JPH1045747A - Antimycin-a group compound mixture - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antimycin-A group compound mixture that contains antimycins A5 and A6 in their total quantity of a half or more of the mixture and is useful for researches on physiological activity, etc. SOLUTION: This antimycin-A group compound mixture, which contains a plurality of compounds of antimycin A group, comprises at least one selected from a group consisting of antimycin A5 of formula I (R1 is sea-butyl or isobutyl), antimycin A6 of formula II (R2 is n-propyl or isopropyl) and their salts in their total quantity of 50mol% or more based on the whole quantity of the mixture, which is preferably obtained as a metabolic product produced by Streptomyces sp. POL-129 strains.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to antimycin A
With respect to the mixture of the compounds based on antimycin A,
Mixtures of ₅ and / or the antimycin A ₆ selectively number including antimycin A compound related.

[0002]

A series of compounds called antimycins A are known as effective antibiotics against certain fungi. It is also useful as a toxin for fish and is widely used to control the increase in fish. Furthermore, it has an electron transfer inhibiting action (Von Jagow.G. And
Liuk. TA (1986) Methods Enzymol. 126, 253-27
1) Therefore, it is frequently used to elucidate its mechanism of action, and is also known to have a K channel opening action (Iwamoto Takahiro (1991) Jpn. J. Pharmacol. 55,
(Suppl.1), 256).

[0003] As such an antimycin A-based compound, there are several kinds of compounds having a structure represented by the following general formula (A) and similar structures thereof. For example, assuming that the R moiety and / or the R ′ moiety in the general formula (A) are different from each other, antimycin A ₀ , A ₁ , A ₂ ,
Compounds such as A ₃ , A ₄ , A ₅ and A ₆ are known.

[0004]

Embedded image

[In the formula (A), R and R 'each represent a linear or branched alkyl group. ]

[0006] Among these series of related compounds, there are known compounds whose production method is known. However, antimycin A ₅ (8-ethyl-3) wherein R ₁ in the general formula (A) is an ethyl group is mentioned. -[[3- (formylamino) -2-hydroxybenzoyl] amino] -2,6-dimethyl-4,9-dioxo-1,5-dioxonan-7-yl-3- (or 2-) methylbutanoate ) And antimycin A
₆ (8-ethyl-3-[[3- (formylamino) -2
-Hydroxybenzoyl] amino] -2,6-dimethyl-4,9-dioxo-1,5-dioxonan-7-yl-n- (or iso) butanoic acid ester)
There is no single production method, and even if produced as a mixture, only a very small amount is obtained.

Further, antimycin A compound group, generally have been known to be produced by a number of actinomycetes, antimycin A ₅ and / or the antimycin A ₆
An actinomycete that efficiently produces as a main component has not been obtained, and thus its physiological activity is not known despite being expected.

[0008]

An object of the present invention is to provide a mixture of antimycin A compounds containing antimycin A ₅ , antimycin A ₆ or a physiologically acceptable salt thereof as a main component. And

[0009]

Means for Solving the Problems The present inventors have conducted intensive studies in view of such circumstances, and as a result, have found that the above problems can be solved by culturing a novel strain isolated from soil in Ibaraki Prefecture. Heading, completed the invention.

That is, the present invention relates to a mixture of antimycin A compounds containing a plurality of antimycin A compounds obtained as a metabolite of actinomycetes, wherein the mixture comprises an antimycin A compound represented by the following general formula (I): ₅ and at least one selected from the group consisting of antimycin A ₆ represented by the following general formula (II) and salts thereof in a total amount of 50 mol% or more based on the total amount of the mixture. A mixture of the following antimycin A compounds.

[0011]

Embedded image

[In the formula (I), R ₁ represents a sec-butyl group or an isobutyl group. In the formula (II), R ₂ is n
-Represents a propyl group or an isopropyl group. ]

[0013] The present invention also relates to the present invention, wherein the mixture of the antimycin A-based compound is Streptomyces sp. PO
It is intended to provide a mixture of the antimycin A-based compound obtained as a metabolite produced by L-129 strain (Streptomyces sp. POL-129).

