Biological Features and Molecular Genetic Structure of Habrobracon hebetor Populations

One of the promising entomophages capable of controlling the abundance of the codling moth is Habrobracon hebetor Say. Natural populations of the gabrobragon can reduce the number of caterpillars of the corn moth to 22%, the garden moth to 35%, the cotton moth to 45%, and the gamma moth to 30%. This work aims to assess the parasitic activity of the gabrobragon as a regulator of the codling moth abundance in various geographic populations, to select a host insect for its mass breeding in laboratory conditions, and to assess the molecular genetic variability of the structure of H. hebetor populations. The capture of natural populations of the gabrobragon H. hebetor was carried out in apple orchards in Krasnodar Krai and Stavropol Krai of Russia using cassettes in which caterpillars of the codling moth were placed. As a result of the research, the natural starting population of the gabrobragon H. hebetor was captured, and a method for their maintenance and breeding was developed. The most effective host insect is the wax moth (Galleria mellonela L.), which resulted in 195 adults, compared to 98 of the mill moth (Ephestia kuhniella Zell.). The gabrobragon population introduced into the apple tree cenosis continued its reproduction in natural conditions and largely suppressed the number and harmfulness of the codling moth. The RAPD analysis of the Krasnodar and Stavropol populations of Habrobracon hebetor Say revealed a high level of DNA polymorphism and genetic diversity in the studied geographic populations of the gabrobragon. At the same time, intrapopulation variability was 87.1%, while interpopulation variability accounted for 12.9% of the total indicator. The limited gene flow (Nm = 3.298) results in relatively low identity (GI = 0.906) between populations and significant interpopulation variability. This indicates that the analyzed insect samples probably represent different geographic populations of the H. hebetor ectoparasite.

Article Review: Cordia myxa L.: The Gift of the Nature, A Review

Cordia myxa L. is one of the medical plants that plays an important role in the treatment of many diseases. There are many studies explained that C. myxa can show anti-inflammatory, anti-diabetic, antiparasitic, antimicrobial and immunomodulatory properties. This review was focused on the active compounds and medical effects of C. myxa. The fatty acids contents are particularly high (9.9%). Sodium and potassium constitute the largest mineral proportion (13 ppm and 29 ppm respectively) of the fruit. However, the toxic heavy metals such as lead, cadmium, chromium and copper have not been found in the fruit. This gives an additional significant benefit of the medical uses of the plant. The content of alkaloids, saponin, polyphenols, and comarine were recorded and was relatively high compared to steroids, resins, glycosides, tannins, and gum that found to be in less amounts. When the mucilage was extracted, the alkaloids constitute more than 35%. By using the Folin‐Ciocalteu, C. myxa extracts have a high Phenolic content. The antibacterial activity against gram-negative bacteria were included in the fruit mucilage extract while the alcoholic extracts have no effect on all bacterial isolates. In addition, the mucilage extract showed anti-parasitic activity when it was tested against Leishmania infantum promastigotes. However, the highest concentration of extract significantly reduced the amounts of lymphocytes. Moreover, ethanolic extracts of C. myxa fruits give rise to leucocyte and lymphocyte count. Future research needs to be done on this kind of herbs which could show high medicinal activity.

Evaluation of Origanum vulgare Essential Oil and Its Active Ingredients as Potential Drugs for the Treatment of Toxoplasmosis

Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was firstly studied, and then, carvanol (Ca), the main ingredient of Ov EO was evaluated using the MTT assay on human foreskin fibroblast (HFF) cells in vitro. The cytotoxicity was evaluated using the MTT assay on HFF cells. The CC50 of Ov EO and Ca was 134.9 and 43.93 μg/ml, respectively. Both of them exhibited anti-parasitic activity, and inhibited the growth of T. gondii in a dose-dependent manner. For the inhibition effect, Ca was better than Ov EO at the same concentration, the IC50 of Ov EO and Ca was 16.08 and 7.688 μg/ml, respectively. In addition, treatment with Ca, was found to change the morphology of T. gondii tachyzoites and made their shapes curl up. These results showed that Ca was able to inhibit the proliferation of T. gondii by reducing invasion, which may be due to its detrimental effect on the mobility of tachyzoites. Our results indicated that Ca could be a potential new and effective drug for treating toxoplasmosis.

