
International Journal of Molecular... Aug 2023Saponins are a diverse group of naturally occurring plant secondary metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea... (Review)
Review
Saponins are a diverse group of naturally occurring plant secondary metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea creatures. They consist of a hydrophilic sugar moiety linked to a lipophilic aglycone, resulting in an amphiphilic nature and unique functional properties. Their amphiphilic structures enable saponins to exhibit surface-active properties, resulting in stable foams and complexes with various molecules. In the context of food applications, saponins are utilized as natural emulsifiers, foaming agents, and stabilizers. They contribute to texture and stability in food products and have potential health benefits, including cholesterol-lowering and anticancer effects. Saponins possess additional bioactivities that make them valuable in the pharmaceutical industry as anti-inflammatory, antimicrobial, antiviral, and antiparasitic agents to name a few. Saponins can demonstrate cytotoxic activity against cancer cell lines and can also act as adjuvants, enhancing the immune response to vaccines. Their ability to form stable complexes with drugs further expands their potential in drug delivery systems. However, challenges such as bitterness, cytotoxicity, and instability under certain conditions need to be addressed for effective utilization of saponins in foods and related applications. In this paper, we have reviewed the chemistry, functionality, and application aspects of saponins from various plant sources, and have summarized the regulatory aspects of the food-based application of quillaja saponins. Further research to explore the full potential of saponins in improving food quality and human health has been suggested. It is expected that this article will be a useful resource for researchers in food, feed, pharmaceuticals, and material science.
Topics: Humans; Saponins; Food; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antiparasitic Agents
PubMed: 37686341
DOI: 10.3390/ijms241713538 -
Frontiers in Cellular and Infection... 2024Malaria has always been a serious infectious disease prevalent in the world. Antimalarial drugs such as chloroquine and artemisinin have been the main compounds used to... (Review)
Review
BACKGROUND
Malaria has always been a serious infectious disease prevalent in the world. Antimalarial drugs such as chloroquine and artemisinin have been the main compounds used to treat malaria. However, the massive use of this type of drugs accelerates the evolution and spread of malaria parasites, leading to the development of resistance. A large number of related data have been published by researchers in recent years. CiteSpace software has gained popularity among us researchers in recent years, because of its ability to help us obtain the core information we want in a mass of articles. In order to analyze the hotspots and develop trends in this field through visual analysis, this study used CiteSpace software to summarize the available data in the literature to provide insights.
METHOD
Relevant literature was collected from the Web of Science Core Collection (WOSCC) from 1 January 2015 to 29 March 2023. CiteSpace software and Microsoft Excel were used to analyze and present the data, respectively.
RESULTS
A total of 2,561 literatures were retrieved and 2,559 literatures were included in the analysis after the removal of duplicates. An irrefutable witness of the ever-growing interest in the topic of antimalarial drug resistance could be expressed by the exponentially increased number of publications and related citations from 2015 to 2022, and its sustained growth trend by 2023. During the past 7 years, USA, Oxford University, and David A Fidock are the country, institution, and author with the most publications in this field of research, respectively. We focused on the references and keywords from literature and found that the research and development of new drugs is the newest hotspot in this field. A growing number of scientists are devoted to finding new antimalarial drugs.
CONCLUSION
This study is the first visual metrological analysis of antimalarial drug resistance, using bibliometric methods. As a baseline information, it is important to analyze research output published globally on antimalarial drug resistance. In order to better understand the current research situation and future research plan agenda, such baseline data are needed accordingly.
Topics: Humans; Antimalarials; Chloroquine; Bibliometrics; Folic Acid Antagonists; Malaria
PubMed: 38410722
DOI: 10.3389/fcimb.2024.1270060 -
Annals of African Medicine 2024Malaria is a disease affecting millions of people, especially in Africa, Asia, and South America, and has become a substantial economic burden. Because malaria is... (Review)
Review
Malaria is a disease affecting millions of people, especially in Africa, Asia, and South America, and has become a substantial economic burden. Because malaria is contracted through the bite of a mosquito vector, it is very challenging to prevent. Bed nets and insect repellents are used in some homes; others do not have or use them even when available. Thus, treatment measures are crucial to controlling this disease. Artemisinin-based combination therapy (ACT) is currently the first-line treatment for malaria. ACT has been used for decades, but recently, there has been evidence of potential resistance. This threat of resistance has led to the search for possible alternatives to ACT. In sub-Saharan Africa, Azadirachta indica, or simply neem, is a plant used to treat a variety of ailments, including malaria. Neem is effective against one of the more deadly malaria parasites Plasmodium falciparum. Reports show that neem inhibits microgametogenesis of P. falciparum and interferes with the parasite's ookinete development. Although there is substantial in vitro research on the biological activity of A. indica (neem), there is limited in vivo research. Herein, we discuss the in vivo effects of neem on malaria parasites. With A. indica, the future of malaria treatment is promising, especially for high-risk patients, but further research and clinical trials are required to confirm its biological activity.
