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Veterinary Parasitology Apr 2018Canine babesiosis is a tick-borne disease caused by several Babesia spp. which have different susceptebility to anti-protozoal drugs. A few drugs and drug combinations... (Review)
Review
Canine babesiosis is a tick-borne disease caused by several Babesia spp. which have different susceptebility to anti-protozoal drugs. A few drugs and drug combinations are used in the treatment of canine babesiosis often without complete parasite elimination leaving treated dogs as carriers which could relapse with clinical disease and also transmit infection further. Although the large form canine babesial species Babesia canis, Babesia vogeli and Babesia rossi are sensitive to the aromatic diamidines imidocarb dipropionate and diminazene aceturate, small form species such as Babesia gibsoni, Babesia conradae and Babesia vulpes (Theileria annae) are relatively resistant to these drugs and are treated with the combination of the hydroxynaphthoquinone atovaquone and the antibiotic azithromycin. Azithromycin and other antibiotics that have anti-protozoal properties target the apicoplast, a relict plastid found in protozoa, and exert a delayed death effect. The triple combination of clindamycin, diminazene aceturate and imidocarb dipropionate is also effective against B. gibsoni and used to treat atovaquone-resistant strains of this species. Novel drugs and the synergistic effects of drug combinations against Babesia infection should be explored further to find new treatments for canine babesiosis.
Topics: Animals; Antiprotozoal Agents; Babesia; Babesiosis; Dog Diseases; Dogs
PubMed: 29657012
DOI: 10.1016/j.vetpar.2018.03.001 -
Current Opinion in Infectious Diseases Oct 2021Substantial progress has been made recently on the development of new therapeutics for cryptosporidiosis, an infection by the protozoan parasite Cryptosporidium that is... (Review)
Review
PURPOSE OF REVIEW
Substantial progress has been made recently on the development of new therapeutics for cryptosporidiosis, an infection by the protozoan parasite Cryptosporidium that is associated with diarrhea, malnutrition, growth stunting, cognitive deficits, and oral vaccine failure in children living in low-resource settings.
RECENT FINDINGS
Various drug discovery approaches have generated promising lead candidates. The repurposed antimycobacterial drug clofazimine was tested in Malawian HIV patients with cryptosporidiosis but was ineffective. Target-based screens identified inhibitors of lysyl-tRNA synthetase, phenylalanyl-tRNA synthetase, methionyl-tRNA synthetase, and calcium-dependent protein kinase 1. Phenotypic screens led to discovery of a phosphatidylinositol 4-kinase inhibitor, the piperazine MMV665917, and the benzoxaborole AN7973. The relationship between pharmacokinetic properties and in-vivo efficacy is gradually emerging. A pathway to clinical trials, regulatory approval, and introduction has been proposed but additional work is needed to strengthen the route.
SUMMARY
Several lead compounds with potent activity in animal models and a favorable safety profile have been identified. A sustained effort will be required to advance at least one to clinical proof-of-concept studies. The demonstrated risk of resistance indicates multiple candidates should be advanced as potential components of a combination therapy.
Topics: Animals; Antiprotozoal Agents; Cryptosporidiosis; Cryptosporidium; Diarrhea; HIV Infections; Humans
PubMed: 34261904
DOI: 10.1097/QCO.0000000000000761 -
Molecules (Basel, Switzerland) Jan 2021Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis... (Review)
Review
Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis of the pharmacological potential of these natural products. According to PASS (Prediction of Activity Spectra for Substances) estimates, they are more likely to exhibit antiprotozoal and antitumor properties. Some of them are now widely used in clinical medicine. All polycyclic endoperoxides presented in this article demonstrate antiprotozoal activity and can be divided into three groups. The third group includes endoperoxides, which show weak antiprotozoal activity with a reliability of up to 70%, and this group includes only 1.1% of metabolites. The second group includes the largest number of endoperoxides, which are 65% and show average antiprotozoal activity with a confidence level of 70 to 90%. Lastly, the third group includes endoperoxides, which are 33.9% and show strong antiprotozoal activity with a confidence level of 90 to 99.6%. Interestingly, artemisinin and its analogs show strong antiprotozoal activity with 79 to 99.6% confidence against obligate intracellular parasites which belong to the genera Plasmodium, Toxoplasma, Leishmania, and Coccidia. In addition to antiprotozoal activities, polycyclic endoperoxides show antitumor activity in the proportion: 4.6% show weak activity with a reliability of up to 70%, 65.6% show an average activity with a reliability of 70 to 90%, and 29.8% show strong activity with a reliability of 90 to 98.3%. It should also be noted that some polycyclic endoperoxides, in addition to antiprotozoal and antitumor properties, show other strong activities with a confidence level of 90 to 97%. These include antifungal activity against the genera Aspergillus, Candida, and Cryptococcus, as well as anti-inflammatory activity. This review provides insights on further utilization of polycyclic endoperoxides by medicinal chemists, pharmacologists, and the pharmaceutical industry.
