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antimalarial drug

Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum

February 20, 2021 - 08:37 -- Open Access
Author(s): 
Akshaykumar Nayak, Himani Saxena, Chandramohan Bathula, Tarkeshwar Kumar, Souvik Bhattacharjee, Subhabrata Sen and Ashish Gupta
Reference: 
Malaria Journal 2021 20:100, 17 February 2021

Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment.

NOT Open Access | A tablet derived from Andrographis paniculata complements dihydroartemisinin-piperaquine treatment of malaria in pregnant mice

February 15, 2021 - 15:15 -- NOT Open Access
Author(s): 
Bastiana, Widyawaruyanti A, Ilmi H, Tumewu L, Prasetyo B, Hafid AF, Aryati
Reference: 
J Basic Clin Physiol Pharmacol. 2021 Feb 11

The use of standard antimalarial drugs, such as dihydroartemisinin-piperaquine (DHP) for the treatment of malaria during pregnancy is limited due to the risk of teratogenicity. The alternative is therefore required although few exist. Here we show a phytopharmaceutical drug derived from Andrographis paniculata (AS201-01), which is effective as herbal antimalarial both in vitro and in vivo and may be a suitable alternative when used in complementary treatment with DHP.

NOT Open Access | A novel antiplasmodial compound: integration of in silico and in vitro assays

February 10, 2021 - 09:51 -- NOT Open Access
Author(s): 
Costa Júnior DB, Araújo JSC, Oliveira LM, Neri FSM, Moreira POL, Taranto AG, Fonseca AL, Varotti FP, Leite FHA
Reference: 
J Biomol Struct Dyn. 2021 Feb 8:1-13

Malaria is a disease caused by Plasmodium genus. which P. falciparum is responsible for the most severe form of the disease, cerebral malaria. In 2018, 405,000 people died of malaria. Antimalarial drugs have serious adverse effects and limited efficacy due to multidrug-resistant strains. One way to overcome these limitations is the use of computational approaches for prioritizing candidates to phenotypic assays and/or in vitro assays against validated targets. Plasmodium falciparum Enoyl-ACP reductase (PfENR) is noteworthy because it catalyzes the rate-limiting step of the biosynthetic pathway of fatty acid.

NOT Open Access | Metalloaminopeptidases of the Protozoan Parasite Plasmodium falciparum as Targets for the Discovery of Novel Antimalarial Drugs

February 6, 2021 - 10:50 -- NOT Open Access
Author(s): 
Mills B, Isaac RE, Foster R
Reference: 
J Med Chem. 2021 Feb 3

Malaria poses a significant threat to approximately half of the world's population with an annual death toll close to half a million. The emergence of resistance to front-line antimalarials in the most lethal human parasite species, Plasmodium falciparum (Pf), threatens progress made in malaria control. The prospect of losing the efficacy of antimalarial drugs is driving the search for small molecules with new modes of action.

Parasite-host dynamics throughout antimalarial drug development stages complicate the translation of parasite clearance

February 2, 2021 - 16:29 -- Open Access
Author(s): 
Burgert L, Zaloumis S, Dini S, Marquart L, Cao P, Cherkaoui M, Gobeau N, McCarthy J, Simpson JA, Möhrle JJ, Penny MA
Reference: 
Antimicrob Agents Chemother. 2021 Feb 1:AAC.01539-20

Ensuring continued success against malaria depends on a pipeline of new antimalarials. Antimalarial drug development utilizes pre-clinical murine and experimental human malaria infection studies to evaluate drug efficacy. A sequential approach is typically adapted, with results from each stage, informing the design of the next stage of development. The validity of this approach depends on confidence that results from murine malarial studies predict the outcome of clinical trials in humans. Parasite clearance rates following treatment are key parameters of drug efficacy.

NOT Open Access | An insight into the recent development of the clinical candidates for the treatment of malaria and their target proteins

January 20, 2021 - 07:52 -- NOT Open Access
Author(s): 
Madhav H, Hoda N
Reference: 
Eur J Med Chem. 2021 Jan 15;210:112955

Malaria is an endemic disease, prevalent in tropical and subtropical regions which cost half of million deaths annually. The eradication of malaria is one of the global health priority nevertheless, current therapeutic efforts seem to be insufficient due to the emergence of drug resistance towards most of the available drugs, even first-line treatment ACT, unavailability of the vaccine, and lack of drugs with a new mechanism of action. Intensification of antimalarial research in recent years has resulted into the development of single dose multistage therapeutic agents which has advantage of overcoming the antimalarial drug resistance.

NOT Open Access | Current methods for the detection of antimalarial drug resistance in Plasmodium parasites infecting humans

January 20, 2021 - 07:07 -- NOT Open Access
Author(s): 
Slater L, Betson M, Ashraf S, Sargison N, Chaudhry U
Reference: 
Acta Trop. 2021 Jan 16:10582

Malaria is the world's deadliest parasitic disease. Great progress has been made in the fight against malaria over the past two decades, but this has recently begun to plateau, in part due to the global development of antimalarial drug resistance. The ability to track drug resistance is necessary to achieve progress in treatment, disease surveillance and epidemiology, which has prompted the development of advanced diagnostic methods. These new methods provide unprecedented access to information that can help to guide public health policies.

Monthly Malaria Prophylaxis Cuts Child Deaths in Sub-Saharan Africa

January 20, 2021 - 06:58 -- Open Access
Author(s): 
Kuehn BM
Reference: 
JAMA. 2021 Jan 19;325(3):213

Treating children in sub-Saharan Africa’s malaria-endemic areas with a monthly preventive drug regimen during the rainy season reduced children’s deaths from the disease by up to 57%, a study found.

Genetic diversity of the Plasmodium falciparum GTP-cyclohydrolase 1, dihydrofolate reductase and dihydropteroate synthetase genes reveals new insights into sulfadoxine-pyrimethamine antimalarial drug resistance

January 6, 2021 - 13:10 -- Open Access
Author(s): 
Turkiewicz A, Manko E, Sutherland CJ, Diez Benavente E, Campino S, Clark TG
Reference: 
PLoS Genet. 2020 Dec 31;16(12):e1009268

Plasmodium falciparum parasites resistant to antimalarial treatments have hindered malaria disease control. Sulfadoxine-pyrimethamine (SP) was used globally as a first-line treatment for malaria after wide-spread resistance to chloroquine emerged and, although replaced by artemisinin combinations, is currently used as intermittent preventive treatment of malaria in pregnancy and in young children as part of seasonal malaria chemoprophylaxis in sub-Saharan Africa. The emergence of SP-resistant parasites has been predominantly driven by cumulative build-up of mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps) genes, but additional amplifications in the folate pathway rate-limiting pfgch1 gene and promoter, have recently been described.

NOT Open Access | Chemotherapeutic and prophylactic antimalarial drugs induce cell death through mitochondrial-mediated apoptosis in murine models

January 6, 2021 - 13:06 -- NOT Open Access
Author(s): 
Olanlokun JO, Balogun FA, Olorunsogo OO
Reference: 
Drug Chem Toxicol. 2021 Jan;44(1):47-57

Malaria is a parasitic disease that has defied many treatment plans. This study was carried out to investigate the host mitochondrial response to malarial infection and selected antimalarial chemotherapy using murine models. The effects of artesunate (ART) and proguanil (PRG) on mitochondrial Permeability Transition (mPT), mitochondrial ATPase (mATPase), level of malondialdehyde (MDA) and activities of antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), Xanthine oxidase (XO), glutathione S-transferase (GST) and reduced glutathione (GSH) were estimated in Plasmodium berghei-infected mice treated with ART and PRG.

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