Progress in the research of artemisinin-related antimalarials: An update (original) (raw)
Related papers
Journal of Natural Medicines
Malaria is a worldwide disease caused by Plasmodium parasites. A sesquiterpene endoperoxide artemisinin isolated from Artemisia annua was discovered and has been accepted for its use in artemisinin-based combinatorial therapies, as the most effective current antimalarial treatment. However, the quantity of this compound produced from the A. annua plant is very low, and the availability of artemisinin is insufficient to treat all infected patients. In addition, the emergence of artemisinin-resistant Plasmodium has been reported recently. Several techniques have been applied to enhance artemisinin availability, and studies related to its mode of action and the mechanism of resistance of malaria-causing parasites are ongoing. In this review, we summarize the application of modern technologies to improve the production of artemisinin, including our ongoing research on artemisinin biosynthetic genes in other Artemisia species. The current understanding of the mode of action of artemisinin as well as the mechanism of resistance against this compound in Plasmodium parasites is also presented. Finally, the current situation of malaria infection and the future direction of antimalarial drug development are discussed.
Current status of artemisinin and its derivatives as antimalarial drugs
Life Sciences, 1999
Artemisinin is a promising and a potent antimalarial drug, which meets the dual challenge posed by drug-resistant parasites and rapid progression of malarial illness. This review article focuses on the progress achieved during the last years in the production of artemisinin from Artemisia annua. The structure, biosynthesis and analysis of artemisinin and its mode of action are described. The review also focuses on clinical studies, toxicity studies, pharmacokinetics and activity of artemisinin related compounds. The production strategies including organic synthesis, extraction from plants, in vitro cultures and alternative strategies for enhancing the yields are also discussed.
Artemisinin , a Potential Antimalarial Drug : Current Status
2016
Artemisinin, known as Qinghaosu in China, is one of the constituents of quinhao, a Traditional Chinese M dicine (TCM) and is known to possess antimalarial activity since centuries in China. Artemisinin constitutes the frontline treatment to aid rapid clearance of parasitaemia an d quick resolution of malarial symptoms. Combinatio n regimens that include artemisinin derivatives are recommende d as first line antimalarials in most countries whe re malaria is endemic. Artemisinin possessed an unique chemical s tructure with an inter-peroxyl ketal-acetal-lactone consisting of –OO-C-O-C-O-C=O segment. In the present review arti cle artemisinin as a potential antimalarial drug an d a lead molecule is discussed by including its chemistry, m echanism of action, artemisinin derivatives and str ucture-activity relationship (SAR) study, and commercial production of artemisinin.
Anais da Academia Brasileira de Ciencias, 2018
According to the World Health Organization, malaria remains one of the biggest public health problems in the world. The development of resistance is a current concern, mainly because the number of safe drugs for this disease is limited. Artemisinin-based combination therapy is recommended by the World Health Organization to prevent or delay the onset of resistance. Thus, the need to obtain new drugs makes artemisinin the most widely used scaffold to obtain synthetic compounds. This review describes the drugs based on artemisinin and its derivatives, including hybrid derivatives and dimers, trimers and tetramers that contain an endoperoxide bridge. This class of compounds is of extreme importance for the discovery of new drugs to treat malaria.
Traditional antimalarials and the development of novel antimalarial drugs
Journal of Ethnopharmacology, 2005
Malaria continues to be a major cause of mortality and morbidity especially throughout the developing world. In the last 25 years or so a number of significant advances have been made that have the potential to make a major contribution to the control of this disease. The discovery of artemisinin and its analogues as potent antimalarial agents have been of immense importance and the latter, as well as some other selected developments are outlined in this brief review.
Cogent Biology, 2018
The antimalarial active compounds in Artemisia annua include artemisinin, flavonoids, and aromatic oils. Artemisinin is the main antimalarial compound in A. annua, it used in the formulation of artemisinin-based combined therapies used to treat malaria. Artemisinin is largely obtained from A. annua plant but the content in it is very low and its production commercially is not cost effective worldwide. Flavonoids have a synergistic effect with artemisinin against malaria and are partly responsible for the prophylactic effect of A. annua herbal tea. Essential oils from A. annua are effective mosquito repellents. Most attempts have been made to try to raise artemisinin content. However, few or none has been tried to increase the flavonoids and aromatic oils. This article presents a review of various efforts that have been carried out to increase these antimalarial compounds.
PLOS ONE, 2021
Dried-leaf Artemisia annua L. (DLA) antimalarial therapy was shown effective in prior animal and human studies, but little is known about its mechanism of action. Here IC50s and ring-stage assays (RSAs) were used to compare extracts of A. annua (DLAe) to artemisinin (ART) and its derivatives in their ability to inhibit and kill Plasmodium falciparum strains 3D7, MRA1252, MRA1240, Cam3.11 and Cam3.11rev in vitro. Strains were sorbitol and Percoll synchronized to enrich for ring-stage parasites that were treated with hot water, methanol and dichloromethane extracts of DLA, artemisinin, CoArtem™, and dihydroartemisinin. Extracts of A. afra SEN were also tested. There was a correlation between ART concentration and inhibition of parasite growth. Although at 6 hr drug incubation, the RSAs for Cam3.11rev showed DLA and ART were less effective than high dose CoArtem™, 8 and 24 hr incubations yielded equivalent antiparasitic results. For Cam3.11, drug incubation time had no effect. DLAe was...
Cogent biology, 2018
The antimalarial active compounds in Artemisia annua include artemisinin, flavonoids, and aromatic oils. Artemisinin is the main antimalarial compound in A. annua, it used in the formulation of artemisinin-based combined therapies used to treat malaria. Artemisinin is largely obtained from A. annua plant but the content in it is very low and its production commercially is not cost effective worldwide. Flavonoids have a synergistic effect with artemisinin against malaria and are partly responsible for the prophylactic effect of A. annua herbal tea. Essential oils from A. annua are effective mosquito repellents. Most attempts have been made to try to raise artemisinin content. However, few or none has been tried to increase the flavonoids and aromatic oils. This article presents a review of various efforts that have been carried out to increase these antimalarial compounds.
In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative
Medicines
Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against Plasmodium falciparum malaria, but parasite resistance to artemisinin (ART) and its derivatives, core components of ACTs, is spreading in the Mekong countries. In this study, we report the synthesis of several novel artemisinin derivatives and evaluate their in vitro and in silico capacity to counteract Plasmodium falciparum artemisinin resistance. Furthermore, recognizing that the malaria parasite devotes considerable resources to minimizing the oxidative stress that it creates during its rapid consumption of hemoglobin and the release of heme, we sought to explore whether further augmentation of this oxidative toxicity might constitute an important addition to artemisinins. The present report demonstrates, in vitro, that FM-AZ, a newly synthesized artemisinin derivative, has a lower IC50 than artemisinin in P. falciparum and a rapid action in killing the parasites. The docking studies for ...
Aromatic amino analogues of artemisinin: synthesis and in vivo antimalarial activity
Medicinal Chemistry Research, 2010
Nine orally active novel artemisinin derivatives were prepared from artemisinin by four-step synthesis, and the compounds were evaluated in the rodent model using multidrug resistant Plasmodium yoelii nigeriensis. All of the compounds exhibited antimalarial activities with the ED 50 ranging from 5.41 mg/kg-12.4 mg/kg. Among them, artemisinin derivative bearing N-(4-hydroxy-3-((4-phenylpiperazin-1-yl)methyl)phenyl) moiety (5f) was found to be the most active compound and was found to be three times more potent than artemisinin (ED 50 16.4 mg/kg).