Topics: Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents; Antiprotozoal Agents; Biological Products; Humans; Peroxides
PubMed: 33525706
DOI: 10.3390/molecules26030686 -
Molecules (Basel, Switzerland) Jun 2016Adverse effects and drug resistance to the current onchopharmacologicals have increased the demand for alternative novel therapeutics. We herein introduce justicidin B,... (Review)
Review
Adverse effects and drug resistance to the current onchopharmacologicals have increased the demand for alternative novel therapeutics. We herein introduce justicidin B, an arylnaphthalen lignan isolated from different plant origins, especially Justicia, Phyllanthus, Haplophyllum and Linum species. This cyclolignan exhibits a wide array of biological properties ranges from piscicidal to antifungal, antiviral and antibacterial activities. Activity against Trypanosoma brucei makes justicidin B a potential antiprotozoal agent for the treatment of neglected tropical diseases. Pharmacological properties like antiplatelet, anti-inflammatory and bone resorption inhibition have been also attributed to justicidin B. This compound is a potent cytotoxic substance on several cell lines, especially chronic myeloid and chronic lymphoid leukemia. Pharmacological values, natural variation, as well as biotechnological production of justicidin B by plant cell, tissue and organ culture are also described in this review. Chemical characteristics and chromatographic methods to identify justicidin B and its biosynthetic pathway have been discussed. Different approaches to the total synthesis of justicidin B are compared. This review would shed light on the role of justicidin B as an intriguing natural compound and provides a chance to optimize conditions for industrial applications.
Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antiprotozoal Agents; Biological Products; Biosynthetic Pathways; Biotechnology; Chemistry; Dioxolanes; Humans; Lignans; Metabolomics; Plant Extracts; Platelet Aggregation Inhibitors; Toxicity Tests
PubMed: 27347906
DOI: 10.3390/molecules21070820 -
Marine Drugs Jan 2015Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic... (Review)
Review
Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the present.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antimalarials; Antimicrobial Cationic Peptides; Antiprotozoal Agents; Antiviral Agents; Aquatic Organisms; Porifera
PubMed: 25603351
DOI: 10.3390/md13010618 -
Marine Drugs Apr 2022This review is devoted to the study of the biological activity of polyether ionophores produced by bacteria, unicellular marine algae, red seaweeds, marine sponges, and... (Review)
Review
This review is devoted to the study of the biological activity of polyether ionophores produced by bacteria, unicellular marine algae, red seaweeds, marine sponges, and coelenterates. Biological activities have been studied experimentally in various laboratories, as well as data obtained using QSAR (Quantitative Structure-Activity Relationships) algorithms. According to the data obtained, it was shown that polyether toxins exhibit strong antibacterial, antimicrobial, antifungal, antitumor, and other activities. Along with this, it was found that natural polyether ionophores exhibit such properties as antiparasitic, antiprotozoal, cytostatic, anti-mycoplasmal, and antieczema activities. In addition, polyethers have been found to be potential regulators of lipid metabolism or inhibitors of DNA synthesis. Further study of the mechanisms of action and the search for new polyether ionophores and their derivatives may provide more effective therapeutic natural polyether ionophores for the treatment of cancer and other diseases. For some polyether ionophores, 3D graphs are presented, which demonstrate the predicted and calculated activities. The data presented in this review will be of interest to pharmacologists, chemists, practical medicine, and the pharmaceutical industry.
Topics: Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Humans; Ionophores; Neoplasms
PubMed: 35621943
DOI: 10.3390/md20050292 -
Marine Drugs May 2016Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances... (Review)
Review
Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. This review for the first time provides a comprehensive overview of antimicrobial compounds that are known to be produced by sponge-associated microbes. We discuss the current state-of-the-art by grouping the bioactive compounds produced by sponge-associated microorganisms in four categories: antiviral, antibacterial, antifungal and antiprotozoal compounds. Based on in vitro activity tests, identified targets of potent antimicrobial substances derived from sponge-associated microbes include: human immunodeficiency virus 1 (HIV-1) (2-undecyl-4-quinolone, sorbicillactone A and chartarutine B); influenza A (H1N1) virus (truncateol M); nosocomial Gram positive bacteria (thiopeptide YM-266183, YM-266184, mayamycin and kocurin); Escherichia coli (sydonic acid), Chlamydia trachomatis (naphthacene glycoside SF2446A2); Plasmodium spp. (manzamine A and quinolone 1); Leishmania donovani (manzamine A and valinomycin); Trypanosoma brucei (valinomycin and staurosporine); Candida albicans and dermatophytic fungi (saadamycin, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and YM-202204). Thirty-five bacterial and 12 fungal genera associated with sponges that produce antimicrobials were identified, with Streptomyces, Pseudovibrio, Bacillus, Aspergillus and Penicillium as the prominent producers of antimicrobial compounds. Furthemore culture-independent approaches to more comprehensively exploit the genetic richness of antimicrobial compound-producing pathways from sponge-associated bacteria are addressed.
