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Articles de revues sur le sujet « Antimalarial drug efficacy »

Auteur : Grafiati

Publié le 4 juin 2021

Mis à jour le 12 février 2022

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1

Ringwald, P. "Monitoring Antimalarial Drug Efficacy." Clinical Infectious Diseases 38, no. 8 (2004): 1192–93. http://dx.doi.org/10.1086/383152.

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Sá, Juliana M., Jason L. Chong, and Thomas E. Wellems. "Malaria drug resistance: new observations and developments." Essays in Biochemistry 51 (October 24, 2011): 137–60. http://dx.doi.org/10.1042/bse0510137.

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Drug-resistant micro-organisms became widespread in the 20th Century, often with devastating consequences, in response to widespread use of natural and synthetic drugs against infectious diseases. Antimalarial resistance provides one of the earliest examples, following the introduction of new medicines that filled important needs for prophylaxis and treatment around the globe. In the present chapter, we offer a brief synopsis of major antimalarial developments from two natural remedies, the qinghaosu and cinchona bark infusions, and of synthetic drugs inspired by the active components of these

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Tang, Yu-Qing, Qian Ye, He Huang, and Wei-Yi Zheng. "An Overview of Available Antimalarials: Discovery, Mode of Action and Drug Resistance." Current Molecular Medicine 20, no. 8 (2020): 583–92. http://dx.doi.org/10.2174/1566524020666200207123253.

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: Malaria is one of the three most deadly infectious diseases in the world and seriously endangers human health and life. To reduce the public health burden of this disease, scientists have focused on the discovery and development of effective antimalarial drugs, from quinine and chloroquine to antifolates and artemisinin and its derivatives, which all play a profound role in the treatment of malaria. However, drugresistant strains of Plasmodium falciparum have emerged due to frequent use of antimalarials and have become increasingly resistant to existing antimalarial drugs, causing disastrous

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White, Nicholas J. "The assessment of antimalarial drug efficacy." Trends in Parasitology 18, no. 10 (2002): 458–64. http://dx.doi.org/10.1016/s1471-4922(02)02373-5.

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Ujuamala Uloma Ezeani, Penaere Theresa Osahon, and Michael Chukwudi Ezeani. "Pattern of anti-malarial drugs and artemether combination therapy adherence in an institution based medical centre, Nigeria." World Journal of Advanced Research and Reviews 8, no. 3 (2020): 162–70. http://dx.doi.org/10.30574/wjarr.2020.8.3.0437.

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The change in policy guidelines for treating uncomplicated malaria became necessary because the therapeutic efficacy of chloroquine and SP had deteriorated. Hence compliance is a necessity to enable effective check on malaria. This work was carried out to evaluate antimalaria drug prescription and to update its usage in line with WHO guideline on Artemeter Combination therapy in a university based medical center. We utilized descriptive, cross-sectional, retrospective study of antimalaria prescriptions purposely carried out among male and female outpatients with mean age of 22.4±2.8 at a Unive

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MWANGI, JONATHAN M., and LISA C. RANFORD-CARTWRIGHT. "Genetic and genomic approaches for the discovery of parasite genes involved in antimalarial drug resistance." Parasitology 140, no. 12 (2013): 1455–67. http://dx.doi.org/10.1017/s0031182013000954.

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SUMMARYThe biggest threat to the war on malaria is the continued evolution of drug resistance by the parasite. Resistance to almost all currently available antimalarials now exists inPlasmodium falciparumwhich causes the most suffering among all human malaria parasites. Monitoring of antimalarial efficacy and the development and subsequent spread of resistance has become an important part in the treatment and control of malaria. With recent reports of reduced efficacy of artemisinin, the current recommended treatment for uncomplicated malaria, there is urgent need for better methods to recogni

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Bennett, Tyler N., Michelle Paguio, Bojana Gligorijevic, et al. "Novel, Rapid, and Inexpensive Cell-Based Quantification of Antimalarial Drug Efficacy." Antimicrobial Agents and Chemotherapy 48, no. 5 (2004): 1807–10. http://dx.doi.org/10.1128/aac.48.5.1807-1810.2004.

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ABSTRACT We report on the development of a new SYBR Green I-based plate assay for analyzing the activities of antimalarial drugs against intraerythrocytic Plasmodium falciparum. This assay is considerably faster, less labor-intensive, and less expensive than conventional radiotracer (e.g., [3H]hypoxanthine and [3H]ethanolamine)-based assays or P. falciparum lactate dehydrogenase activity-based assays. The assay significantly improves the pace at which antimalarial drug discovery efforts may proceed.

