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Clinical Pharmacokinetics Jul 2020About one-sixth of the world's population is affected by a neglected tropical disease as defined by the World Health Organization and Center for Disease Control.... (Review)
Review
About one-sixth of the world's population is affected by a neglected tropical disease as defined by the World Health Organization and Center for Disease Control. Parasitic diseases comprise most of the neglected tropical disease list and they are causing enormous amounts of disability, morbidity, mortality, and healthcare costs worldwide. The burden of disease of the top five parasitic diseases has been estimated to amount to a total 23 million disability-adjusted life-years. Despite the massive health and economic impact, most drugs currently used for the treatment of parasitic diseases have been developed decades ago and insufficient novel drugs are being developed. The current review provides a compilation of the systemic and target-site pharmacokinetics of established antiparasitic drugs. Knowledge of the pharmacokinetic profile of drugs allows for the examination and possibly optimization of existing dosing schemes. Many symptoms of parasitic diseases are caused by parasites residing in different host tissues. Penetration of the antiparasitic drug into these tissues, the target site of infection, is a prerequisite for a successful treatment of the disease. Therefore, for the examination and improvement of established dosing regimens, not only the plasma but also the tissue pharmacokinetics of the drug have to be considered. For the current paper, almost 7000 scientific articles were identified and screened from which 429 were reviewed in detail and 100 were included in this paper. Systemic pharmacokinetics are available for most antiparasitic drugs but in many cases, not for all the relevant patient populations and only for single- or multiple-dose administration. Systemic pharmacokinetic data in patients with organ impairment and target-site pharmacokinetic data for relevant tissues and body fluids are mostly lacking. To improve the treatment of patients with parasitic diseases, research in these areas is urgently needed.
Topics: Antiparasitic Agents; Humans; Neglected Diseases; Parasitic Diseases; Tropical Medicine
PubMed: 32100246
DOI: 10.1007/s40262-020-00871-5 -
Marine Drugs Nov 2023Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable... (Review)
Review
Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. Marine-derived cyclic peptides have been increasingly screened as candidates for developing new drugs. Therefore, in this review, a systematic analysis of the scientific literature was performed and 25 marine-derived cyclic peptides with antiparasitic activity (-) were found. Antimalarial activity is the most reported (51%), followed by antileishmanial (27%) and antitrypanosomal (20%) activities. Some compounds showed promising antiparasitic activity at the nM scale, being active against various parasites. The mechanisms of action and targets for some of the compounds have been investigated, revealing different strategies against parasites.
Topics: Humans; Antiparasitic Agents; Peptides, Cyclic; Leishmaniasis; Antiprotozoal Agents; Parasitic Diseases
PubMed: 38132930
DOI: 10.3390/md21120609 -
Transactions of the Royal Society of... Mar 2022Ivermectin is a broad-spectrum antiparasitic agent that interferes with glutamate-gated chloride channels found in invertebrates but not in vertebrate species. Mass drug... (Review)
Review
Ivermectin is a broad-spectrum antiparasitic agent that interferes with glutamate-gated chloride channels found in invertebrates but not in vertebrate species. Mass drug administration (MDA) with ivermectin-based regimes has been a mainstay of elimination efforts targeting onchocerciasis and lymphatic filariasis for more than 3 decades. More recently, interest in the use of ivermectin to control other neglected tropical diseases (NTDs) such as soil-transmitted helminths and scabies has grown. Interest has been further stimulated by the fact that ivermectin displays endectocidal efficacy against various Anopheles species capable of transmitting malaria. Therefore there is growing interest in using ivermectin MDA as a tool that might aid in the control of both malaria and several NTDs. In this review we outline the evidence base to date on these emerging indications for ivermectin MDA with reference to clinical and public health data and discuss the rationale for evaluating the range of impacts of a malaria ivermectin MDA on other NTDs.
Topics: Animals; Antiparasitic Agents; Humans; Ivermectin; Malaria; Neglected Diseases; Onchocerciasis; Scabies
PubMed: 34323283
DOI: 10.1093/trstmh/trab114 -
Anais Da Academia Brasileira de Ciencias 2020COVID-19 emerged in December 2019 in China, and since then, has disrupted global public health and changed economic paradigms. In dealing with the new Coronavirus,... (Review)
Review
COVID-19 emerged in December 2019 in China, and since then, has disrupted global public health and changed economic paradigms. In dealing with the new Coronavirus, SARS-CoV-2, the world has not faced such extreme global fragility since the "Spanish flu" pandemic in 1918. Researchers globally are dedicating efforts to the search for an effective treatment for COVID-19. Drugs already used in a clinical setting for other pathologies have been tested as a new therapeutic approach against SARS-CoV-2, setting off a frenzy over the preliminary data of different studies. This work aims to compile and discuss the data published thus far. Despite the potential effects of some antivirals and antiparasitic against COVID-19, clinical studies must confirm real effectiveness. However, non-pharmacological approaches have proven to be the most efficient strategy to date.
Topics: Anti-Bacterial Agents; Antiparasitic Agents; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Macrolides; Pandemics; Pneumonia, Viral; SARS-CoV-2; Serine Proteinase Inhibitors
PubMed: 32556054
DOI: 10.1590/0001-3765202020200466 -
Science (New York, N.Y.) Jun 2023Cyanotriazole compounds "poison" topoisomerase II of pathogenic trypanosomatids.