Topics: Animals; Anti-Infective Agents; Antiprotozoal Agents; Bacteria; Bioprospecting; Fungi; Humans; Porifera
PubMed: 27144573
DOI: 10.3390/md14050087 -
Scientific Reports Jan 2021Three new compounds (1-3) with unusual skeletons were isolated from the n-hexane extract of the air-dried aerial parts of Hypericum scabrum. Compound 1 represents the...
Three new compounds (1-3) with unusual skeletons were isolated from the n-hexane extract of the air-dried aerial parts of Hypericum scabrum. Compound 1 represents the first example of an esterified polycyclic polyprenylated acylphloroglucinol that features a unique tricyclo-[4.3.1.1]-undecane skeleton. Compound 2 is a fairly simple MPAP, but with an unexpected cycloheptane ring decorated with prenyl substituents, and compound 3 has an unusual 5,5-spiroketal lactone core. Their structures were determined by extensive spectroscopic and spectrometric techniques (1D and 2D NMR, HRESI-TOFMS). Absolute configurations were established by ECD calculations, and the absolute structure of 2 was confirmed by a single crystal determination. Plausible biogenetic pathways of compounds 1-3 were also proposed. The in vitro antiprotozoal activity of the compounds against Trypanosoma brucei rhodesiense and Plasmodium falciparum and cytotoxicity against rat myoblast (L6) cells were determined. Compound 1 showed a moderate activity against T. brucei and P. falciparum, with IC values of 3.07 and 2.25 μM, respectively.
Topics: Antiprotozoal Agents; Biological Products; Biosynthetic Pathways; Hypericum; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Plant Extracts; Structure-Activity Relationship
PubMed: 33446755
DOI: 10.1038/s41598-020-79305-y -
Journal of Enzyme Inhibition and... Dec 2022Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1...
Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1 and N-4 and the nature of the chalcogen atom (S, Se). These compounds were evaluated towards and . Thiosemicarbazide showed the best trypanocidal profile (epimastigotes), similar to benznidazole (BZ): IC ()=28.72 μM (CL-B5 strain) and 33.65 μM (Y strain), IC (BZ)=25.31 μM (CL-B5) and 22.73 μM (Y); it lacked toxicity over mammalian cells (CC > 256 µM). Thiosemicarbazones , and showed remarkable trichomonacidal effects (IC=16.39, 14.84 and 14.89 µM) and no unspecific cytotoxicity towards Vero cells (CC ≥ 275 µM). Selenoisosters and presented a slightly enhanced activity (IC=11.10 and 11.02 µM, respectively). Hydrogenosome membrane potential and structural changes were analysed to get more insight into the trichomonacidal mechanism.
Topics: Antiprotozoal Agents; Dose-Response Relationship, Drug; Molecular Structure; Parasitic Sensitivity Tests; Semicarbazones; Structure-Activity Relationship; Trichomonas vaginalis; Trypanosoma cruzi
PubMed: 35193444
DOI: 10.1080/14756366.2022.2041629 -
Clinical Pharmacokinetics Feb 2018This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine... (Comparative Study)
Comparative Study Review
This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine and amphotericin B (AMB), including their absorption, distribution, metabolism and excretion and potential drug-drug interactions. This overview provides an understanding of their clinical pharmacokinetics, which could assist in rationalising and optimising treatment regimens, especially in combining multiple antileishmanial drugs in an attempt to increase efficacy and shorten treatment duration. Pentavalent antimony pharmacokinetics are characterised by rapid renal excretion of unchanged drug and a long terminal half-life, potentially due to intracellular conversion to trivalent antimony. Pentamidine is the only antileishmanial drug metabolised by cytochrome P450 enzymes. Paromomycin is excreted by the kidneys unchanged and is eliminated fastest of all antileishmanial drugs. Miltefosine pharmacokinetics are characterized by a long terminal half-life and extensive accumulation during treatment. AMB pharmacokinetics differ per drug formulation, with a fast renal and faecal excretion of AMB deoxylate but a much slower clearance of liposomal AMB resulting in an approximately ten-fold higher exposure. AMB and pentamidine pharmacokinetics have never been evaluated in leishmaniasis patients. Studies linking exposure to effect would be required to define target exposure levels in dose optimisation but have only been performed for miltefosine. Limited research has been conducted on exposure at the drug's site of action, such as skin exposure in cutaneous leishmaniasis patients after systemic administration. Pharmacokinetic data on special patient populations such as HIV co-infected patients are mostly lacking. More research in these areas will help improve clinical outcomes by informed dosing and combination of drugs.
Topics: Animals; Antiprotozoal Agents; Coinfection; Drug Interactions; HIV Infections; Half-Life; Humans; Leishmaniasis
PubMed: 28756612
DOI: 10.1007/s40262-017-0570-0