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Sunitha G N, Satyavati Dulipala D, and Girish Gudi. "Evaluation of metabolic stability of antimalarial and antiretroviral drugs." International Journal of Research in Pharmaceutical Sciences 10, no. 3 (2019): 2591–601. http://dx.doi.org/10.26452/ijrps.v10i3.1515.

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The concomitant administration of drugs and antimalarial drugs is recommended for the treatment of HIV (Human Immunodeficiency Virus) patients with malaria resulting in drug-drug interactions (DDI) causing either lack of efficacy or toxicities. Drug metabolism is often the first step in understanding the DDI potential of either a new chemical entity or a combination of drugs. inhibitor (PI) such as is a potent CYP 3A4 inhibitor and may interact with these antimalarial drugs that are metabolized by CYP3A4 to cause metabolism-related DDI's. the present study is an attempt to evaluate the potenti

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Dow, G. S., T. N. Heady, A. K. Bhattacharjee, et al. "Utility of Alkylaminoquinolinyl Methanols as New Antimalarial Drugs." Antimicrobial Agents and Chemotherapy 50, no. 12 (2006): 4132–43. http://dx.doi.org/10.1128/aac.00631-06.

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ABSTRACT Mefloquine has been one of the more valuable antimalarial drugs but has never reached its full clinical potential due to concerns about its neurologic side effects, its greater expense than that of other antimalarials, and the emergence of resistance. The commercial development of mefloquine superseded that of another quinolinyl methanol, WR030090, which was used as an experimental antimalarial drug by the U.S. Army in the 1970s. We evaluated a series of related 2-phenyl-substituted alkylaminoquinolinyl methanols (AAQMs) for their potential as mefloquine replacement drugs based on a s

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Fidock, David A., Philip J. Rosenthal, Simon L. Croft, Reto Brun, and Solomon Nwaka. "Antimalarial drug discovery: efficacy models for compound screening." Nature Reviews Drug Discovery 3, no. 6 (2004): 509–20. http://dx.doi.org/10.1038/nrd1416.

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Lentini, Giovanni, Maria Maddalena Cavalluzzi, and Solomon Habtemariam. "COVID-19, Chloroquine Repurposing, and Cardiac Safety Concern: Chirality Might Help." Molecules 25, no. 8 (2020): 1834. http://dx.doi.org/10.3390/molecules25081834.

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The desperate need to find drugs for COVID-19 has indicated repurposing strategies as our quickest way to obtain efficacious medicines. One of the options under investigation is the old antimalarial drug, chloroquine, and its analog, hydroxychloroquine. Developed as synthetic succedanea of cinchona alkaloids, these chiral antimalarials are currently in use as the racemate. Besides the ethical concern related to accelerated large-scale clinical trials of drugs with unproven efficacy, the known potential detrimental cardiac effects of these drugs should also be considered. In principle, the safe

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Tobón-Castaño, Alberto, Luisa Garcés-Murillo, Alexandra Ríos-Orrego, et al. "Artemeter-Lumefantrine therapeutic efficacy, safety and plasma levels in patients with uncomplicated falciparum malaria from the Colombian Pacific región." Infectio 22, no. 4 (2018): 199. http://dx.doi.org/10.22354/in.v22i4.738.

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Introduction: In Colombia, the published studies for the treatment of uncomplicated Plasmodium falciparum malaria with Artemether-Lumefantrine are scarce. The aim of the study was to evaluate the therapeutic efficacy and safety profile of this combination.Methods: A clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28-day World Health Organization validated protocol. Patients received supervised antimalarial treatment and the primary efficacy endpoint was the clinical and parasitological response. Safety was assessed through adverse events surveillance a

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Kalita, Jahnabi, Dipak Chetia, and Mithun Rudrapal. "Design, Synthesis, Antimalarial Activity and Docking Study of 7-Chloro-4- (2-(substituted benzylidene)hydrazineyl)quinolines." Medicinal Chemistry 16, no. 7 (2020): 928–37. http://dx.doi.org/10.2174/1573406415666190806154722.

