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Drug Design, Development and Therapy 2023Malaria remains to be a national and global challenge and priority, as stated in the strategic plan of the Indonesian Ministry of Health and Sustainable Development... (Review)
Review
Malaria remains to be a national and global challenge and priority, as stated in the strategic plan of the Indonesian Ministry of Health and Sustainable Development Goals. In Indonesia, it is targeted that malaria elimination can be achieved by 2030. Unfortunately, the development and spread of antimalarial resistance inflicts a significant risk to the national malaria control programs which can lead to increased malaria morbidity and mortality. In Indonesia, resistance to widely used antimalarial drugs has been reported in two human species, and . With the exception of artemisinin, resistance has surfaced towards all classes of antimalarial drugs. Initially, chloroquine, sulfadoxine-pyrimethamine, and primaquine were the most widely used antimalarial drugs. Regrettably, improper use has supported the robust spread of their resistance. Chloroquine resistance was first reported in 1974, while sulfadoxine-pyrimethamine emerged in 1979. Twenty years later, most provinces had declared treatment failures of both drugs. Molecular epidemiology suggested that variations in and genes were associated with chloroquine resistance, while and genes were correlated with sulfadoxine-pyrimethamine resistance. Additionally, and of genes appeared to be early warning sign to artemisinin resistance. Here, we reported mechanisms of antimalarial drugs and their development of resistance. This insight could provide awareness toward designing future treatment guidelines and control programs in Indonesia.
Topics: Humans; Antimalarials; Indonesia; Chloroquine; Artemisinins
PubMed: 37431492
DOI: 10.2147/DDDT.S403672 -
Malaria Journal Nov 2014Primaquine is the only generally available anti-malarial that prevents relapse in vivax and ovale malaria, and the only potent gametocytocide in falciparum malaria.... (Review)
Review
Primaquine is the only generally available anti-malarial that prevents relapse in vivax and ovale malaria, and the only potent gametocytocide in falciparum malaria. Primaquine becomes increasingly important as malaria-endemic countries move towards elimination, and although it is widely recommended, it is commonly not given to malaria patients because of haemolytic toxicity in subjects who are glucose-6-phosphate dehydrogenase (G6PD) deficient (gene frequency typically 3-30% in malaria endemic areas; >180 different genetic variants). In six decades of primaquine use in approximately 200 million people, 14 deaths have been reported. Confining the estimate to reports with known denominators gives an estimated mortality of one in 621,428 (upper 95% CI: one in 407,807). All but one death followed multiple dosing to prevent vivax malaria relapse. Review of dose-response relationships and clinical trials of primaquine in G6PD deficiency suggests that the currently recommended WHO single low dose (0.25 mg base/kg) to block falciparum malaria transmission confers a very low risk of haemolytic toxicity.
Topics: Antimalarials; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Malaria, Falciparum; Primaquine
PubMed: 25363455
DOI: 10.1186/1475-2875-13-418 -
Journal of Natural Medicines Jan 2022Eight new limonoids, walsogynes H-O (1-8) were isolated from the barks of Walsura chrysogyne, and their structures were determined on the basis of the 1D and 2D NMR...
Eight new limonoids, walsogynes H-O (1-8) were isolated from the barks of Walsura chrysogyne, and their structures were determined on the basis of the 1D and 2D NMR data. Walsogynes H-M (1-6) and O (8) were concluded to be 11,12-seco limonoids with a dodecahydro-1H-naphtho[1,8-bc:3,4-c']difuran skeleton, and walsogyne N (7) to be 11,12-seco limonoid sharing a unique dodecahydronaphtho[1,8-bc:5,4-b'c']difuran skeleton. Walsogynes H-O (1-8) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC value of 2.5, 2.6, 1.6, 2.5, 1.5, 2.6, 2.1, and 1.1 µM, respectively.