Cyanotriazole compounds "poison" topoisomerase II of pathogenic trypanosomatids.
Topics: Antiparasitic Agents; DNA Topoisomerases, Type II; Triazoles; Topoisomerase II Inhibitors; Trypanosomatina; Animals; Humans
PubMed: 37384682
DOI: 10.1126/science.adi5925 -
Molecules (Basel, Switzerland) Nov 2023(indolyl)methanes (BIMs) are a class of compounds that have been recognized as an important core in the design of drugs with important pharmacological properties, such...
(indolyl)methanes (BIMs) are a class of compounds that have been recognized as an important core in the design of drugs with important pharmacological properties, such as promising anticancer and antiparasitic activities. Here, we explored the biological activity of the BIM core functionalized with different (hetero)aromatic moieties. We synthesized substituted BIM derivatives with triphenylamine, -dimethyl-1-naphthylamine and 8-hydroxylquinolyl groups, studied their photophysical properties and evaluated their in vitro antiproliferative and antiparasitic activities. The triphenylamine BIM derivative displayed an IC of 3.21, 3.30 and 3.93 μM against , and HT-29 cancer cell line, respectively. The selectivity index demonstrated that compound was up to eight-fold more active against the parasites and HT-29 than against the healthy cell line MRC-5. Fluorescence microscopy studies with MRC-5 cells and parasites incubated with derivative indicate that the compound seems to accumulate in the cell's mitochondria and in the parasite's nucleus. In conclusion, the BIM scaffold functionalized with the triphenylamine moiety proved to be the most promising antiparasitic and anticancer agent of this series.
Topics: Humans; Antiparasitic Agents; Methane; Trypanosoma brucei brucei; Antineoplastic Agents; Neoplasms; Structure-Activity Relationship
PubMed: 38067459
DOI: 10.3390/molecules28237728 -
Molecules (Basel, Switzerland) Nov 2020, a common saprobic filamentous fungus, not only plays an important role in biological control, but also has applications in medicine, food, and environmental... (Review)
Review
, a common saprobic filamentous fungus, not only plays an important role in biological control, but also has applications in medicine, food, and environmental protection. In this paper, 223 secondary metabolites and their bioactivities from 13 known species and various unidentified strains of are reviewed. Their structures can be described as polyketide, terpenoid, peptide, alkaloid, quinone, pyrone, sterol, and fatty acid. They have been demonstrated varying biological activities, including antimicrobial, antitumor, insecticidal, antiplasmodial, antimalarial, nematicidal, herbicidal, and enzyme-inhibiting. This review provides a comprehensive overview of secondary metabolites and their biological activities from strains of .
Topics: Antineoplastic Agents; Antiparasitic Agents; Enzyme Inhibitors; Herbicides; Insecticides; Paecilomyces; Secondary Metabolism
PubMed: 33139652
DOI: 10.3390/molecules25215077 -
Molecules (Basel, Switzerland) Jul 2021A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and...
A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against and intracellular amastigotes, against and against different developmental stages of . The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure-activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two strains and strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC) against THP-1 macrophages ranged between 50 and 100 μM. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases.
Topics: Antiparasitic Agents; Chagas Disease; Click Chemistry; Drug Design; Humans; Leishmania; Leishmaniasis; Macrophages; Phospholipids; Structure-Activity Relationship; Trypanosoma cruzi
PubMed: 34299479
DOI: 10.3390/molecules26144204 -
Molecules (Basel, Switzerland) Feb 2020Essential oils (EOs) have for a long time been recognized to possess several different biological activities. Several among these secondary plant metabolites exhibit...
Essential oils (EOs) have for a long time been recognized to possess several different biological activities. Several among these secondary plant metabolites exhibit marked antimicrobial effects that have made their use as an antiseptic and/or preservative in food well known, since the ancient times [...].
Topics: Anti-Bacterial Agents; Antiparasitic Agents; Microbial Sensitivity Tests; Oils, Volatile; Parasitic Sensitivity Tests; Parasympatholytics; Plant Oils
PubMed: 32033336
DOI: 10.3390/molecules25030678 -
Archives of Razi Institute Dec 2022Parasitic infections are one of the main problems in sheep breeding farms. For this reason, in order to control the damage caused by parasitic infections, a wide range...
Parasitic infections are one of the main problems in sheep breeding farms. For this reason, in order to control the damage caused by parasitic infections, a wide range of antiparasitic drugs with different forms are used. A particular area is important due to contamination with radioactive substances and its effect on the immune system of livestock in the area. Therefore, the aim of the present study was the effectiveness of antiparasitic drugs in sheep farms in Kazakhstan. In the current study, 3 groups of lambs were evaluated; each one included 30 infected lambs of 5 to 6 months with and and treated with antiparasitic compounds in two forms of tablets (Albendazole, Pyrantel, Ivermectin, Phenasal) and mineral-salt cube (Albenvet, Trimeratinvet). The result of the study showed that began 10, 20, and 30 days after experimentation, the mineral-salt cube significantly reduced the number of helminths and in sheep (92.18%) (≤0.05). Ant antiparasitic drugs in livestock diet are essential in reducing contamination and its effects on the herd.
Topics: Animals; Sheep; Eimeria; Coccidiosis; Strongyloides; Sheep Diseases; Feces; Antiparasitic Agents; Minerals
PubMed: 37274915
DOI: 10.22092/ARI.2022.360104.2552