COELENTERATE TOXINS, ITS PHARMACEUTICAL AND THERAPEUTIC EFFECTS

Present review article emphasizes species specific coelenterate toxins, its pharmaceutical and therapeutic effects. Most of the coelenterates inflict venom accidently by using nematocysts found on arms. These animals very quickly do massive and multiple inflictions of venom which causes cardiotoxicity that leads to the death of human beings. Coelenterate venom toxin groups differ in their composition and show diverse biological activity i.e. cytolytic or neurotoxic, hemolytic, anti-parasitic activity, α-amylase inhibitor activity, and analgesic activity anti-cancerous and antitumor activity, anti-inflammatory and antimicrobial activity. Coelenterate venom initiates toxic and immunological reactions exert their effects by modifying the properties of the ion channels involved in action potential generation in nerve, heart, and skeletal muscles. This article suggests available information, on coelenterate toxins could be used to develop potential therapeutic interventions for various human diseases and disorders.

Overcoming the Prokaryote/Eukaryote Barrier in Tuberculosis Treatment: A Prospect for the Repurposing and Use of Antiparasitic Drugs

Antimicrobial resistance, the so-called silent pandemic, is pushing industry and academia to find novel antimicrobial agents with new mechanisms of action in order to be active against susceptible and drug-resistant microorganisms. In the case of tuberculosis, the need of novel anti-tuberculosis drugs is specially challenging because of the intricate biology of its causative agent, Mycobacterium tuberculosis. The repurposing of medicines has arisen in recent years as a fast, low-cost, and efficient strategy to identify novel biomedical applications for already approved drugs. This review is focused on anti-parasitic drugs that have additionally demonstrated certain levels of anti-tuberculosis activity; along with this, natural products with a dual activity against parasites and against M. tuberculosis are discussed. A few clinical trials have tested antiparasitic drugs in tuberculosis patients, and have revealed effective dose and toxicity issues, which is consistent with the natural differences between tuberculosis and parasitic infections. However, through medicinal chemistry approaches, derivatives of drugs with anti-parasitic activity have become successful drugs for use in tuberculosis therapy. In summary, even when the repurposing of anti-parasitic drugs for tuberculosis treatment does not seem to be an easy job, it deserves attention as a potential contributor to fuel the anti-tuberculosis drug pipeline.

Discovery of imidazole-based inhibitors of P. falciparum cGMP-dependent protein kinase

The discovery of new targets for treatment of malaria and in particular those aimed at the pre-erythrocytic stage in the life cycle, advanced with the demonstration that orally administered inhibitors of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) could clear infection in a murine model. This enthusiasm was tempered by unsatisfactory safety and/or pharmacokinetic issues found with these chemotypes. To address the urgent need for new scaffolds, this manuscript presents initial structure-activity relationships in an imidazole scaffold at four positions, representative in vitro ADME, hERG characterization and cell-based anti-parasitic activity. This series of PfPKG inhibitors has good in vitro PfPKG poten-cy, low hERG activity and cell-based anti-parasitic activity against multiple Plasmodium species that appears to correlate with in vitro potency.

In Vitro Anti-Trypanosoma cruzi Activity of Halophytes from Southern Portugal Reloaded: A Special Focus on Sea Fennel (Crithmum maritimum L.)

Marine halophytes are an outstanding reservoir of natural products and several species have anti-infectious traditional uses. However, reports about their potential use against neglected tropical ailments, such as Chagas disease, are scarce. This work evaluated for the first time the in vitro anti-Trypanosoma cruzi activity of extracts from the aromatic and medicinal species Helichrysum italicum subsp. picardii (Boiss. & Reut.) Franco (Asteraceae, everlasting) and Crithmum maritimum L. (Apiaceae, sea fennel). For that purpose, decoctions, tinctures, and essential oils from everlasting’s flowers and sea fennel’s stems, leaves, and flowers were tested against intracellular amastigotes of two T. cruzi strains. The extract from the sea fennel flower decoction displayed significant anti-trypanosomal activity and no toxicity towards the host cell (EC50 = 17.7 µg/mL, selectivity index > 5.65). Subsequent fractionation of this extract afforded 5 fractions that were re-tested in the same model of anti-parasitic activity. Fraction 1 was the most active and selective (EC50 = 0.47 μg/mL, selectivity index = 59.6) and was submitted to preparative thin-layer chromatography. One major compound was identified, falcarindiol, which was likely the one responsible for the observed anti-trypanosomal activity. This was confirmed using a commercially sourced molecule. Target-fishing studies showed falcarindiol as a ligand of T. cruzi spermidine synthase, pointing to a potential enzyme-inhibiting anti-trypanosomal mechanism of action. Overall, this work shows that sea fennel can provide effective anti-parasitic molecule(s) with potential pharmacological applications in the treatment of CD.

