Cell wall biosynthesis/assembly. [3]
Androgen receptor (AR) antagonist. [2]

Dimethomorph has EC50s of less than 0.1 µg/mL, 0.14 µg/mL, and 0.38 µg/mL for Phytophthora capsici, P. citrophthora, and P. parasitica, respectively, inhibiting these oomycetes [1]. Although dimethomorph does not reduce AR activity in a yeast anti-androgen screen (IC50s = 0.263 and 38.5 µM), it does so in a reporter assay on MDA-kb2 human breast cancer cells [2].

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For Phytophthora capsici, P. citrophthora, and P. parasitica:- Mycelial growth: EC50 values ranged from <0.1 to 0.38 µg/ml. EC90 values ranged from 0.32 to 1.6 µg/ml. At 1 µg/ml, reduction of mycelial growth was significantly greater than for azoxystrobin, fluazinam, fosetyl-Al, and metalaxyl. [1]- Sporangium formation: EC50 values were <1.0 µg/ml for all three species. EC90 values were <1.0 µg/ml for all three species. Reduction at 1 µg/ml was significantly greater than for azoxystrobin, fluazinam, and fosetyl-Al. Sporangia formation by P. capsici and P. citrophthora was totally suppressed at 1.0 µg/ml. For P. parasitica, sporulation was completely arrested at 10 µg/ml. [1]- Zoospore motility: EC50 values for P. capsici, P. citrophthora, and P. parasitica were 24.0, 12.0, and 6.8 µg/ml, respectively. EC90 values were 139, 105, and 72 µg/ml, respectively. [1]- Zoospore cyst germination: EC50 values for P. capsici, P. citrophthora, and P. parasitica were 3.9, 3.3, and 7.2 µg/ml, respectively. EC90 values were 21.0, 5.6, and 21.0 µg/ml, respectively. Inhibition at 10 µg/ml was significantly higher than for azoxystrobin, fluazinam, fosetyl-Al, and metalaxyl. Complete inhibition was achieved with 100 µg/ml. [1]
For Phytophthora infestans:- Cystospore germination: Technical grade ED50 was 0.037 µg/ml. Formulated product ED50 was 0.002 µg/ml. MIC (complete inhibition) was 0.5 µg/ml. [3]- Sporangial germination: Technical grade ED50 was 0.0414 µg/ml. Formulated product ED50 was 0.0414 µg/ml. [3]- Mycelial growth: Technical grade ED50 for radial growth on solid medium was 0.077 µg/ml, with growth stopping at 0.5 µg/ml. For mycelial fresh weight in liquid culture, the dose for 50% inhibition was not specified but was higher than for MPD. [3]- Infection prevention on detached potato leaves: Formulated product ED50 was 0.082 µg/ml, with complete inhibition at 0.05 µg/ml. [3]- Infection prevention on intact potato plants: Formulated product ED50 was 0.44 µg/ml, with complete control at 25 µg/ml. On intact tomato plants, ED50 was 3.11 µg/ml, with complete control at 25 µg/ml. [3]- Post-infection activity (curative): When applied 24 hours post-inoculation (hpi) on potato, 10 µg/ml inhibited sporulation by 70% (ED50 not provided). On tomato, 1-10 µg/ml was significantly more effective than on potato, with 10 µg/ml inhibiting sporulation by 96%. Curative efficacy was lost if applied 48 hpi. [3]- Sporulation inhibition on detached tomato leaves: Formulated product ED50 was 3.7 µg/ml. In another assay, a droplet application of formulated product at 100 µg/ml reduced sporangia yield by 76% compared to the water control. [3]- Trans-laminar activity: Formulated product ED50 on intact potato plants was 358 µg/ml; on intact tomato plants it was 111 µg/ml. [3]
Antiandrogenic Activity:- In the MDA-kb2 assay (human breast cancer cell line with AR-luciferase reporter), Dimethomorph exhibited antiandrogenic activity with an IC20 of 0.263 µM. No cytotoxicity was observed at tested concentrations (EC20 > 50 µM). No androgenic activity was detected. [2]- In the Yeast Antiandrogen Screen (YAS), the IC20 was 38.5 µM. [2]

