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Pharmacology & Therapeutics Dec 2020As the first-line antimalarial drugs, artemisinins gained wide acceptance after the emergence of resistance to chloroquine in the 1950s. Artemisinin-based drugs have... (Review)
Review
As the first-line antimalarial drugs, artemisinins gained wide acceptance after the emergence of resistance to chloroquine in the 1950s. Artemisinin-based drugs have saved lives, especially in developing countries. The discovery of artemisinin was unique, timely, and fascinating, and the benefits of artemisinin were with far-reaching implications. Herein, we will give a brief description of various aspects of the development of artemisinin and discuss the position and perspectives of artemisinin-based drugs.
Topics: Animals; Antimalarials; Artemisia annua; Artemisinins; Humans; Malaria; Molecular Structure; Plasmodium; Structure-Activity Relationship
PubMed: 32777330
DOI: 10.1016/j.pharmthera.2020.107658 -
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 -
Progress in the Chemistry of Organic... 2022Natural products have made a crucial and unique contribution to human health, and this is especially true in the case of malaria, where the natural products quinine and...
Natural products have made a crucial and unique contribution to human health, and this is especially true in the case of malaria, where the natural products quinine and artemisinin and their derivatives and analogues, have saved millions of lives. The need for new drugs to treat malaria is still urgent, since the most dangerous malaria parasite, Plasmodium falciparum, has become resistant to quinine and most of its derivatives and is becoming resistant to artemisinin and its derivatives. This volume begins with a short history of malaria and follows this with a summary of its biology. It then traces the fascinating history of the discovery of quinine for malaria treatment and then describes quinine's biosynthesis, its mechanism of action, and its clinical use, concluding with a discussion of synthetic antimalarial agents based on quinine's structure. The volume then covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of other natural products with significant antiplasmodial activity, classified by compound type. Although the search for new antimalarial natural products from Nature's combinatorial library is challenging, it is very likely to yield new antimalarial drugs. The chapter thus ends by identifying over ten natural products with development potential as clinical antimalarial agents.
Topics: Antimalarials; Biological Products; Humans; Malaria; Plasmodium falciparum; Quinine
PubMed: 34977998
DOI: 10.1007/978-3-030-89873-1_1 -
Molecules (Basel, Switzerland) Oct 2019Malaria and cancer are chronic diseases. The challenge with drugs available for the treatment of these diseases is drug toxicity and resistance. Ferrocene is a potent... (Review)
Review
Malaria and cancer are chronic diseases. The challenge with drugs available for the treatment of these diseases is drug toxicity and resistance. Ferrocene is a potent organometallic which have been hybridized with other compounds resulting in compounds with enhanced biological activity such as antimalarial and anticancer. Drugs such as ferroquine were developed from ferrocene and chloroquine. It was tested in the 1990s as an antimalarial and is still an effective antimalarial. Many researchers have reported ferrocene compounds as potent compounds useful as anticancer and antimalarial agents when hybridized with other pharmaceutical scaffolds. This review will be focused on compounds with ferrocene moieties that exhibit either an anticancer or antimalarial activity.
Topics: Aminoquinolines; Antimalarials; Antineoplastic Agents; Chloroquine; Drug Resistance, Neoplasm; Drug Therapy, Combination; Ferrous Compounds; Humans; Malaria; Metallocenes; Neoplasms; Plasmodium falciparum
PubMed: 31591298
DOI: 10.3390/molecules24193604 -
Current Opinion in Pharmacology Oct 2018Over the past decade, new high-throughput phenotypic assays with malaria parasites have been developed, and these were used to screen millions of compounds. This effort,... (Review)
Review
Over the past decade, new high-throughput phenotypic assays with malaria parasites have been developed, and these were used to screen millions of compounds. This effort, as well as improving older chemical scaffolds and optimising compounds against both known and new drug targets has resulted in the discovery of exciting new pipeline drug candidates that are now being evaluated in a number of clinical trials. In addition, the pitfalls and opportunities from this experience has led to a better definition of the optimal target compound and product profiles for new antimalarials, including medicines that treat uncomplicated or severe malaria, provide chemoprevention, or stop disease transmission, covering all stages of the parasite. An important decision element is how to combine these new molecules with existing ones in today's dynamic resistance landscape.
Topics: Animals; Antimalarials; Drug Discovery; Humans; Malaria
PubMed: 29860174
DOI: 10.1016/j.coph.2018.05.006 -
Archiv Der Pharmazie Apr 2020Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge... (Review)
Review
Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug-resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Many chalcone derivatives demonstrate potential in vitro and in vivo antimalarial activity, so chalcone could be a useful template for the development of novel antimalarial agents. This review covers the recent development of chalcone hybrids as antimalarial agents. The critical aspects of the design and structure-activity relationship of these compounds are also discussed.