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Background: Malaria is a growing infectious disease burden due to the increasing emergence of resistant strains of Plasmodium falciparum. Because of the limited therapeutic efficacy of available antimalarial drugs, the development of potent antimalarial drug agents is therefore an urgent requirement to fight against resistant malaria. Objective: The objective of this work was to develop novel quinoline-baed antimalarial agents that would be active against resistant P. falciparum malaria. Methods: Some 7-chloro-4-(2-(substituted benzylidene)hydrazineyl)quinolines were synthesized for the evalua

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Dembele, Laurent, Yaw Aniweh, Nouhoum Diallo, et al. "Plasmodium malariae and Plasmodium falciparum comparative susceptibility to antimalarial drugs in Mali." Journal of Antimicrobial Chemotherapy 76, no. 8 (2021): 2079–87. http://dx.doi.org/10.1093/jac/dkab133.

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Abstract Objectives To evaluate Plasmodium malariae susceptibility to current and lead candidate antimalarial drugs. Methods We conducted cross-sectional screening and detection of all Plasmodium species malaria cases, which were nested within a longitudinal prospective study, and an ex vivo assessment of efficacy of a panel of antimalarials against P. malariae and Plasmodium falciparum, both PCR-confirmed mono-infections. Reference compounds tested included chloroquine, lumefantrine, artemether and piperaquine, while candidate antimalarials included the imidazolopiperazine GNF179, a close ana

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Kay, Katherine, Eva Maria Hodel, and Ian M. Hastings. "Improving the Role and Contribution of Pharmacokinetic Analyses in Antimalarial Drug Clinical Trials." Antimicrobial Agents and Chemotherapy 58, no. 10 (2014): 5643–49. http://dx.doi.org/10.1128/aac.02777-14.

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ABSTRACTIt is now World Health Organization (WHO) policy that drug concentrations on day 7 be measured as part of routine assessment in antimalarial drug efficacy trials. The rationale is that this single pharmacological measure serves as a simple and practical predictor of treatment outcome for antimalarial drugs with long half-lives. Herein we review theoretical data and field studies and conclude that the day 7 drug concentration (d7c) actually appears to be a poor predictor of therapeutic outcome. This poor predictive capability combined with the fact that many routine antimalarial trials

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Duncan, MR, and HA Capell. "The use of antimalarials in combination with other disease modifying agents in RA – the British experience." Lupus 5, no. 1_suppl (1996): 50–58. http://dx.doi.org/10.1177/0961203396005001121.

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Antimalarial drugs are effective disease modifying agents in RA with a low incidence of serious toxic effects. Recently, combinations of second-line agents have been used in RA in attempts to treat patients with no response to a number of single agents, or suboptimal response to a single agent. Combinations of drugs have been selected for maximum efficacy and minimum toxicity, but clinical trials are difficult to design and interpret. In particular, ensuring adequate power to detect small differences in response poses a major problem. Antimalarials are an attractive choice for combination ther

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Strangward, Patrick, Michael J. Haley, Manuel G. Albornoz, et al. "Targeting the IL33–NLRP3 axis improves therapy for experimental cerebral malaria." Proceedings of the National Academy of Sciences 115, no. 28 (2018): 7404–9. http://dx.doi.org/10.1073/pnas.1801737115.

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Cerebral malaria (CM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently, the only treatment for CM is the provision of antimalarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify potential improved treatments for CM, we performed a nonbiased whole-brain transcriptomic time-course analysis of antimalarial drug chemotherapy of murine experimental CM (ECM). Bioinformatics analyses revealed IL33 as a critical regulator of neuroinflammation and cerebral pathology that is down-regula

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Kulkeaw, Kasem. "Next-Generation Human Liver Models for Antimalarial Drug Assays." Antibiotics 10, no. 6 (2021): 642. http://dx.doi.org/10.3390/antibiotics10060642.

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Advances in malaria prevention and treatment have significantly reduced the related morbidity and mortality worldwide, however, malaria continues to be a major threat to global public health. Because Plasmodium parasites reside in the liver prior to the appearance of clinical manifestations caused by intraerythrocytic development, the Plasmodium liver stage represents a vulnerable therapeutic target to prevent progression. Currently, a small number of drugs targeting liver-stage parasites are available, but all cause lethal side effects in glucose-6-phosphate dehydrogenase-deficient individual

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Owolabi, Alíz T. Y., Sarah E. Reece, and Petra Schneider. "Daily rhythms of both host and parasite affect antimalarial drug efficacy." Evolution, Medicine, and Public Health 9, no. 1 (2021): 208–19. http://dx.doi.org/10.1093/emph/eoab013.