Topics: Antimalarials; Limonins; Magnetic Resonance Spectroscopy; Meliaceae; Molecular Structure; Plasmodium falciparum
PubMed: 34351584
DOI: 10.1007/s11418-021-01556-4 -
Malaria Journal Jun 2022
Topics: Antimalarials; Checklist; Folic Acid Antagonists; Research Design
PubMed: 35698123
DOI: 10.1186/s12936-022-04182-x -
Antimicrobial Agents and Chemotherapy Feb 2022The emergence and spread of parasite resistance to currently available antimalarials has highlighted the importance of developing novel antimalarials. This scoping... (Review)
Review
The emergence and spread of parasite resistance to currently available antimalarials has highlighted the importance of developing novel antimalarials. This scoping review provides an overview of antimalarial drug candidates undergoing phase I and II studies between 1 January 2016 and 28 April 2021. PubMed, Web of Science, Embase, clinical trial registries, and reference lists were searched for relevant studies. Information regarding antimalarial compound details, clinical trial characteristics, study population, and drug pharmacokinetics and pharmacodynamics (PK-PD) were extracted. A total of 50 studies were included, of which 24 had published their results and 26 were unpublished. New antimalarial compounds were evaluated as monotherapy (28 studies, 14 drug candidates) and combination therapy (9 studies, 10 candidates). Fourteen active compounds were identified in the current antimalarial drug development pipeline together with 11 compounds that are inactive, 6 due to insufficient efficacy. PK-PD data were available from 24 studies published as open-access articles. Four unpublished studies have made their results publicly available on clinical trial registries. The terminal elimination half-life of new antimalarial compounds ranged from 14.7 to 483 h. The log parasite reduction ratio over 48 h and parasite clearance half-life for Plasmodium falciparum following a single-dose monotherapy were 1.55 to 4.1 and 3.4 to 9.4 h, respectively. The antimalarial drug development landscape has seen a number of novel compounds, with promising PK-PD properties, evaluated in phase I and II studies over the past 5 years. Timely public disclosure of PK-PD data is crucial for informative decision-making and drug development strategy.
Topics: Antimalarials; Drug Development; Drug Resistance; Humans; Malaria, Falciparum; Plasmodium falciparum
PubMed: 34843390
DOI: 10.1128/AAC.01659-21 -
Malaria Journal Feb 2016Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to... (Review)
Review
Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination.
Topics: Angola; Antimalarials; Drug Resistance; Humans; Malaria, Falciparum; Plasmodium falciparum
PubMed: 26858018
DOI: 10.1186/s12936-016-1122-z -
Revista Espanola de Quimioterapia :... Sep 2016Malaria is one of the most widespread infectious diseases around the world with 214 million cases and 438,000 deaths in 2015. In the early twentieth century it was... (Review)
Review
Malaria is one of the most widespread infectious diseases around the world with 214 million cases and 438,000 deaths in 2015. In the early twentieth century it was described for the first time the resistance to quinine and, since then, drug resistance to antimalarial drugs has spread up to represent a global challenge in the fight and control of malaria. Understanding the mechanisms, geography and monitoring tools that we can act against resistance to antimalarial drugs is critical to prevent its expansion.
Topics: Antimalarials; Drug Resistance; Humans; Malaria; Plasmodium; Quinine
PubMed: 27608319
DOI: No ID Found -
The Lancet. Infectious Diseases Apr 2018Over the past 10 years, the available evidence on the treatment of malaria during pregnancy has increased substantially. Owing to their relative ease of use, good... (Review)
Review
Over the past 10 years, the available evidence on the treatment of malaria during pregnancy has increased substantially. Owing to their relative ease of use, good sensitivity and specificity, histidine rich protein 2 based rapid diagnostic tests are appropriate for symptomatic pregnant women; however, such tests are less appropriate for systematic screening because they will not detect an important proportion of infections among asymptomatic women. The effect of pregnancy on the pharmacokinetics of antimalarial drugs varies greatly between studies and class of antimalarial drugs, emphasising the need for prospective studies in pregnant and non-pregnant women. For the treatment of malaria during the first trimester, international guidelines are being reviewed by WHO. For the second and third trimester of pregnancy, results from several trials have confirmed that artemisinin-based combination treatments are safe and efficacious, although tolerability and efficacy might vary by treatment. It is now essential to translate such evidence into policies and clinical practice that benefit pregnant women in countries where malaria is endemic. Access to parasitological diagnosis or appropriate antimalarial treatment remains low in many countries and regions. Therefore, there is a pressing need for research to identify quality improvement interventions targeting pregnant women and health providers. In addition, efficient and practical systems for pharmacovigilance are needed to further expand knowledge on the safety of antimalarial drugs, particularly in the first trimester of pregnancy.
