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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 -
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 -
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 -
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 -
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 -
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 -
Molecules (Basel, Switzerland) Mar 2022Species of the genus are used in traditional medicine against fever and malaria. The present study focuses on the isolation and identification of bioactive compounds...
Species of the genus are used in traditional medicine against fever and malaria. The present study focuses on the isolation and identification of bioactive compounds from extracts, and the evaluation of their antiprotozoal activity. Fractionation and isolation combined to LC-HRMS/MS-based dereplication provided 16 compounds: seven indole alkaloids, four indoline alkaloids, two secoiridoid glycosides, two iridoid glycosides, and one phenolic glucoside. One of the quaternary indole alkaloids () and one indoline alkaloid () have never been reported before. Their structures were elucidated by analysis of spectroscopic data, including 1D and 2D NMR experiments, UV, IR, and HRESIMS data. The absolute configurations were determined by comparison of the experimental and calculated ECD data. The extracts and isolated compounds were evaluated for their antiprotozoal activity towards , , , and as well as for their cytotoxicity against rat skeletal myoblast L6 cells. The dichloromethane/methanol (1:1) root extract showed strong activity against (IC value of 3.5 µg/mL). Among the compounds isolated, tubotaiwine () displayed the most significant antiplasmodial activity with an IC value of 8.5 µM and a selectivity index of 23.4. Therefore, extract can be considered as a source of indole alkaloids with antiplasmodial activity.
Topics: Animals; Antimalarials; Antiprotozoal Agents; Apocynaceae; Leishmania donovani; Malaria, Falciparum; Plant Extracts; Plasmodium falciparum; Rats; Trypanosoma brucei rhodesiense
PubMed: 35408605
DOI: 10.3390/molecules27072200 -
Molecules (Basel, Switzerland) Jan 2021Thiazole, a five-membered heteroaromatic ring, is an important scaffold of a large number of synthetic compounds. Its diverse pharmacological activity is reflected in... (Review)
Review
Thiazole, a five-membered heteroaromatic ring, is an important scaffold of a large number of synthetic compounds. Its diverse pharmacological activity is reflected in many clinically approved thiazole-containing molecules, with an extensive range of biological activities, such as antibacterial, antifungal, antiviral, antihelmintic, antitumor, and anti-inflammatory effects. Due to its significance in the field of medicinal chemistry, numerous biologically active thiazole and bisthiazole derivatives have been reported in the scientific literature. The current review provides an overview of different methods for the synthesis of thiazole and bisthiazole derivatives and describes various compounds bearing a thiazole and bisthiazole moiety possessing antibacterial, antifungal, antiprotozoal, and antitumor activity, encouraging further research on the discovery of thiazole-containing drugs.
Topics: Animals; Anti-Infective Agents; Antifungal Agents; Antineoplastic Agents; Antiprotozoal Agents; Humans; Thiazoles
PubMed: 33504100
DOI: 10.3390/molecules26030624 -
ChemistryOpen Oct 2021A series of 60 4-aminomethyl 5-aryl-3-substituted isoxazoles were synthesized by an efficient method and evaluated in vitro against Leishmania amazonensis and...
A series of 60 4-aminomethyl 5-aryl-3-substituted isoxazoles were synthesized by an efficient method and evaluated in vitro against Leishmania amazonensis and Trypanosoma cruzi, protozoa that cause the neglected tropical diseases leishmaniasis and Chagas disease, respectively. Thirteen compounds exhibited a selective index greater than 10. The series of 3-N-acylhydrazone isoxazole derivatives bearing the bithiophene core exhibited the best antiparasitic effects.
Topics: Antiprotozoal Agents; Humans; Isoxazoles; Leishmaniasis; Structure-Activity Relationship; Trypanosoma cruzi
PubMed: 34331350
DOI: 10.1002/open.202100141 -
The American Journal of Tropical... Mar 2016Leishmaniasis continues to pose a major public health problem worldwide. With new epidemics occurring in endemic areas and the spread of the disease to previously free... (Review)
Review
Leishmaniasis continues to pose a major public health problem worldwide. With new epidemics occurring in endemic areas and the spread of the disease to previously free areas because of migration, tourism, and military activities, there is a great need for the development of an effective vaccine. Leishmaniasis is a disease of the poor, occurring mostly in remote rural villages with poor housing and little or no access to modern health-care facilities. In endemic areas, diagnosis of any form of leishmaniasis puts a huge financial strain on an already meagre financial resource at both the individual and community levels. Most often families need to sell their assets (land and livestock) or take loans from informal financial outfits with heavy interest rates to pay for the diagnosis and treatment of leishmaniasis. Here, we discuss the disease with special emphasis on its socioeconomic impact on the affected individual and community. In addition, we highlight the reasons why continued research aimed at developing an effective Leishmania vaccine is necessary.
Topics: Antiprotozoal Agents; Developing Countries; Humans; Leishmaniasis; Leishmaniasis Vaccines; Poverty; Rural Population
PubMed: 26787156
DOI: 10.4269/ajtmh.15-0408