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ABSTRACT Background and objectives Circadian rhythms contribute to treatment efficacy in several non-communicable diseases. However, chronotherapy (administering drugs at a particular time-of-day) against infectious diseases has been overlooked. Yet, the daily rhythms of both hosts and disease-causing agents can impact the efficacy of drug treatment. We use the rodent malaria parasite Plasmodium chabaudi, to test whether the daily rhythms of hosts, parasites and their interactions affect sensitivity to the key antimalarial, artemisinin. Methodology Asexual malaria parasites develop rhythmicall

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JIMÉNEZ-DÍAZ, MARÍA BELÉN, SARA VIERA, ELENA FERNÁNDEZ-ALVARO, and IÑIGO ANGULO-BARTUREN. "Animal models of efficacy to accelerate drug discovery in malaria." Parasitology 141, no. 1 (2013): 93–103. http://dx.doi.org/10.1017/s0031182013000991.

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SUMMARYThe emergence of resistance to artemisinins and the renewed efforts to eradicate malaria demand the urgent development of new drugs. In this endeavour, the evaluation of efficacy in animal models is often a go/no go decision assay in drug discovery. This important role relies on the capability of animal models to assess the disposition, toxicology and efficacy of drugs in a single test. Although the relative merits of each efficacy model of malaria as human surrogate have been extensively discussed, there are no critical analyses on the use of such models in current drug discovery. In t

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Bakshi, R. P., E. Nenortas, A. K. Tripathi, D. J. Sullivan, and T. A. Shapiro. "Model System to Define Pharmacokinetic Requirements for Antimalarial Drug Efficacy." Science Translational Medicine 5, no. 205 (2013): 205ra135. http://dx.doi.org/10.1126/scitranslmed.3006684.

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Barnadas, Celine, Nicolas Senn, Jonah Iga, et al. "Plasmodium falciparum and Plasmodium vivax Genotypes and Efficacy of Intermittent Preventive Treatment in Papua New Guinea." Antimicrobial Agents and Chemotherapy 58, no. 11 (2014): 6958–61. http://dx.doi.org/10.1128/aac.03323-14.

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ABSTRACTIntermittent preventive treatment of infants (IPTi) reduces early childhood malaria-related morbidity. While genotypic drug resistance markers have proven useful in predicting the efficacy of antimalarial drugs in case management, there are few equivalent data relating to their protective efficacy when used as IPTi. The present data from an IPTi trial in Papua New Guinea demonstrate how these markers can predict protective efficacy of IPTi for bothPlasmodium falciparumandPlasmodium vivax.

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Nandal, Rimmy, Aakash Deep, Ishwar Singh, et al. "Synthesis of Metal Complexes of Primaquine and In-vitro Antimalarial Evaluation Against Plasmodium falciparum." Current Bioactive Compounds 15, no. 6 (2020): 631–36. http://dx.doi.org/10.2174/1573407214666180720124844.

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Background: Resistance to malarial drugs represents a major obstacle in the treatment of disease, thereby increasing the need for more efficient drugs. The development of metal complexes offers the medicinal chemist an opportunity to expand the activity of drugs. For providing supportive therapy to the host to boost its immune system several new antimalarial drugs are being beneath research, but sufficient information on their efficacy is yet not available. Methods: In view of above, eight drug metal complexes (Ba (II), Ca (II), Zn (II), St (II), Hg (II), Fe (III), Cu (II), Ni (II) of Sulfamet

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Summers, Kelly L. "A Structural Chemistry Perspective on the Antimalarial Properties of Thiosemicarbazone Metal Complexes." Mini-Reviews in Medicinal Chemistry 19, no. 7 (2019): 569–90. http://dx.doi.org/10.2174/1389557518666181015152657.

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Malaria is a potentially life-threatening disease, affecting approx. 214 million people worldwide. Malaria is caused by a protozoan, Plasmodium falciparum, which is transmitted through the Anopheles mosquito. Malaria treatment is becoming more challenging due to rising resistance against the antimalarial drug, chloroquine. Novel compounds that target aspects of parasite development are being explored in attempts to overcome this wide-spread problem. Anti-malarial drugs target specific aspects of parasite growth and development within the human host. One of the most effective targets is the inh

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Tanaka, Takeshi Q., W. Armand Guiguemde, David S. Barnett, et al. "Potent Plasmodium falciparum Gametocytocidal Activity of Diaminonaphthoquinones, Lead Antimalarial Chemotypes Identified in an Antimalarial Compound Screen." Antimicrobial Agents and Chemotherapy 59, no. 3 (2014): 1389–97. http://dx.doi.org/10.1128/aac.01930-13.

