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antimalarial drug

Building on Surface-Active Ionic Liquids for the Rescuing of the Antimalarial Drug Chloroquine

July 30, 2020 - 14:00 -- Open Access
Silva AT, Lobo L, Oliveira IS, Gomes J, Teixeira C, Nogueira F, Marques EF, Ferraz R, Gomes P
Int J Mol Sci. 2020 Jul 27;21(15):E5334

Ionic liquids derived from classical antimalarials are emerging as a new approach towards the cost-effective rescuing of those drugs. Herein, we disclose novel surface-active ionic liquids derived from chloroquine and natural fatty acids whose antimalarial activity in vitro was found to be superior to that of the parent drug.

NOT Open Access | β-Hydroxy- and β-Aminophosphonate Acyclonucleosides as Potent Inhibitors of Plasmodium falciparum Growth

July 21, 2020 - 15:21 -- NOT Open Access
Cheviet T, Wein S, Bourchenin G, Lagacherie M, Périgaud C, Cerdan R, Peyrottes S
J Med Chem. 2020 Jul 20

Malaria is an infectious disease caused by a parasite of the genus Plasmodium, and the emergence of parasites resistant to all current antimalarial drugs highlights the urgency of having new classes of molecules. We developed an effective method for the synthesis of a series of β-modified acyclonucleoside phosphonate (ANP) derivatives, using commercially available and inexpensive materials (i.e., aspartic acid and purine heterocycles).

BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic

July 13, 2020 - 16:17 -- Open Access
Sharma A, Kumar Sharma S, Shi Y, Bucci E, Carafoli E, Melino G, Bhattacherjee A, Das G
Cell Death Dis. 2020 Jul 8;11(7):516

Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed.

Evidence for Reduced Malaria Parasite Population after Application of Population-Level Antimalarial Drug Strategies in Southern Province, Zambia

July 7, 2020 - 12:48 -- Open Access
Daniels RF, Schaffner SF, Bennett A, Porter TR, Yukich JO, Mulube C, Mambwe B, Mwenda MC, Chishimba S, Bridges DJ, Moonga H, Hamainza B, Chizema Kawesha E, Miller JM, Steketee RW, Wirth DF, Eisele TP, Hartl DL, Volkman SK
Am. J. Trop. Med. Hyg., 00(0), 2020, pp. 1–8

A mass drug administration trial was carried out in Southern Province, Zambia, between 2014 and 2016, in conjunction with a standard of care package that included improved surveillance, increased access to malaria case management, and sustained high levels of vector control coverage. This was preceded by mass test and treatment in the same area from 2011 to 2013. Concordant decreases in malaria prevalence in Southern Province and deaths attributed to malaria in Zambia over this time suggest that these strategies successfully reduced the malaria burden.

NOT Open Access | Evolution of antimalarial drug resistance markers in the reservoir of Plasmodium falciparum infections in the Upper East Region of Ghana

May 29, 2020 - 14:38 -- NOT Open Access
Narh CA, Ghansah A, Duffy MF, Ruybal-Pesántez S, Onwona CO, Oduro AR, Koram KA, Day KP, Tiedje KE
J Infect Dis. 2020 May 27:jiaa286

The majority of Plasmodium falciparum infections, constituting the reservoir in all ages, are asymptomatic in high transmission settings in Africa. The role of this reservoir in the evolution and spread of drug resistance was explored.

A Computer Modelling Approach To Evaluate the Accuracy of Microsatellite Markers for Classification of Recurrent Infections during Routine Monitoring of Antimalarial Drug Efficacy

March 30, 2020 - 10:26 -- Open Access
Jones S, Plucinski M, Kay K, Hodel EM, Hastings IM
Antimicrob Agents Chemother. 2020 Mar 24;64(4). pii: e01517-19

Antimalarial drugs have long half-lives, so clinical trials to monitor their efficacy require long periods of follow-up to capture drug failure that may become patent only weeks after treatment. Reinfections often occur during follow-up, so robust methods of distinguishing drug failures (recrudescence) from emerging new infections are needed to produce accurate failure rate estimates. Molecular correction aims to achieve this by comparing the genotype of a patient’s pretreatment (initial) blood sample with that of any infection that occurs during follow-up, with matching genotypes indicating drug failure.

NOT Open Access | Fluorinated scaffolds for antimalarial drug discovery

March 24, 2020 - 12:25 -- NOT Open Access
Upadhyay C, Chaudhary M, De Oliveira RN, Borbas A, Kempaiah P, Rathi B
Expert Opin Drug Discov. 2020 Mar 21:1-14.

The unique physicochemical properties and chemical diversity of organofluorine compounds have remarkably contributed for their wide utility in the area of pharmaceuticals, materials and agrochemicals. The noteworthy characteristics of fluorine include high electron affinity, lipophilicity and bioavailability, extending the half-life of the drugs. The incorporation of fluorine substituents, particularly trifluoromethyl groups, into organic molecules has led to their high potency against various diseases, including malaria. Hence, organofluorinated molecules offer valuable avenues for the design of new drug candidates against malaria.

Combining Stage Specificity and Metabolomic Profiling to Advance Antimalarial Drug Discovery

March 2, 2020 - 14:02 -- Open Access
Murithi JM, Owen ES, Istvan ES, Lee MCS, Ottilie S, Chibale K, Goldberg DE, Winzeler EA, Llinás M, Fidock DA, Vanaerschot M
Cell Chem Biol. 2020 Feb 20;27(2):158-171.e3.

We report detailed susceptibility profiling of asexual blood stages of the malaria parasite Plasmodium falciparum to clinical and experimental antimalarials, combined with metabolomic fingerprinting. Results revealed a variety of stage-specific and metabolic profiles that differentiated the modes of action of clinical antimalarials including chloroquine, piperaquine, lumefantrine, and mefloquine, and identified late trophozoite-specific peak activity and stage-specific biphasic dose-responses for the mitochondrial inhibitors DSM265 and atovaquone.

Estimation of the In Vivo MIC of Cipargamin in Uncomplicated Plasmodium falciparum Malaria

January 24, 2017 - 18:20 -- Open Access
Tran Tinh Hien, Nicholas J. White, Kamal Hamed, et al.
Antimicrob. Agents Chemother. February 2017 vol. 61 no. 2 e01940-16

The MIC of an antimalarial drug for a particular infection is the drug level associated with a net parasite multiplication rate of one per asexual cycle.

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