Topics: Animals; Humans; Plant Extracts; Malaria; Plasmodium falciparum; Africa South of the Sahara; Azadirachta; Antimalarials; Malaria, Falciparum
PubMed: 38358164
DOI: 10.4103/aam.aam_35_23 -
Parasitology Research Dec 2023The One-Health approach recognizes the intricate connection between human, animal, and environmental health, and that cooperative effort from various professionals... (Review)
Review
The One-Health approach recognizes the intricate connection between human, animal, and environmental health, and that cooperative effort from various professionals provides comprehensive awareness and potential solutions for issues relating to the health of people, animals, and the environment. This approach has increasingly gained appeal as the standard strategy for tackling emerging infectious diseases, most of which are zoonoses. Treatment with anthelmintics (AHs) without a doubt minimizes the severe consequences of soil-transmitted helminths (STHs); however, evidence of anthelmintic resistance (AR) development to different helminths of practically every animal species and the distinct groups of AHs is overwhelming globally. In this regard, the correlation between the application of anthelmintic drugs in both human and animal populations and the consequent development of anthelmintic resistance in STHs within the context of a One-Health framework is explored. This review provides an overview of the major human and animal STHs, treatment of the STHs, AR development and drug-related factors contributing towards AR, One-Health and STHs, and an outline of some One-Health strategies that may be used in combating AR.
Topics: Animals; Humans; Helminthiasis; Soil; One Health; Anthelmintics; Helminths
PubMed: 38114766
DOI: 10.1007/s00436-023-08088-8 -
Nature Communications Jul 2023Increasing levels of artemisinin and partner drug resistance threaten malaria control and elimination globally. Triple artemisinin-based combination therapies (TACTs)...
Increasing levels of artemisinin and partner drug resistance threaten malaria control and elimination globally. Triple artemisinin-based combination therapies (TACTs) which combine artemisinin derivatives with two partner drugs are efficacious and well tolerated in clinical trials, including in areas of multidrug-resistant malaria. Whether early TACT adoption could delay the emergence and spread of antimalarial drug resistance is a question of vital importance. Using two independent individual-based models of Plasmodium falciparum epidemiology and evolution, we evaluated whether introduction of either artesunate-mefloquine-piperaquine or artemether-lumefantrine-amodiaquine resulted in lower long-term artemisinin-resistance levels and treatment failure rates compared with continued ACT use. We show that introduction of TACTs could significantly delay the emergence and spread of artemisinin resistance and treatment failure, extending the useful therapeutic life of current antimalarial drugs, and improving the chances of malaria elimination. We conclude that immediate introduction of TACTs should be considered by policy makers in areas of emerging artemisinin resistance.
Topics: Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Artemisinins; Folic Acid Antagonists
PubMed: 37516752
DOI: 10.1038/s41467-023-39914-3 -
The New England Journal of Medicine Sep 2023Although the clinical efficacy of antimalarial artemisinin-based combination therapies in Africa remains high, the recent emergence of partial resistance to artemisinin...
BACKGROUND
Although the clinical efficacy of antimalarial artemisinin-based combination therapies in Africa remains high, the recent emergence of partial resistance to artemisinin in on the continent is troubling, given the lack of alternative treatments.
METHODS
In this study, we used data from drug-efficacy studies conducted between 2016 and 2019 that evaluated 3-day courses of artemisinin-based combination therapy (artesunate-amodiaquine or artemether-lumefantrine) for uncomplicated malaria in Eritrea to estimate the percentage of patients with day-3 positivity (i.e., persistent parasitemia 3 days after the initiation of therapy). We also assayed parasites for mutations in as predictive markers of partial resistance to artemisinin and screened for deletions in and that result in variable performance of histidine rich protein 2 (HRP2)-based rapid diagnostic tests for malaria.
RESULTS
We noted an increase in the percentage of patients with day-3 positivity from 0.4% (1 of 273) in 2016 to 1.9% (4 of 209) in 2017 and 4.2% (15 of 359) in 2019. An increase was also noted in the prevalence of the R622I mutation, which was detected in 109 of 818 isolates before treatment, from 8.6% (24 of 278) in 2016 to 21.0% (69 of 329) in 2019. The odds of day-3 positivity increased by a factor of 6.2 (95% confidence interval, 2.5 to 15.5) among the patients with 622I variant parasites. Partial resistance to artemisinin, as defined by the World Health Organization, was observed in Eritrea. More than 5% of the patients younger than 15 years of age with day-3 positivity also had parasites that carried R622I. In vitro, the R622I mutation conferred a low level of resistance to artemisinin when edited into NF54 and Dd2 parasite lines. Deletions in both and were identified in 16.9% of the parasites that carried the R622I mutation, which made them potentially undetectable by HRP2-based rapid diagnostic tests.
CONCLUSIONS
The emergence and spread of lineages with both -mediated partial resistance to artemisinin and deletions in and in Eritrea threaten to compromise regional malaria control and elimination campaigns. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry numbers, ACTRN12618001223224, ACTRN12618000353291, and ACTRN12619000859189.).
Topics: Humans; Amodiaquine; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Drug Resistance; Eritrea; Malaria, Falciparum; Plasmodium falciparum; Prevalence
PubMed: 37754284
DOI: 10.1056/NEJMoa2210956 -
Marine Drugs Nov 2023Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable... (Review)
Review
Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. Marine-derived cyclic peptides have been increasingly screened as candidates for developing new drugs. Therefore, in this review, a systematic analysis of the scientific literature was performed and 25 marine-derived cyclic peptides with antiparasitic activity (-) were found. Antimalarial activity is the most reported (51%), followed by antileishmanial (27%) and antitrypanosomal (20%) activities. Some compounds showed promising antiparasitic activity at the nM scale, being active against various parasites. The mechanisms of action and targets for some of the compounds have been investigated, revealing different strategies against parasites.
Topics: Humans; Antiparasitic Agents; Peptides, Cyclic; Leishmaniasis; Antiprotozoal Agents; Parasitic Diseases
PubMed: 38132930
DOI: 10.3390/md21120609