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ABSTRACTForty percent of the world's population is threatened by malaria, which is caused byPlasmodiumparasites and results in an estimated 200 million clinical cases and 650,000 deaths each year. Drug resistance has been reported for all commonly used antimalarials and has prompted screens to identify new drug candidates. However, many of these new candidates have not been evaluated against the parasite stage responsible for transmission, gametocytes. IfPlasmodium falciparumgametocytes are not eliminated, patients continue to spread malaria for weeks after asexual parasite clearance. Asymptom

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Blank, Brian R., Ryan L. Gonciarz, Poulami Talukder, et al. "Antimalarial Trioxolanes with Superior Drug-Like Properties and In Vivo Efficacy." ACS Infectious Diseases 6, no. 7 (2020): 1827–35. http://dx.doi.org/10.1021/acsinfecdis.0c00064.

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Naidoo, I., C. Roper, and B. L. Sharp. "COLLATION AND SPATIAL MAPPING OF PAN-AFRICAN ANTIMALARIAL DRUG EFFICACY DATA." Epidemiology 16, no. 5 (2005): S46. http://dx.doi.org/10.1097/00001648-200509000-00106.

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Konji, Sandra M. "An Overview of the Malaria Epidemic in Sub-Saharan Africa." Revue interdisciplinaire des sciences de la santé - Interdisciplinary Journal of Health Sciences 6, no. 1 (2016): 48–51. http://dx.doi.org/10.18192/riss-ijhs.v6i1.1491.

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Malaria is a parasitic disease that is transmitted by mosquitos during their blood meal. The risk of contracting malaria is highest for people in tropical countries, due to the ever-present humid weather that allows yearly infections. Consequently, sub-Saharan Africa has a disproportionately higher rate of death among women and children with malaria. One of the major barriers identified in the efficacy of malaria treatment and prevention is the lack of health education and literacy. The lack of health education has decreased the efficacy of antimalarial drugs, such as Artemether Lumefantrine,

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Sanz, Laura M., M. Belen Jiménez-Díaz, Benigno Crespo, et al. "Cyclopropyl Carboxamides, a Chemically Novel Class of Antimalarial Agents Identified in a Phenotypic Screen." Antimicrobial Agents and Chemotherapy 55, no. 12 (2011): 5740–45. http://dx.doi.org/10.1128/aac.05188-11.

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ABSTRACTMalaria is one of the deadliest infectious diseases in the world, with the eukaryotic parasitePlasmodium falciparumcausing the most severe form of the disease. Discovery of new classes of antimalarial drugs has become an urgent task to counteract the increasing problem of drug resistance. Screening directly for compounds able to inhibit parasite growthinvitrois one of the main approaches the malaria research community is now pursuing for the identification of novel antimalarial drug leads. Very recently, thousands of compounds with potent activity against the parasiteP. falciparumhave

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Pradines, Bruno, Christophe Rogier, Thierry Fusai, et al. "In Vitro Activities of Antibiotics againstPlasmodium falciparum Are Inhibited by Iron." Antimicrobial Agents and Chemotherapy 45, no. 6 (2001): 1746–50. http://dx.doi.org/10.1128/aac.45.6.1746-1750.2001.

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ABSTRACT The in vitro activities of cyclines (tetracycline, doxycycline, minocycline, oxytetracycline, and rolitetracycline), macrolides (erythromycin, spiramycin, roxithromycin, and lincomycin), quinolones (norfloxacin and ofloxacin), rifampin, thiamphenicol, tobramycin, metronidazole, vancomycin, phosphomycin, and cephalosporins (cephalexin, cefaclor, cefamandole, cefuroxime, ceftriazone, cefotaxime, and cefoxitin) were evaluated onPlasmodium falciparum clones, using an isotopic, micro-drug susceptibility test. Only tetracyclines, macrolides, quinolones, and rifampin demonstrated in vitro ac

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Orwa, Titus Okello, Rachel Waema Mbogo, and Livingstone Serwadda Luboobi. "Multiple-Strain Malaria Infection and Its Impacts on Plasmodium falciparum Resistance to Antimalarial Therapy: A Mathematical Modelling Perspective." Computational and Mathematical Methods in Medicine 2019 (June 11, 2019): 1–26. http://dx.doi.org/10.1155/2019/9783986.