Further, the present invention, the general formula (I) antimycin represented by A _5, or the general formula and salts thereof (I
And a antimycin A _6, or a salt thereof I), and their molar ratio, antimycin A _5, or a salt thereof: antimycin A _6, or a salt thereof = 90-50: 10
And a mixture of the antimycin A-based compounds of the formula:

[0015] The present invention also relates to Streptomyces sp. An object of the present invention is to provide a method for producing the mixture of antimycin A compounds, comprising a step of culturing POL-129 strain to produce the mixture of antimycin A compounds, and then purifying the culture solution.

The present invention also provides a pharmaceutical composition containing the mixture of the antimycin A compound as an active ingredient. Further, the present invention relates to Streptomyces sp. A metabolite produced by the POL-129 strain, the group consisting of antimycin A ₆ and salts thereof represented by the following general formula (I) antimycin represented by A ₅ and the following general formula (II) It provides an actinomycete-produced metabolite comprising at least one member selected from the group consisting of:

[0017]

Embedded image

[In the formula (I), R ₁ represents a sec-butyl group or an isobutyl group. In the formula (II), R ₂ is n
-Represents a propyl group or an isopropyl group. ]

[0019]

Embodiments of the present invention will be described below. (1) Mixture of antimycin A compounds of the present invention The mixture of antimycin A compounds of the present invention is a mixture of antimycin A compounds containing a plurality of antimycin A compounds obtained as metabolites of actinomycetes. is there.
Actinomycetes producing such a mixture of antimycin A compounds include Streptomyces sp. Newly isolated from soil in Ibaraki Prefecture by the present inventors. PO
L-129 strain (Streptomyces sp. POL-129). The bacteriological properties of the POL-129 strain are described below.

<1> Morphological characteristics The basic mycelia elongate, branch well, and do not break under normal conditions. Aerial hyphae grow abundantly on yeast / malt agar, starch agar, nutrient agar, etc., and form a linear, long spore chain. Sporulation is slow and is characterized by a very thin spore chain. Observation with an electron microscope shows that the spores are elliptical or short cylindrical and the surface is smooth. Spores are usually 20-50
Individual chains. No spores, motile spores, sclerotia, etc. are observed.

<2> Properties on Various Media The growth state of the POL-129 strain on various media is as shown in Table 1. The standard shown in parentheses for the description of colors is "Color Harmony Manua" (Color Harmony Manua) manufactured by Container Corporation of America.
l)). Observation is 14 ~ 2 at 28 ℃
Performed after one day of culture.

[0022]

[Table 1]

<3> Physiological properties Growth temperature range: 15 ~ on yeast / malt agar
It grows in a temperature range of 37 ° C and grows well at 25-30 ° C. 2. 2. Liquefaction of gelatin: negative 3. Hydrolysis of starch: positive 4. Nitrate reduction: positive 5. Peptone conversion of skim milk: negative 6. Coagulation of skim milk: negative Melanin-like pigment formation: Negative in tryptone yeast liquid and tyrosine agar, peptone yeast
Positive on iron agar. <4> Utilization of carbon source 1. Carbon sources used: D-glucose, D-fructose, D-xylose, D-mannitol, L-arabinose, rhamnose, raffinose, melibiose, inositol. Unused carbon sources: sucrose, cellulose

<5> Cell Wall Composition The method of Becker et al. (Appl. Microbiol. 13:23)
6, 1965), the diaminopiperic acid in the cell wall component was of the LL type.

From the above properties, the POL-129 strain belongs to the genus Streptomyces among actinomycetes, and has a white to pink aerial mycelium color, a linear aerial hyphae, a smooth spore surface, and a reverse color tone. Is brown and does not produce melanin-like pigment in tryptone yeast liquid and tyrosine agar, but is summarized as a strain produced in peptone yeast and iron agar.

The present inventors have determined that this strain of POL-129 is Streptomyces sp. POL-129 (Strept
omyces sp. POL-129). In addition, PO
The L-129 strain has been registered with the FERM P-156 from June 7, 1996 by the Institute of Biotechnology and Industrial Technology, National Institute of Advanced Industrial Science and Technology (zip code 305, 1-3 1-3 Higashi, Tsukuba, Ibaraki, Japan).
Deposited as 77.

The POL-129 strain is easily changed in its properties as seen in other actinomycetes.
129 strains or mutants derived from this strain, even transformant conjugates or genetic recombinants, as long as it has the ability to produce antimycin A ₅ and / or A _6, both the invention Can be used.

