Atovaquone-proguanil for treating uncomplicated Plasmodium falciparum malaria

Blanshard, Andrew; Hine, Paul

doi:10.1002/14651858.cd004529.pub3

Cited by 13 publications

(12 citation statements)

References 32 publications

(1 reference statement)

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“…Atovaquone is a well-tolerated antiparasitic drug used in the treatment of parasitic infections [20,31,32]. As a malaria prophylaxis, atovaquone is given in combination with proguanil-chloride (Malarone ® ) which are thought to act synergistically against the malaria parasite [33].…”

Section: Atovaquone and Proguanil Hydrochloride Function Together To Reduce Sars-cov-2 Infectious Particle Productionmentioning

confidence: 99%

Atovaquone and Berberine Chloride Reduce SARS-CoV-2 Replication In Vitro

Rodriguez-Rodriguez

Noval

Jang

et al. 2021

Viruses

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Epidemic RNA viruses seem to arise year after year leading to countless infections and devastating disease. SARS-CoV-2 is the most recent of these viruses, but there will undoubtedly be more to come. While effective SARS-CoV-2 vaccines are being deployed, one approach that is still missing is effective antivirals that can be used at the onset of infections and therefore prevent pandemics. Here, we screened FDA-approved compounds against SARS-CoV-2. We found that atovaquone, a pyrimidine biosynthesis inhibitor, is able to reduce SARS-CoV-2 infection in human lung cells. In addition, we found that berberine chloride, a plant-based compound used in holistic medicine, was able to inhibit SARS-CoV-2 infection in cells through direct interaction with the virion. Taken together, these studies highlight potential avenues of antiviral development to block emerging viruses. Such proactive approaches, conducted well before the next pandemic, will be essential to have drugs ready for when the next emerging virus hits.

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Section: Atovaquone and Proguanil Hydrochloride Function Together To Reduce Sars-cov-2 Infectious Particle Productionmentioning

confidence: 99%

Atovaquone and Berberine Chloride Reduce SARS-CoV-2 Replication In Vitro

Rodriguez-Rodriguez

Noval

Jang

et al. 2021

Viruses

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“…ACTs are already generally accepted as the best treatment regimens for uncomplicated Plasmodium falciparum malaria. They are more effective and have fewer adverse effects than other antimalarials such as atovaquone–proguanil, quinine or mefloquine [ 29 , 30 , 31 , 32 ]. The WHO recommends a total of six ACTs, of which countries can select first‐ and second‐line treatment [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Are national treatment guidelines for falciparum malaria in line with WHO recommendations and is antimalarial resistance taken into consideration? – A review of guidelines in non‐endemic countries

Visser

Zonneveld

Peto

et al. 2022

Tropical Med Int Health

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Objective Plasmodium falciparum infections are a relatively rare but potentially deadly disease found in returning travellers. We compare the national treatment guidelines of non‐endemic countries with the WHO guidelines for the treatment of Plasmodium falciparum infections. Methods Review. We identified non‐endemic countries with an incidence rate of imported malaria of at least one per 100,000 population and at least 50 cases annually. Using PubMed and Google Search, we reviewed national guidelines published before 1 March 2021. Results Thirteen guidelines were identified. For uncomplicated falciparum malaria, 11 of 13 countries (85%) recommend an artemisinin‐based combination therapy as first‐line regimen in adults, of which artemether–lumefantrine was the most common. For severe malaria, all guidelines recommend the use of intravenous artesunate. Only three countries adjust treatment recommendations based on expected artemisinin resistance. Conclusion Treatment guidelines for uncomplicated falciparum malaria in non‐endemic countries generally adhere to WHO recommendations but often fail to mention the risk of drug resistance in returning travellers. Artemisinin‐based Combination Therapies (ACTs) should be the first choice for all uncomplicated malaria cases. Furthermore, the choice between ACTs should be based on regional resistance patterns.

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“…Proguanil, originally developed as an antimalarial drug [5], has been documented with good anti-proliferative effects [7]. Compared to metformin, another biguanide compound, the effective antitumor concentration of proguanil is considerably low [7], and it has no side effect of lactic acidosis which appears on other biguanide drugs [22].…”

Section: Discussionmentioning

confidence: 99%

“…Proguanil, a member of the biguanide family, was originally developed as an anti-malarial drug [5]. Interestingly, we noticed that some studies reported that proguanil may exert anticancer effects by reducing tumor hypoxia, inducing mitochondrial dysfunction and oxidative stress, and causing DNA damage [6].…”

Section: Introductionmentioning

confidence: 99%

Proguanil synergistically sensitizes ovarian cancer cells to olaparib by increasing DNA damage and inducing apoptosis

Wu¹,

Wu²,

Hu³

et al. 2022

Int. J. Med. Sci.

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Ovarian cancer is the second leading cause of cancer-related deaths in women, with low five-year survival rates. Therefore, it is essential to seek new treatment options. Olaparib, a PARP inhibitor, has benefited many ovarian cancer patients, but olaparib is much less effective as a single agent in 50% of patients with high grade severe tumors. Proguanil, which was originally developed as an anti-malarial drug, has gained attention due to its anti-tumor effects. Here, we evaluated the anti-tumor effect of the combination of olaparib and proguanil on ovarian cancer cells, aimed to develop a potential medical option for treating ovarian cancer patients. We examined the effect on proliferation by MTT and colony formation assays, while cell migration was measured by the transwell assay. The effect on apoptosis was measured by flow cytometry and AO/EB staining assays. Western blotting was used to detect protein expression levels in cells treated with olaparib and/or proguanil. In addition, the synergistic effect of these two drugs is calculated by CompuSyn software. The combination of olaparib and proguanil significantly increased growth suppression and apoptosis in ovarian cancer cells, compared to either single agent alone. Furthermore, results showed that the combination of olaparib and proguanil synergistically increased olaparib-induced apoptosis and DNA damage and reduced the efficiency of DNA homologous recombination repair. Our findings indicate that combination of olaparib with proguanil will be a novel potential administration route for treating ovarian cancer patients.

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Atovaquone-proguanil for treating uncomplicated Plasmodium falciparum malaria

Cited by 13 publications

References 32 publications

Atovaquone and Berberine Chloride Reduce SARS-CoV-2 Replication In Vitro

Atovaquone and Berberine Chloride Reduce SARS-CoV-2 Replication In Vitro

Are national treatment guidelines for falciparum malaria in line with WHO recommendations and is antimalarial resistance taken into consideration? – A review of guidelines in non‐endemic countries

Proguanil synergistically sensitizes ovarian cancer cells to olaparib by increasing DNA damage and inducing apoptosis

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