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The emergence of parasite resistance to antimalarial drugs has contributed significantly to global human mortality and morbidity due to malaria infection. The impacts of multiple-strain malarial parasite infection have further generated a lot of scientific interest. In this paper, we demonstrate, using the epidemiological model, the effects of parasite resistance and competition between the strains on the dynamics and control of Plasmodium falciparum malaria. The analysed model has a trivial equilibrium point which is locally asymptotically stable when the parasite’s effective reproduction num

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Moore, Brioni R., Kenneth F. Ilett, Madhu Page-Sharp, Jeffrey D. Jago, and Kevin T. Batty. "Piperaquine Pharmacodynamics and Parasite Viability in a Murine Malaria Model." Antimicrobial Agents and Chemotherapy 53, no. 7 (2009): 2707–13. http://dx.doi.org/10.1128/aac.00056-09.

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ABSTRACT Piperaquine (PQ) is an important partner drug in antimalarial combination treatments, but the long half-life of PQ raises concerns about drug resistance. Our aim was to investigate the extended antimalarial effect of PQ in a study of drug efficacy, reinoculation outcomes, and parasite viability after the administration of a single dose of PQ in the murine malaria model. Initially, male Swiss mice were inoculated with Plasmodium berghei and at 64 h after parasite inoculation were given PQ phosphate at 90 mg/kg of body weight intraperitoneally. Parasite viability, drug efficacy, reinocu

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Kay, Katherine, Eva Maria Hodel, and Ian M. Hastings. "Altering Antimalarial Drug Regimens May Dramatically Enhance and Restore Drug Effectiveness." Antimicrobial Agents and Chemotherapy 59, no. 10 (2015): 6419–27. http://dx.doi.org/10.1128/aac.00482-15.

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ABSTRACTThere is considerable concern that malaria parasites are starting to evolve resistance to the current generation of antimalarial drugs, the artemisinin-based combination therapies (ACTs). We use pharmacological modeling to investigate changes in ACT effectiveness likely to occur if current regimens are extended from 3 to 5 days or, alternatively, given twice daily over 3 days. We show that the pharmacology of artemisinins allows both regimen changes to substantially increase the artemisinin killing rate. Malaria patients rarely contain more than 1012parasites, while the standard dosing

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Sanders, Natalie G., David J. Meyers, and David J. Sullivan. "Antimalarial Efficacy of Hydroxyethylapoquinine (SN-119) and Its Derivatives." Antimicrobial Agents and Chemotherapy 58, no. 2 (2013): 820–27. http://dx.doi.org/10.1128/aac.01704-13.

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ABSTRACTQuinine and other cinchona-derived alkaloids, although recently supplanted by the artemisinins (ARTs), continue to be important for treatment of severe malaria. Quinine and quinidine have narrow therapeutic indices, and a safer quinine analog is desirable, particularly with the continued threat of antimalarial drug resistance. Hydroxyethylapoquinine (HEAQ), used at 8 g a day for dosing in humans in the 1930s and halving mortality from bacterial pneumonias, was shown to cure bird malaria in the 1940s and was also reported as treatment for human malaria cases. Here we describe synthesis

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Birrell, Geoffrey W., Matthew P. Challis, Amanda De Paoli, et al. "Multi-omic Characterization of the Mode of Action of a Potent New Antimalarial Compound, JPC-3210, Against Plasmodium falciparum." Molecular & Cellular Proteomics 19, no. 2 (2019): 308–25. http://dx.doi.org/10.1074/mcp.ra119.001797.

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The increasing incidence of antimalarial drug resistance to the first-line artemisinin combination therapies underpins an urgent need for new antimalarial drugs, ideally with a novel mode of action. The recently developed 2-aminomethylphenol, JPC-3210, (MMV 892646) is an erythrocytic schizonticide with potent in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, low cytotoxicity, potent in vivo efficacy against murine malaria, and favorable preclinical pharmacokinetics including a lengthy plasma elimination half-life. To investigate the impact of JPC-3210 on b

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Hastings, Ian M., William M. Watkins, and Nicholas J. White. "The evolution of drug–resistant malaria: the role of drug elimination half–life." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 357, no. 1420 (2002): 505–19. http://dx.doi.org/10.1098/rstb.2001.1036.

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This paper seeks to define and quantify the influence of drug elimination half–life on the evolution of antimalarial drug resistance. There are assumed to be three general classes of susceptibility of the malaria parasite Plasmodium falciparum to a drug: Res0 , the original, susceptible wildtype; Res1 , a group of intermediate levels of susceptibility that are more tolerant of the drug but still cleared by treatment; and Res2 , which is completely resistant to the drug. Res1 and Res2 resistance both evolve much faster if the antimalarial drug has a long half–life. We show that previous models

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Zamani, Zahra, Alireza Sadeghi Tafreshi, Hossein Nahrevanian, et al. "Efficacy of Eosin B as a New Antimalarial Drug in a Murine Model." Malaria Research and Treatment 2012 (December 16, 2012): 1–5. http://dx.doi.org/10.1155/2012/381724.