For Phytophthora infestans in potato shade house trials:- At a dose of 150 g a.i./ha, Dimethomorph was significantly more effective than iprovalicarb but less effective than mandipropamid in controlling late blight epidemics, based on the Area Under the Disease Progress Curve (AUDPC). [3]- At a dose of 300 g a.i./ha, its efficacy was not significantly different from mandipropamid but was still more effective than iprovalicarb. [3]- The calculated dose required to inhibit AUDPC by 50% (ED50) was 73.6 g/ha (mean of two years of data). [3]- In a separate single-application trial at 150 g/ha, 30 days post-inoculation (dpi), the number of infected leaflets per 10m row was 175 ± 50. At 39 dpi, it was 725 ± 126. [3]

Antiandrogenicity assay (MDA-kb2): MDA-kb2 cells (human breast cancer cells stably transfected with a firefly luciferase reporter gene driven by an androgen-response element-containing promoter) were seeded at 1x10^5 cells/mL in phenol red-free medium. After 24 hours, cells were exposed to eight serial dilutions of Dimethomorph with or without 0.25 nM dihydrotestosterone (DHT). Following a 24-hour incubation, luciferase activity was determined. Luminescence was normalized to DHT alone (100% maximum response) and solvent-only controls (0% minimum response). The concentration that inhibits the androgenicity of DHT by 20% (IC20) was calculated from the concentration-response curve. [2]
Antiandrogenicity assay (YAS): The Yeast Antiandrogen Screen (YAS) uses yeast transfected with the human androgen receptor. Stimulation of the AR causes a color change in the media, measured by absorbance at 540nm. Cells were coincubated with Dimethomorph and 6.4 nM DHT for 53 hours at 28°C. Turbidity was measured at 620nm to check for cytotoxicity. The pesticide concentration range was based on potency observed in the MDA-kb2 assay. [2]

Shade house trial for late blight control in potato (2 experiments): Potato plants (cv. Dita or Nicola) were treated with formulated Dimethomorph at doses of 75, 150, or 300 g a.i./ha using a motorized backpack sprayer. Eight hours after the first spray, plants were spray-inoculated with a sporangial suspension (1,000 sporangia/ml) of a mixed P. infestans isolate population. After inoculation, plants were covered with plastic sheets overnight to ensure infection. Sprays were repeated at 7- to 8-day intervals for a total of four applications. The number of infected leaflets per row was counted at 3- to 5-day intervals over 44 to 57 days. The area under the disease progress curve (AUDPC) was calculated to assess fungicide efficacy. [3]

Absorption, Distribution and Excretion
Following oral administration of dimethomorphine to rats (single dose 10 mg/kg; repeated administration of 10 mg/kg for 14 days; repeated administration of 10 mg/kg for 7 days; single dose 500 mg/kg), the drug was rapidly excreted in urine and feces. In all dosing regimens, the majority (80-90%) of the radiolabeled material was excreted in feces. A small amount (6-16%) was excreted in urine, while only trace amounts (0.1-0.4%) were detected in organs and tissues. The rapid excretion of metabolites in urine and bile indicates rapid drug absorption. After a single high-dose administration (500 mg/kg), a large amount (50%) of the radioactive material in the feces bound to the parent compound, indicating that absorption had reached saturation. Regardless of whether the treatment was low or high dose, urinary excretion was often higher in female rats than in male rats (up to 2 times in the low-dose group). The retention rate of dimethmorphine or radioactive substances derived from 14C-dimethmorphine in most tissues is typically 1%, but the retention rate in the liver is slightly higher (1.4%), while the higher retention rate in gastrointestinal organs is attributed to radioactivity in the luminal contents. Metabolites/Metabolites: Following oral administration of dimethmorphine to rats (single dose 10 mg/kg; repeated doses over 14 days; repeated doses over 7 days; single dose 500 mg/kg), the drug is rapidly excreted in urine and feces. …Urinary metabolites originate from the demethylation of the dimethoxybenzene ring and the oxidation of the morpholine ring. After low-dose treatment, bile metabolites account for the majority of fecal excretion. The main bile metabolite is one (or possibly two) glucuronide from the demethylation of the dimethoxybenzene ring. This report presents the metabolic pathway of dimethmorphine. In rats, the primary metabolic pathway is demethylation of the dimethoxy group or oxidation of the CH2 group (ortho- or meta-) on the morphine ring.
Biological Half-Life
Following oral administration of dimethmorphine to rats (10 mg/kg single dose; 10 mg/kg repeated doses over 14 days; 10 mg/kg repeated doses over 7 days; 500 mg/kg single dose), the drug is rapidly excreted in urine and feces. Bile excretion exhibits first-order kinetics, with a half-life of approximately 3 hours for low doses (10 mg/kg) and approximately 11 hours for males and approximately 6 hours for females for high doses (500 mg/kg).

