New ventures in the chemistry of avermectins

Pitterna, Thomas; Cassayre, Jérôme; Hüter, Ottmar; Jung, Pierre M. J.; Maienfisch, Peter; Kessabi, Fiona Murphy; Quaranta, Laura; Tobler, Hans

doi:10.1016/j.bmc.2008.12.069

Cited by 109 publications

(64 citation statements)

References 17 publications

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“…Avermectins are a series 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties (Pitterna et al 2009). In recent years in Poland, as in other countries, avermectins are the most widely used drugs as they provide effective protection against the main groups of nematode parasites affecting horses (Lanusse et al 2009), high degree of safety and slow development of parasitic resistance.…”

Section: Introductionmentioning

confidence: 99%

A comparison of the efficacy and pharmacokinetics of ivermectin after spring and autumn treatments against Cyathostominae in horses

Sokół¹,

Raś-Noryńska²,

Michalczyk³

et al. 2015

Polish Journal of Veterinary Sciences

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The aim of the present study was to determine the efficacy of ivermectin against Cyathostominae infections and to describe the drug's pharmacokinetic parameters during two seasonal deworming treatments in horses. The study was performed on warm-blooded mares aged 3-12 years weighing 450-550 kg. A single bolus of an oral paste formulation of ivermectin was administered at a dose of 0.2 mg/kg BW in spring and autumn. Fecal samples were tested before treatment and 1, 2, 3, 4, 6, 10, 20, 30, 40, 50, 60, 75 days after treatment. Ivermectin concentrations in blood samples collected before treatment, 0.5, 1, 2, 3, 4, 6, 12, 24, 36 and 48 hours after treatment, and 3, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 and 75 days after drug administration were determined by high pressure liquid chromatography. Drug absorption was significantly (p<0.05) slower (t max : 21.89±11.43 h) in autumn than in spring (t max : 9.78±8.97 h). Maximum concentrations (C max ) of ivermectin in the blood plasma of individual horses (8.40-43.08 ng/ml) were observed 2-24 h after drug administration during the spring treatment and 2-36 h (6.43-24.86 ng/ml) after administration during the autumn treatment. Significantly higher (p<0.05) ivermectin concentrations were found during the first 4 hours after administration in spring in comparison with those determined after the autumn treatment.The administration of the recommended dose of ivermectin resulted in 100% elimination of parasitic eggs from feces in spring and autumn treatment.

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Section: Introductionmentioning

confidence: 99%

A comparison of the efficacy and pharmacokinetics of ivermectin after spring and autumn treatments against Cyathostominae in horses

Sokół¹,

Raś-Noryńska²,

Michalczyk³

et al. 2015

Polish Journal of Veterinary Sciences

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“…It is primarily a stomach poison with some contact activity and is particularly toxic to Lepidoptera and Diptera. The avermectins are a series 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties generated as fermentation products by S. avermitilis (Pitterna et al, 2009). Cholesterol oxidase derived from Streptomyces broth has shown to have selective, high potency against cotton boll weevil, stunting effect in H. virescens, H. zea and Pectinophora gossypiella which might be due to disruption of the midgut epithelial membrane (Purcell et al, 1993).…”

Section: Actinomycetesmentioning

confidence: 99%

Microbes as interesting source of novel insecticides: A review

Kumari¹,

Vijayabharathi²,

Srinivas³

et al. 2014

Afr. J. Biotechnol.

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Microbes are ubiquitous, survive in all sorts of environments and have a profound influence on the earth. In the present day plant protection scenario, development of resistance to chemical pesticides is the major hurdle in insect pest management. In recent years, several microbes with potential insecticidal properties have come to light. Viruses, bacteria, fungi and protozoa that are known to produce an array of metabolites or toxins, form the basis for microbial insecticides. Since these versatile organisms are amenable for genetic engineering, strains with good insecticidal properties can be identified, evaluated and utilized for pest control. This paper reviews the insecticidal properties of microbes and their potential utility in pest management.

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“…A vermectins (AVMs) are a series of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties (1,2). Ivermectin (IVM), a hydrogenated product of AVM B1, has been one of the best-selling antiparasitics since 1981 (3).…”

mentioning

confidence: 99%

Gene Replacement for the Generation of Designed Novel Avermectin Derivatives with Enhanced Acaricidal and Nematicidal Activities

Huang

Chen²,

Zhang

et al. 2015

Appl Environ Microbiol

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c Avermectin (AVM) and ivermectin (IVM) are potent pesticides and acaricides which have been widely used during the past 30 years. As insect resistance to AVM and IVM is greatly increasing, alternatives are urgently needed. Here, we report two novel AVM derivatives, tenvermectin A (TVM A) and TVM B, which are considered a potential new generation of agricultural and veterinary drugs. The molecules of the TVMs were designed based on structure and pharmacological property comparisons among AVM, IVM, and milbemycin (MBM). To produce TVMs, a genetically engineered strain, MHJ1011, was constructed from Streptomyces avermitilis G8-17, an AVM industrial strain. In MHJ1011, the native aveA1 gene was seamlessly replaced with milA1 from Streptomyces hygroscopicus. The total titer of the two TVMs produced by MHJ1011 reached 3,400 mg/liter. Insecticidal tests proved that TVM had enhanced activities against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, as desired. This study provides a typical example of exploration for novel active compounds through a new method of polyketide synthase (PKS) reassembly for gene replacement. The results of the insecticidal tests may be of use in elucidating the structure-activity relationship of AVMs and MBMs.A vermectins (AVMs) are a series of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties (1, 2). Ivermectin (IVM), a hydrogenated product of AVM B1, has been one of the best-selling antiparasitics since 1981 (3). However, as insect resistance to AVM (4) and IVM (5-7) is on the rise, alternatives or new products with enhanced potency and expanded spectra of activity are urgently needed.Milbemycins (MBMs) are another group of 16-membered macrolides that share similar structures with AVMs. The insecticidal activity of milbemectin (a mixture of MBMs A3 and A4) against some parasites is higher than those of AVM and IVM, while the toxicity is significantly lower (8).The structural differences among AVM, IVM, and MBM are in C-25, C-22-23, and C-13 ( Fig. 1) (9). IVM differs from AVM in C-22-23 (the former has a saturated bond, whereas the latter has a double bond in that position), but its toxicity is lower than that of AVM (10), implying that the single bond in C-22-23 should be the better structure in terms of safety. The major structural difference between IVM and MBM is a bisoleandrosyloxy substituent attached at C-13 of IVM, whereas that position is unsubstituted in MBM. Also, there are different alkyl substituents at C-25: in IVM, the substituent can be isopropyl or secondary butyl, while in MBM, it can be methyl or ethyl. However, MBM is more potent against some parasites and is safer than IVM, suggesting that one or both of the moieties in C-25 and C-13 of MBM is (are) the better structure(s) in these ways than that (those) of IVM. Another conclusion is that the two oleandroses in C-13 are important to the antiparasitic activity of IVM, since their removal will reduce the activity significantly, about 30-fold (10). Based on the curr...

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New ventures in the chemistry of avermectins

Cited by 109 publications

References 17 publications

A comparison of the efficacy and pharmacokinetics of ivermectin after spring and autumn treatments against Cyathostominae in horses

A comparison of the efficacy and pharmacokinetics of ivermectin after spring and autumn treatments against Cyathostominae in horses

Microbes as interesting source of novel insecticides: A review

Gene Replacement for the Generation of Designed Novel Avermectin Derivatives with Enhanced Acaricidal and Nematicidal Activities

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