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The initial success of any adopted anti-infective strategy to malaria is followed by a descent due to the emergence of resistance to it. The search for new drugs and drug targets is a consistent demand in this disease. Eosin B, a common laboratory dye, is reported to have good antiparasitic properties in vitro. It was studied for its antiparasitic effect in vivo on chloroquine-sensitive Plasmodium berghei murine malaria. Eosin B was administered in 2 different doses by either the oral or parenteral route, once or twice daily to mice infected with Plasmodium berghei. Both the doses of eosin B 4

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Zottig, Victor E., Katherine A. Carr, John G. Clarke, Moshe J. Shmuklarsky, and Mara Kreishman-Deitrick. "Army Antimalarial Drug Development: An Advanced Development Case Study for Tafenoquine." Military Medicine 185, Supplement_1 (2020): 617–23. http://dx.doi.org/10.1093/milmed/usz304.

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Abstract Malaria is classified as a top-tier infectious disease threat associated with a high risk for mortality among U.S. service members deployed overseas. As malarial drug resistance degrades the efficacy of current gold standard drugs for malarial prophylaxis and treatment, it is vitally important to maintain a robust drug pipeline to discover and develop improved, next-generation antimalarial prevention and treatment tools. The U.S. Army Medical Materiel Development Activity (USAMMDA) manages the medical product development of the malarial drug tafenoquine for malarial prophylaxis to add

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Parapini, Silvia, Piero Olliaro, Visweswaran Navaratnam, Donatella Taramelli, and Nicoletta Basilico. "Stability of the Antimalarial Drug Dihydroartemisinin under Physiologically Relevant Conditions: Implications for Clinical Treatment and Pharmacokinetic andIn VitroAssays." Antimicrobial Agents and Chemotherapy 59, no. 7 (2015): 4046–52. http://dx.doi.org/10.1128/aac.00183-15.

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ABSTRACTArtemisinins are peroxidic antimalarial drugs known to be very potent but highly chemically unstable; they degrade in the presence of ferrous iron, Fe(II)-heme, or biological reductants. Less documented is how this translates into chemical stability and antimalarial activity across a range of conditions applying toin vitrotesting and clinical situations. Dihydroartemisinin (DHA) is studied here because it is an antimalarial drug on its own and the main metabolite of other artemisinins. The behaviors of DHA in phosphate-buffered saline, plasma, or erythrocyte lysate at different tempera

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Dziekan, Jerzy M., Han Yu, Dan Chen, et al. "Identifying purine nucleoside phosphorylase as the target of quinine using cellular thermal shift assay." Science Translational Medicine 11, no. 473 (2019): eaau3174. http://dx.doi.org/10.1126/scitranslmed.aau3174.

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Mechanisms of action (MoAs) have been elusive for most antimalarial drugs in clinical use. Decreasing responsiveness to antimalarial treatments stresses the need for a better resolved understanding of their MoAs and associated resistance mechanisms. In the present work, we implemented the cellular thermal shift assay coupled with mass spectrometry (MS-CETSA) for drug target identification inPlasmodium falciparum, the main causative agent of human malaria. We validated the efficacy of this approach for pyrimethamine, a folic acid antagonist, and E64d, a broad-spectrum cysteine proteinase inhibi

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RUEBUSH, TRENTON K., RODOLFO VILLAROEL, CÉSAR DÍAZ, et al. "PRACTICAL ASPECTS OF IN VIVO ANTIMALARIAL DRUG EFFICACY TESTING IN THE AMERICAS." American Journal of Tropical Medicine and Hygiene 68, no. 4 (2003): 391–97. http://dx.doi.org/10.4269/ajtmh.2003.68.391.

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Fotoran, Wesley L., Thomas Müntefering, Nicole Kleiber, et al. "A multilamellar nanoliposome stabilized by interlayer hydrogen bonds increases antimalarial drug efficacy." Nanomedicine: Nanotechnology, Biology and Medicine 22 (November 2019): 102099. http://dx.doi.org/10.1016/j.nano.2019.102099.

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Lee, Sulggi A., Adoke Yeka, Samuel L. Nsobya, et al. "Complexity ofPlasmodium falciparumInfections and Antimalarial Drug Efficacy at 7 Sites in Uganda." Journal of Infectious Diseases 193, no. 8 (2006): 1160–63. http://dx.doi.org/10.1086/501473.

