trifloxystrobin and difenoconazole

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1 μM was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxystrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25-2.5 μM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10 μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. Toxicity analysis revealed that MMV021013 showed high selectivity indices (SI ≥ 10) against the fungi tested. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.

Topics: Acetates; Antifungal Agents; Ascomycota; Auranofin; Biphenyl Compounds; Chromoblastomycosis; Dioxolanes; Drug Synergism; Exophiala; Fungi; Humans; Imines; Iodoquinol; Pyrimidines; Strobilurins; Triazoles

Late wilt, a disease severely affecting maize fields throughout Israel, is characterized by relatively rapid wilting of maize plants before tasseling and until shortly before maturity. The disease's causal agent is the fungus Harpophora maydis, a soil-borne and seed-borne pathogen, which is currently controlled using reduced sensitivity maize cultivars. In a former study, we showed that Azoxystrobin (AS) injected into a drip irrigation line assigned for each row can suppress H. maydis in the field and that AS seed coating can provide an additional layer of protection. In the present study, we examine a more cost-effective protective treatment using this fungicide with Difenoconazole mixture (AS+DC), or Fluazinam, or Fluopyram and Trifloxystrobin mixture, or Prothioconazole and Tebuconazole mixture in combined treatment of seed coating and a drip irrigation line for two coupling rows. A recently developed Real-Time PCR method revealed that protecting the plants using AS+DC seed coating alone managed to delay pathogen DNA spread in the maize tissues, in the early stages of the growth season (up to the age of 50 days from sowing), but was less effective in protecting the crops later. AS+DC seed coating combined with drip irrigation using AS+DC was the most successful treatment, and in the double-row cultivation, it reduced fungal DNA in the host tissues to near zero levels. This treatment minimized the development of wilt symptoms by 41% and recovered cob yield by a factor of 1.6 (to the level common in healthy fields). Moreover, the yield classified as A class (cob weight of more than 250 g) increased from 58% to 75% in this treatment. This successful treatment against H. maydis in Israel can now be applied in vast areas to protect sensitive maize cultivars against maize late wilt disease.

Topics: Acetates; Antifungal Agents; Ascomycota; Benzamides; Dioxolanes; Imines; Plant Diseases; Pyridines; Strobilurins; Triazoles; Zea mays

An optimized quick, easy, cheap, effective, rugged and safe method for the simultaneous determination of difenoconazole, trifloxystrobin and its metabolite trifloxystrobin acid residues in watermelon and soil was developed and validated by gas chromatography with tandem mass spectrometry. The samples were extracted with acetonitrile (1% formic acid) and cleaned up by dispersive solid-phase extraction with octadecylsilane sorbent. The limit of quantification of the method was 0.01 mg/kg, and the limit of detection was 0.003 mg/kg for all three analytes. The recoveries of the fungicides in watermelon, pulp and soil were 72.32-99.20% for difenoconazole, 74.68-87.72% for trifloxystrobin and 78.59-92.66% for trifloxystrobin acid with relative standard deviations of 1.34-14.04%. The dissipation dynamics of difenoconazole and trifloxystrobin in watermelon and soil followed the first-order kinetics with half-lives of 3.2-8.8 days in both locations. The final residue levels of difenoconazole and trifloxystrobin were below 0.1 mg/kg (maximum residue level [MRL] set by China) and 0.2 mg/kg (MRL set by European Union), respectively, in pulp samples collected 14 days after the last application. These results could help Chinese authorities to establish MRL of trifloxystrobin in watermelon and provide guidance for the safe and proper application of both fungicides on watermelon.

Topics: Acetates; Citrullus; Dioxolanes; Fungicides, Industrial; Gas Chromatography-Mass Spectrometry; Imines; Limit of Detection; Linear Models; Methacrylates; Pesticide Residues; Reproducibility of Results; Strobilurins; Triazoles

Calonectria (formerly Cylindrocladium) infection of pot azalea (Rhododendron simsii Planch) is an important disease problem in which usually one or two of the four plants per pot show progressing leaf and especially stem lesions, leading to mortality of the respective plant and rendering the pot unmarketable. This may occur in a later stage of the growing season, leading to significant commercial losses. The main objective of this study was to test a range of fungicides for their efficacy against this pathogen. To test the fungicides, a bioassay was first developed in which mycelium and conidiospores of the pathogen were produced on Potato Dextrose Agar, blended in water, and dilutions of the resulting suspension inoculated at the base of 11-week-old cuttings three weeks after they had been trimmed. Disease progression was monitored up to 7 weeks post inoculation and a disease index on a scale of 0 to 3 was established. In the actual efficacy trial, the following fungicides (with corresponding active ingredient(s)) were tested as preventive treatments: Topsin M 70 WG (thiophanate-methyl), Sporgon (prochloraz), Signum (boscalid+pyraclostrobin), Switch (cyprodinyl+fludioxonil), Flint 50WG (trifloxystrobin), Ortiva Top (azoxystrobin+difenoconazole) and Fungaflor (imazalil). Disease expression started after about 2 weeks, increased approximately 1 index level, and leveled off 5 weeks after inoculation. The best control was observed with Sporgon, Ortiva Top and Signum. Switch produced intermediate effects and insufficient control was observed with Topsin, Flint and Fungaflor. These results explain why specific standard fungicide treatments, such as those with Topsin, fail to control the disease, while they can be effective against a different Calonectria species such as C. pseudonaviculata, the cause of boxwood blight.

Topics: Acetates; Carbamates; Dioxolanes; Fungicides, Industrial; Hypocreales; Imidazoles; Imines; Methacrylates; Plant Diseases; Pyrazoles; Pyrimidines; Rhododendron; Strobilurins; Triazoles