According to WHO World Malaria Report (2018), nearly 219 million new cases of malaria occurred and a total no. of 435 000 people died in 2017 due to this infectious disease. This is due to the rapid spread of parasite-resistant strains. Artemisinin (ART), a sesquiterpene lactone endoperoxide isolated from traditional Chinese herb Artemisia annua, has been recognized as a novel class of antimalarial drugs. The 2015 "Nobel Prize in Physiology or Medicine" was given to Prof Dr Tu Youyou for the discovery of ART. Hence, ART is termed as "Nobel medicine." The present review article accommodates insights from the chronological advancements and direct statistics witnessed during the past 48 years (1971-2019) in the medicinal chemistry of ART-derived antimalarial endoperoxides, and their clinical utility in malaria chemotherapy and drug discovery.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/med.21657 | DOI Listing |
Parasitol Int
December 2024
Division of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. Electronic address:
Through studies of new antimalarial drugs, we identified 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) as a potential drug candidate. Here, we analyzed the antimalarial action of a transdermal formulation (td) of N-89, designed for easy use by children, using Plasmodium berghei-infected mice as a model for malaria patients.
View Article and Find Full Text PDFACS Infect Dis
January 2025
Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 4, France.
The 1,2,4-trioxolane antimalarial drug, OZ439 (artefenomel), exhibits cross-resistance to artemisinins with similar survival rates of artemisinin-resistant parasites after dihydroartemisinin or OZ439 exposure, suggesting that this drug shares some mechanisms of action with artemisinins. In this way, we investigated the reductive activation of OZ439 by heme in the presence of dithionite, demonstrating the formation of covalent heme-drug adducts. However, in the presence of the biologically abundant reductant glutathione instead of dithionite, heme-drug adducts were not detected, contrary to artemisinin that efficiently alkylates heme regardless of the reductant used.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China; The Second Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou 510260, China. Electronic address:
Artemisitene (ATT), an artemisinin (ART) analog retaining the endoperoxide moiety and incorporating an additional α, β-unsaturated carbonyl structure, exhibits enhanced biological activities. However, its therapeutic effects on liver fibrosis remain unclear. In this study, we demonstrated that ATT significantly alleviated liver inflammation and fibrosis induced by carbon tetrachloride (CCL) in mice.
View Article and Find Full Text PDFCommun Biol
November 2024
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, Delhi, 110067, India.
The potency of frontline antimalarial drug artemisinin (ART) derivatives is triggered by heme-induced cleavage of the endoperoxide bond to form reactive heme-ART alkoxy radicals and covalent heme-ART adducts, which are highly toxic to the parasite. ART-resistant (ART-R) parasites with mutations in the Plasmodium falciparum Kelch-containing protein Kelch13 (PfKekch13) exhibit impaired hemoglobin uptake, reduced yield of hemoglobin-derived heme, and thus decreased ART activation. However, any direct involvement of PfKelch13 in heme-mediated ART activation has not been reported.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Department of Chemistry, Banasthali University, Banasthali Newai, 304022, Rajasthan, India; Department of Education in Science and Mathematics (DESM), Regional Institute of Education (NCERT), Bhubaneshwar, 751022, India. Electronic address:
Malaria pertains to an array of catastrophic illnesses spurred on by the Plasmodium spp. Artemisinin (ART) is currently prescribed in conjunction with another medication as part of therapeutic regimens for acute malaria. These currently prescribed pharmaceuticals have been around for a while, even after lack of required thermos-metabolic stabilities, alongside fresh proclaims about surfacing resistance and neurotoxicity linked with sequential administration of such combination therapies.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!