Topics: Antimalarials; Artemisinins; Diagnostic Tests, Routine; Female; Global Health; Humans; Lactones; Malaria; Pharmacovigilance; Pregnancy; Pregnancy Complications, Infectious
PubMed: 29395998
DOI: 10.1016/S1473-3099(18)30065-3 -
Drug Research Jan 2021Drug repositioning is a strategy that identifies new uses of approved drugs to treat conditions different from their original purpose. Current efforts to treat Covid-19...
Drug repositioning is a strategy that identifies new uses of approved drugs to treat conditions different from their original purpose. Current efforts to treat Covid-19 are based on this strategy. The first drugs used in patients infected with SARS-CoV-2 were antimalarial drugs. It is their mechanism of action, i. e., rise in endosomal pH, which recommends them against the new coronavirus. Disregarding their side effects, the study of their antiviral activity provides valuable hints for the choice and design of drugs against SARS-CoV-2. One prominent drug candidate is thymoquinone, an antimalarial substance contained in Nigella sativa - most likely one of the first antimalarial drugs in human history. Since the outbreak of the pandemic, the number of articles relating thymoquinone to Covid-19 continuously increases. Here, we use it as an exemplary model drug, compare its antiviral mechanism with that of conventional antimalarial drugs and establish an irreducible parametric scheme for the identification of drugs with a potential in Covid-19.Translation into the laboratory is simple. Starting with the discovery of Nigella sativa seeds in the tomb of Pharaoh Tutankhamun, we establish a physicochemical model for the interaction of thymoquinone with both coronavirus and cells. Exploiting the predictive capability of the model, we provide a generalizable scheme for the systematic choice and design of drugs for Covid-19. An unexpected offshoot of our research is that Tutankhamun could not have died of malaria, a finding contrary to the mainstream theory.
Topics: Antimalarials; Antiviral Agents; Benzoquinones; Drug Repositioning; Egypt; Famous Persons; History, Ancient; Humans; Nigella sativa; COVID-19 Drug Treatment
PubMed: 33128226
DOI: 10.1055/a-1274-1264 -
Molecules (Basel, Switzerland) Dec 2022Bioassay-guided fractionation technique of roots of led to isolation and structure elucidation of seven known compounds, including four monoterpene glycosides:...
Bioassay-guided fractionation technique of roots of led to isolation and structure elucidation of seven known compounds, including four monoterpene glycosides: lactiflorin (), paeoniflorin (), galloyl paeoniflorin (), and ()-(1,5)--pinen-10-yl -vicianoside (); two phenolics: benzoic acid () and methyl gallate (); and one sterol glycoside: -sitosterol 3---D-glucopyranoside (). The different fractions and the isolated compounds were evaluated for their antimicrobial and antimalarial activities. Fraction II and III showed antifungal activity against with IC values of 28.11 and 74.37 µg/mL, respectively, compared with the standard fluconazole (IC = 4.68 µg/mL), and antibacterial potential against (IC = 20.27 and 24.82 µg/mL, respectively) and (IC = 43.21 and 94.4 µg/mL, respectively), compared with the standard meropenem (IC = 28.67 and 43.94 µg/mL, respectively). Compounds and showed antimalarial activity against D6 with IC values of 1.57 and 4.72 µg/mL and W2 with IC values of 0.61 and 2.91 µg/mL, respectively, compared with the standard chloroquine (IC = 0.026 and 0.14 µg/mL, respectively).
Topics: Antimalarials; Paeonia; Plasmodium falciparum; Chemical Fractionation; Anti-Infective Agents; Plant Extracts
PubMed: 36500473
DOI: 10.3390/molecules27238382