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Mott, Bryan T., Abhai Tripathi, Maxime A. Siegler, Cathy D. Moore, David J. Sullivan, and Gary H. Posner. "Synthesis and Antimalarial Efficacy of Two-Carbon-Linked, Artemisinin-Derived Trioxane Dimers in Combination with Known Antimalarial Drugs." Journal of Medicinal Chemistry 56, no. 6 (2013): 2630–41. http://dx.doi.org/10.1021/jm400058j.

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Neto, Zoraima, Marta Machado, Ana Lindeza, Virgílio do Rosário, Marcos L. Gazarini, and Dinora Lopes. "Treatment ofPlasmodium chabaudiParasites with Curcumin in Combination with Antimalarial Drugs: Drug Interactions and Implications on the Ubiquitin/Proteasome System." Journal of Parasitology Research 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/429736.

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Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT) is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin againstPlasmodiumspp. Drug interaction assays between curcumin/piperine/chloroquine and curcumin/piperine/artemisinin combinations and the potential of drug treatment to interfere with the ubiquitin proteasome system (UPS) were analyzed.In vivoefficacy of curcumin was studied in BALB/c mice infected withPlasmodium chabaudiclones resistant to chloro

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Upton, L. M., P. M. Brock, T. S. Churcher, et al. "Lead Clinical and Preclinical Antimalarial Drugs Can Significantly Reduce Sporozoite Transmission to Vertebrate Populations." Antimicrobial Agents and Chemotherapy 59, no. 1 (2014): 490–97. http://dx.doi.org/10.1128/aac.03942-14.

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ABSTRACTTo achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examine

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Duan, Shuai, Ruili Wang, Rongrong Wang, et al. "In vivo antimalarial activity and pharmacokinetics of artelinic acid-choline derivative liposomes in rodents." Parasitology 147, no. 1 (2019): 58–64. http://dx.doi.org/10.1017/s0031182019001306.

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AbstractIt is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppres

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Magill, Alan J., Jorge Zegarra, Coralith Garcia, Wilmer Marquiño, and Trenton K. Ruebush II. "Efficacy of sulfadoxine-pyrimethamine and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon basin of Peru." Revista da Sociedade Brasileira de Medicina Tropical 37, no. 3 (2004): 279–81. http://dx.doi.org/10.1590/s0037-86822004000300015.

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In vivo antimalarial drug efficacy studies of uncomplicated Plasmodium falciparum malaria at an isolated site in the Amazon basin of Peru bordering Brazil and Colombia showed >50% RII/RIII resistance to sulfadoxine-pyrimethamine but no evidence of resistance to mefloquine.

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Rajendran, Vinoth, Shilpa Rohra, Mohsin Raza, Gulam Mustafa Hasan, Suparna Dutt, and Prahlad C. Ghosh. "Stearylamine Liposomal Delivery of Monensin in Combination with Free Artemisinin Eliminates Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection in Murine Malaria." Antimicrobial Agents and Chemotherapy 60, no. 3 (2015): 1304–18. http://dx.doi.org/10.1128/aac.01796-15.

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The global emergence of drug resistance in malaria is impeding the therapeutic efficacy of existing antimalarial drugs. Therefore, there is a critical need to develop an efficient drug delivery system to circumvent drug resistance. The anticoccidial drug monensin, a carboxylic ionophore, has been shown to have antimalarial properties. Here, we developed a liposome-based drug delivery of monensin and evaluated its antimalarial activity in lipid formulations of soya phosphatidylcholine (SPC) cholesterol (Chol) containing either stearylamine (SA) or phosphatidic acid (PA) and different densities

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Heller, Laura E., and Paul D. Roepe. "Artemisinin-Based Antimalarial Drug Therapy: Molecular Pharmacology and Evolving Resistance." Tropical Medicine and Infectious Disease 4, no. 2 (2019): 89. http://dx.doi.org/10.3390/tropicalmed4020089.

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The molecular pharmacology of artemisinin (ART)-based antimalarial drugs is incompletely understood. Clinically, these drugs are used in combination with longer lasting partner drugs in several different artemisinin combination therapies (ACTs). ACTs are currently the standard of care against Plasmodium falciparum malaria across much of the world. A harbinger of emerging artemisinin resistance (ARTR), known as the delayed clearance phenotype (DCP), has been well documented in South East Asia (SEA) and is beginning to affect the efficacy of some ACTs. Though several genetic mutations have been

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