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In the MDA-kb2 cell assay, Dimethomorph showed no cytotoxicity up to the highest concentration tested, with an EC20 for cytotoxicity > 50 µM. [2]

[1]. Impact of Azoxystrobin, Dimethomorph, Fluazinam, Fosetyl-Al, and Metalaxyl on Growth, Sporulation, and Zoospore Cyst Germination of Three Phytophthora spp. Plant Dis. 2000 Apr;84(4):454-458.

[2]. Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens. Environ Health Perspect. 2011 Jun;119(6):794-800.

[3]. Differential Activity of Carboxylic Acid Amide Fungicides Against Various Developmental Stages of Phytophthora infestans. Phytopathology. 2007 Oct;97(10):1274-83.

Dimethylmorpholine is a mixture of (E)-dimethylmorpholine and (Z)-dimethylmorpholine, with no specific ratio specified. It is a systemic fungicide used on grapevines, potatoes, and greenhouse crops; only the Z isomer has fungicidal activity. It is both an exogenous substance and an environmental pollutant and antifungal pesticide. It is a mixture and a morpholine fungicide. It contains (E)-dimethylmorpholine and (Z)-dimethylmorpholine. Mechanism of Action: A systemic fungicide with good protective, curative, and antispore activities. Inhibits oomycete cell wall formation. Only the Z isomer itself is active, but because the isomers rapidly interconvert under light, it is not more advantageous than the E isomer in practical applications.

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Dimethomorph is a Carboxylic Acid Amide (CAA) fungicide. It belongs to FRAC group 40 and is known to be at high risk for resistance development. All CAA fungicides, including dimethomorph, belong to one cross-resistance group. [3]
At the biochemical level, its mode of action is associated with cell wall biogenesis. [1]
It is used to control diseases caused by Phytophthora spp., such as crown and root rot of pepper and gummosis and root rot of citrus. [1] In Europe, its authorization for use was set to expire in September 2017 (as of the 2011 publication). [2]
The Dimethomorph technical grade material used in one study had a molecular weight of 266. [3]

C21H22CLNO4

387.86

387.123

110488-70-5

Dimethomorph-d8;1346606-71-0

5889665

White to off-white solid powder

1.2±0.1 g/cm3

584.9±50.0 °C at 760 mmHg

125-149ºC

307.5±30.1 °C

0.0±1.6 mmHg at 25°C

1.581

3.71

0

4

5

27

512

0

COC1=C(C=C(C=C1)/C(=C/C(=O)N2CCOCC2)/C3=CC=C(C=C3)Cl)OC

QNBTYORWCCMPQP-NBVRZTHBSA-N

InChI=1S/C21H22ClNO4/c1-25-19-8-5-16(13-20(19)26-2)18(15-3-6-17(22)7-4-15)14-21(24)23-9-11-27-12-10-23/h3-8,13-14H,9-12H2,1-2H3/b18-14+

(E)-3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-1-morpholin-4-ylprop-2-en-1-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 6.67 mg/mL (17.20 mM)

Solubility in Formulation 1: ≥ 0.67 mg/mL (1.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 0.67 mg/mL (1.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)