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drug resistance

NOT Open Access | Synthesis, structure-activity relationship and antimalarial efficacy of 6-chloro-2-arylvinylquinolines

September 23, 2020 - 09:30 -- NOT Open Access
Author(s): 
Huang G, Murillo Solano C, Yuan Y, et al.
Reference: 
J Med Chem. 2020 Sep 22

There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline UCF501 as a promising antimalarial compound.

Promising nanomaterials in the fight against malaria

September 23, 2020 - 08:50 -- Open Access
Author(s): 
Neves Borgheti-Cardoso L, San Anselmo M, Lantero E, Lancelot A, Serrano JL, Hernández-Ainsa S, Fernàndez-Busquets X, Sierra T
Reference: 
J Mater Chem B. 2020 Sep 21

For more than one hundred years, several treatments against malaria have been proposed but they have systematically failed, mainly due to the occurrence of drug resistance in part resulting from the exposure of the parasite to low drug doses. Several factors are behind this problem, including (i) the formidable barrier imposed by the Plasmodium life cycle with intracellular localization of parasites in hepatocytes and red blood cells, (ii) the adverse fluidic conditions encountered in the blood circulation that affect the interaction of molecular components with target cells, and (iii) the unfavorable physicochemical characteristics of most antimalarial drugs, which have an amphiphilic character and can be widely distributed into body tissues after administration and rapidly metabolized in the liver.

Distribution pattern of amino acid mutations in chloroquine and antifolate drug resistance associated genes in complicated and uncomplicated Plasmodium vivax isolates from Chandigarh, North India

September 16, 2020 - 13:09 -- Open Access
Author(s): 
Kaur H, Sehgal R, Kumar A, Bharti PK, Bansal D, Mohapatra PK, Mahanta J, Sultan AA
Reference: 
BMC Infect Dis. 2020 Sep 15;20(1):671

The increasing antimalarial drug resistance is a significant hindrance to malaria control and elimination programs. For the last six decades, chloroquine (CQ) plus pyrimethamine remains the first-line treatment for P. vivax malaria. Regions where both P. falciparum and P. vivax co-exist, P. vivax is exposed to antifolate drugs due to either misdiagnosis or improper treatment that causes selective drug pressure to evolve. Therefore, the present study aims to estimate antimalarial drug resistance among the complicated and uncomplicated P. vivax patients.

NOT Open Access | Humanized Mice and the Rebirth of Malaria Genetic Crosses

September 15, 2020 - 15:07 -- NOT Open Access
Author(s): 
Vendrely KM, Kumar S, Li X, Vaughan AM
Reference: 
Trends Parasitol. 2020 Sep 2:S1471-4922(20)30192-6

The first experimental crosses carried out with the human malaria parasite Plasmodium falciparum played a key role in determining the genetic loci responsible for drug resistance, virulence, invasion, growth rate, and transmission.

NOT Open Access | Molecular Mechanisms of Drug Resistance in Plasmodium falciparum Malaria

September 10, 2020 - 14:25 -- NOT Open Access
Author(s): 
Wicht KJ, Mok S, Fidock DA
Reference: 
Annu Rev Microbiol. 2020 Sep 8;74:431-454

Understanding and controlling the spread of antimalarial resistance, particularly to artemisinin and its partner drugs, is a top priority. Plasmodium falciparum parasites resistant to chloroquine, amodiaquine, or piperaquine harbor mutations in the P. falciparum chloroquine resistance transporter (PfCRT), a transporter resident on the digestive vacuole membrane that in its variant forms can transport these weak-base 4-aminoquinoline drugs out of this acidic organelle, thus preventing these drugs from binding heme and inhibiting its detoxification.

Not Open Access | Genomic Approaches to Drug Resistance in Malaria

September 10, 2020 - 14:21 -- NOT Open Access
Author(s): 
Rocamora F, Winzeler EA
Reference: 
Annu Rev Microbiol. 2020 Sep 8;74:761-786

Although the last two decades have seen a substantial decline in malaria incidence and mortality due to the use of insecticide-treated bed nets and artemisinin combination therapy, the threat of drug resistance is a constant obstacle to sustainable malaria control. Given that patients can die quickly from this disease, public health officials and doctors need to understand whether drug resistance exists in the parasite population, as well as how prevalent it is so they can make informed decisions about treatment.

NOT Open Access | Targeting and inhibiting Plasmodium falciparum using ultra-small gold nanoparticles

September 5, 2020 - 14:36 -- NOT Open Access
Author(s): 
Varela-Aramburu S, Ghosh C, Goerdeler F, Priegue P, Moscovitz O, Seeberger PH
Reference: 
ACS Appl Mater Interfaces. 2020 Sep 2

Malaria, a mosquito-borne disease caused by the Plasmodium species, claims more than 400,000 lives globally each year. Increasing drug resistance of the parasite renders the development of new anti-malaria drugs necessary. Alternatively, better delivery systems for already marketed drugs could help to solve the resistance problem. Herein, we report glucose-based ultra-small gold nanoparticles (Glc-NCs) that bind to cysteine-rich domains of Plasmodium falciparum surface proteins.

The potential antimalarial efficacy of hemocompatible silver nanoparticles from Artemisia species against P. falciparum parasite

September 2, 2020 - 08:39 -- Open Access
Author(s): 
Avitabile E, Senes N, D'Avino C, Tsamesidis I, Pinna A, Medici S, Pantaleo A
Reference: 
PLoS One. 2020 Sep 1;15(9):e0238532

Malaria represents one of the most common infectious diseases which becoming an impellent public health problem worldwide. Antimalarial classical medications include quinine-based drugs, like chloroquine, and artesunate, a derivative of artemisinin, a molecule found in the plant Artemisia annua. Such therapeutics are very effective but show heavy side effects like drug resistance. In this study, "green" silver nanoparticles (AgNPs) have been prepared from two Artemisia species (A. abrotanum and A. arborescens), traditionally used in folk medicine as a remedy for different conditions, and their potential antimalarial efficacy have been assessed.

Efficacy of artemether-lumefantrine for treating uncomplicated Plasmodium falciparum cases and molecular surveillance of drug resistance genes in Western Myanmar

September 1, 2020 - 09:43 -- Open Access
Author(s): 
Yanrui Wu, Myat Thut Soe, Pyae Linn Aung, Luyi Zhao, Weilin Zeng, Lynette Menezes, Zhaoqing Yang, Myat Phone Kyaw and Liwang Cui
Reference: 
Malaria Journal 2020 19:304, 27 August 2020

Currently, artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment in malaria-endemic areas. However, resistance in Plasmodium falciparum to artemisinin-based combinations emerging in the Greater Mekong Sub-region is a major problem hindering malaria elimination. To continuously monitor the potential spread of ACT-resistant parasites, this study assessed the efficacy of artemether-lumefantrine (AL) for falciparum malaria in western Myanmar.

NOT Open Access | Evaluation of the combination of azithromycin and naphthoquine in animal malaria models

August 26, 2020 - 14:41 -- NOT Open Access
Author(s): 
Bei ZC, Li GF, Zhao JH, Zhang M, Ji XG, Wang JY
Reference: 
Antimicrob Agents Chemother. 2020 Aug 24

Combination therapy using drugs with different mechanisms of action is the current state of the art in antimalarial treatment. However, except for artemisinin-based combination therapies, only few other combinations are available now. The increasing concern on the emergence and spread of artemisinin resistance in Plasmodium falciparum has evoked a need for the development of new antimalarials.

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