Topics: Animals; Antimalarials; Chalcone; Chemistry, Pharmaceutical; Drug Resistance; Humans; Malaria; Parasitic Sensitivity Tests; Plasmodium; Structure-Activity Relationship
PubMed: 32003489
DOI: 10.1002/ardp.201900350 -
Medecine Et Sante Tropicales Feb 2019There is currently a hazardous debate between the rational use of antimalarial drugs based on artemisinin derivatives and the antimalarial efficacy of plant extracts of...
There is currently a hazardous debate between the rational use of antimalarial drugs based on artemisinin derivatives and the antimalarial efficacy of plant extracts of Artemisia spp. This article recall some fundamental rules guiding progresses in malaria treatment and use of artemisinin, with the aim to provide discussion elements to identify the safest place responding to health situations for drugs and phytotherapy.
Topics: Antimalarials; Artemisia annua; Health Services Accessibility; Humans; Plant Preparations; Plants, Medicinal
PubMed: 31031254
DOI: 10.1684/mst.2019.0868 -
European Journal of Medicinal Chemistry Mar 2019Malaria, caused by protozoan parasites of the genus Plasmodium especially by the most prevalent parasite Plasmodium falciparum, represents one of the most devastating... (Review)
Review
Malaria, caused by protozoan parasites of the genus Plasmodium especially by the most prevalent parasite Plasmodium falciparum, represents one of the most devastating and common infectious disease globally. Nearly half of the world population is under the risk of being infected, and more than 200 million new clinical cases with around half a million deaths occur annually. Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance, so it's imperative to develop new antimalarials with great potency against both drug-susceptible and drug-resistant malaria. Triazoles, bearing a five-membered heterocyclic ring with three nitrogen atoms, exhibit promising in vitro antiplasmodial and in vivo antimalarial activities. Moreover, several triazole-based drugs have already used in clinics for the treatment of various diseases, demonstrating the excellent pharmaceutical profiles. Therefore, triazole derivatives have the potential for clinical deployment in the control and eradication of malaria. This review covers the recent advances of triazole derivatives especially triazole hybrids as potential antimalarials. The structure-activity relationship is also discussed to provide an insight for rational designs of more efficient antimalarial candidates.
Topics: Animals; Antimalarials; Humans; Parasitic Sensitivity Tests; Plasmodium; Triazoles
PubMed: 30711831
DOI: 10.1016/j.ejmech.2019.01.047 -
European Journal of Medicinal Chemistry Jan 2021Atovaquone belongs to a naphthoquinone class of drugs and is used in combination with proguanil (Malarone) for the treatment of acute, uncomplicated malaria caused by... (Review)
Review
Atovaquone belongs to a naphthoquinone class of drugs and is used in combination with proguanil (Malarone) for the treatment of acute, uncomplicated malaria caused by Plasmodium falciparum (including chloroquine-resistant P. falciparum/P. vivax). Numerous quinone-derived compounds have attracted considerable attention in the last few decades due to their potential in antimalarial drug discovery. Several semi-synthetic derivatives of natural quinones, synthetic quinones (naphtho-/benzo-quinone, anthraquinones, thiazinoquinones), and quinone-based hybrids were explored for their in vitro and in vivo antimalarial activities. A careful literature survey revealed that this topic has not been compiled as a review article so far. Therefore, we herein summarise the recent discovery (the year 2009-2020) of quinone based antimalarial compounds in chronological order. This compilation would be very useful towards the exploration of novel quinone-derived compounds against malarial parasites with promising efficacy and lesser side effects.
Topics: Antimalarials; Dose-Response Relationship, Drug; Malaria, Falciparum; Molecular Structure; Parasitic Sensitivity Tests; Plasmodium falciparum; Quinones; Structure-Activity Relationship
PubMed: 33333397
DOI: 10.1016/j.ejmech.2020.113084 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Apr 2023Malaria remains a major global public health concern, and nearly half of the global populations are still at risk of malaria infection. However, continuous emergence and... (Review)
Review
Malaria remains a major global public health concern, and nearly half of the global populations are still at risk of malaria infection. However, continuous emergence and spread of drug-resistant malaria parasite strains lead to ineffectiveness of conventional antimalarials. Therefore, development of novel antimalarial agents is of urgent need for malaria elimination. As an important component of the host natural immune defense system, antibacterial peptides provide the first line of defense against pathogenic invasion, and the mechanism of preferentially attacking the cell membrane makes them difficult to develop drug resistance. Antimicrobial peptides are therefore considered as a promising candidate for novel antimalarial agents. This review summarizes the advances in researches on antimicrobial peptides with antimalarial actions and discusses the potential of antimalarial peptides as novel antimalarials.
Topics: Humans; Antimalarials; Plasmodium; Malaria; Peptides; Drug Resistance; Antimicrobial Peptides; Plasmodium falciparum
PubMed: 37253570
DOI: 10.16250/j.32.1374.2023011