Compounds for use as inhibitors of alternative oxidase or cytochrome bc1 complex
A technology of alternating oxidase and cytochrome, which is applied in the field of alternating oxidase and can solve the problems of increased expression of alternating oxidase
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0150] Example 1: Characterization of Alternate Oxidase (AOX) Binding Pocket
[0151] The major breakthrough of this study is the first determination of the crystal structure of the alternative oxidase (AOX) protein in the presence and absence of stoichiometric inhibitors, such as figure 2 shown. The inventors found that the pocket does not change, ie it is essentially the same in the presence or absence of inhibitors. Knowing the crystal structure of AOX in the presence of inhibitors greatly facilitated the inventors for certain rational fungicidal molecular designs, as discussed below, leading to the generation of libraries of AOX inhibitor compounds that have the potential to act as specific targets for AOX The ability of phytopathogenic fungicides.
[0152] Correspondingly, once the inventor generates such figure 2 Shown in the crystal structure of AOX, they proceeded to characterize the quinone-binding pocket of AOX in detail using site-directed mutagenesis. see ...
Embodiment 2
[0156] Embodiment 2: Design and synthesis of AOX inhibitors
[0157] The inventor designed and synthesized multiple AOX inhibitors based on the compound ascofuranone, the chemical structure of which is as follows: Figure 5 shown. Ascofuranone has a complex synthetic pathway and has an active aldehyde group (-CHO). Several ascofuranone derivatives, Colletochlorin B ( Figure 5 Marker structure "2" in, where R is CHO), Figure 5 Shown compound "3", wherein R is CH 2 OH, and 4a-4h, where R is as Figure 5 shown.
[0158] The inhibitory effects of some of these compounds were evaluated and the results are summarized in Table 1.
[0159] Table 1: Inhibitory effect on recombinant AOX protein
[0160] Inhibitor
IC50
Ascofuranone
58pM
Colletochlorin B
165pM
Octyl gallate
105nM
Salicylhydroxamic Acid (SHAM)
7μM
[0161] Table 1 summarizes the concentrations of inhibitors required to reduce the respiration of p...
Embodiment 3
[0163] Embodiment 3: the synthesis of Colletochlorin B
[0164] The chemical structure of Colletochlorin B is as Figure 6 As shown, the method used for its synthesis is as Figure 7 shown.
[0165] Step 1: Compound (1) to Compound (2)
[0166] orcinol (5g, 40mmol) and Zn(CN) 2 (7.1g, 60mmol) was placed in a three-necked flask, under N 2Under mechanical stirring. 50 mL of ether was added and the reaction was saturated with HCl gas. After 2 hours, the ether was decanted off and 50 mL of water was added to the reaction mixture. When heated to 100°C, the product precipitated out of the solution. The crude product was collected by Buchner filtration and recrystallized from water to give the aldehyde (4.6 g) in 76% yield.
[0167] Step 2: Compound (2) to Compound (3)
[0168] Licandiphenol aldehyde (527mg, 3.5mmol) was placed in N 2 , and dissolved in anhydrous ether (60ml) on an ice bath. SO 2 Cl 2 (1.35ml, 4.7mmol) was diluted in diethyl ether (15ml) and added ...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More