Maca against Echinococcosis?—A Reverse Approach from Patient to In Vitro Testing

Drug-based treatment of alveolar echinococcosis (AE) with benzimidazoles is in most cases non-curative, thus has to be taken lifelong. Here, we report on a 56-year-old male AE patient who received standard benzimidazole treatment and biliary plastic stents, and additionally self-medicated himself with the Peruvian plant extract Maca (Lepidium meyenii). After 42 months, viable parasite tissue had disappeared. Based on this striking observation, the anti-echinococcal activity of Maca was investigated in vitro and in mice experimentally infected with Echinococcus multilocularis metacestodes. Albendazole (ABZ)-treated mice and mice treated with an ABZ+Maca combination exhibited a significantly reduced parasite burden compared to untreated or Maca-treated mice. As shown by a newly established UHPLC-MS/MS-based measurement of ABZ-metabolites, the presence of Maca during the treatment did not alter ABZ plasma levels. In vitro assays corroborated these findings, as exposure to Maca had no notable effect on E. multilocularis metacestodes, and in cultures of germinal layer cells, possibly unspecific, cytotoxic effects of Maca were observed. However, in the combined treatments, Maca inhibited the activity of ABZ in vitro. While Maca had no direct anti-parasitic activity, it induced in vitro proliferation of murine spleen cells, suggesting that immunomodulatory properties could have contributed to the curative effect seen in the patient.

Discovery of novel potent, cell-permeable inhibitors of P. falciparum cGMP-dependent protein kinase.

The discovery of new targets for treatment of malaria advanced with the demonstration that orally administered inhibitors of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) could clear infection in a murine model. This enthusi-asm was tempered by unsatisfactory safety and/or pharmacokinetic issues found with these chemotypes. To address the urgent need for new scaffolds, we recently reported the discovery and optimization of novel, potent isoxazole-based PfPKG inhibitors that lacked any obvious safety warnings. This manuscript presents representative in vitro ADME, hERG charac-terization and cell-based antiparasitic activity of these PfPKG inhibitors. We also report the discovery and structure-activity relationships of a new series with good potency, low hERG activity and cell-based anti-parasitic activity comparable to a literature standard.

Synthesis of New Hybrid Derivatives from Metronidazole and Eugenol Analogues as Trypanocidal Agents

Background: The search for new drug compounds is always challenging and there are several different strategies that involve the most varied and creative approaches in medicinal chemistry. One of them is the technique of molecular hybridisation: forming a hybrid compound from two or more pharmacophoric subunits. These hybrids may maintain the characteristics of the original compound and preferably show improvements to its pharmacological action, with reduced side effects and lower toxicity when compared to the original components. This study specifically focuses on synthesising hybrid molecules which demonstrate trypanocidal activity against the epimastigote and trypomastigote forms of Trypanosoma cruzi. Methods: In this context, this study centres on the synthesis of a novel structural scaffold via molecular hybridisation; by using a triazole species to link a metronidazole unit to a eugenol analogue unit, the objective being to combine their therapeutic properties into a new molecular structure. The resulting hybrid molecules were evaluated against T. cruzi which is responsible for high incidences of trypanosomiasis in tropical countries such as Brazil. Results: The results of this study showed an improvement in the anti-parasitic activity of the hybrid compounds with the best result coming from hybrid compounds [8] and [9], which present an activity similar to the control drug benznidazole. The new compounds, utilising a triazole species as a coupling connector, demonstrated promising results and has highlighted the path for planning similar structural patterns to investigate new compounds. Conclusions: In summary, we can conclude that the synthesised hybrid compounds demonstrate that using a triazole to link metronidazole with natural phenols, produces hybrid molecules that are promising as a new class of compounds of therapeutic interest for further investigation.