The mixture of the antimycin A compound of the present invention obtained as a metabolite of such an actinomycete contains a plurality of antimycin A compounds and contains an antimycin A5 represented by the following general formula (I). And at least one selected from the group consisting of antimycin A ₆ represented by the following general formula (II) and salts thereof, in a total amount of 50 mol% or more, preferably 60 mol%, based on the total amount of the mixture. It is characterized by including the above. That is, in the mixture, which antimycin A ₅ or a salt thereof and / or antimycin A ₆ or a salt thereof, is included in the selective, antimycin A ₅ or a salt thereof, or antimycin A ₆ or a in addition, although in each alone and antimycin a ₅ or a salt thereof with antimycin a ₆ or a salt thereof is less than the mol% the total amount of both the mole when the salt is each alone the mol% % In some cases.

[0029]

Embedded image

In the general formula (I), R ₁ represents a sec-butyl group or an isobutyl group. Specific examples of such compounds include the following compounds. Antimycin A ₅ a: 8- ethyl-3 - [[3- (formylamino) -2-hydroxy benzoyl] amino] -2,6-dimethyl-4,9-dioxo-1,5
Dioxonan-7-yl-2-methylbutanoate (when R ₁ is sec-butyl group) Antimycin A ₅ b: 8-ethyl-3-[[3- (formylamino) -2-hydroxybenzoyl] amino] -2,6-dimethyl-4,9-dioxo-1,5-
Dioxonan-7-yl-3-methylbutanoate (when R ₁ is an isobutyl group)

In the general formula (II), R ₂ represents an n-propyl group or an isopropyl group. Specific examples of such compounds include the following compounds. Antimycin A ₆ a: 8- ethyl-3 - [[3- (formylamino) -2-hydroxy benzoyl] amino] -2,6-dimethyl-4,9-dioxo-1,5
Dioxonan-7-yl-isobutanoate (R ₂
Is an isopropyl group) Antimycin A ₆ b: 8-ethyl-3-[[3- (formylamino) -2-hydroxybenzoyl] amino] -2,6-dimethyl-4,9-dioxo-1,5 −
Dioxonan-7-yl-n-butanoic acid ester (R ₂
Is an n-propyl group. The salts of these antimycin A-based compounds are not particularly limited as long as they are physiologically acceptable general ones. Examples thereof include alkali metal salts such as sodium salt and potassium salt of the antimycin A-based compound, and alkali metal earth salts such as calcium salt and magnesium salt.

[0032] Mixtures of antimycin A compound of the present invention preferably comprises a antimycin A _5, or a salt thereof with antimycin A _6, or a salt thereof, and a molar ratio, antimycin A _5, or a salt thereof : Antimycin A ₆
Or its salt = 90-50: 10-50, more preferably 90-60: 10-40. That is, the main component of the mixture is antimycin A _5, preferably antimycin A ₅ are the total mixture of 30% or more, more preferably accounts for 40% or more.

Preferably, the mixture of the antimycin A-based compound of the present invention comprises the antimycin A ₅ a, A ₅
b, A ₆ a, and A ₆ b, and salts thereof. Further, in antimycin A _5, or a salt thereof, A ₅ a or percentage of a salt thereof and A ₅ b or a salt thereof, A ₅ a or its salt: A ₅ b or its salt = 1: 2 to 1: 5 It is about. That is, the main component of the mixture is more specifically antimycin A ₅ b.

The mixture of the present invention has an action such as vasodilation by itself. Therefore, it can be used as a medicine, specifically as a hypotensive agent and the like.

(2) Method for Producing a Mixture of Antimycin A Compounds The mixture of antimycin A compounds of the present invention can be prepared using Streptomyces sp. After the POL-129 strain is cultured to produce a mixture of the antimycin A-based compounds, it can be produced by a method comprising a step of purifying the culture solution.

In the method of the present invention, the aforementioned POL-
The 129 bacteria are cultured in a medium containing nutrients that can be used by ordinary microorganisms. As the nutrient source, known nutrients conventionally used for cultivation of actinomycetes can be used. For example, glucose, dextrin, starch, molasses, animal and vegetable oils and the like can be used as the carbon source. As a nitrogen source, meat extract, soybean flour, wheat germ, corn steep liquor, peptone, yeast extract, ammonium sulfate, sodium nitrate, urea and the like can be used. In addition, if necessary, it is effective to add sodium, potassium, calcium, magnesium, cobalt, chlorine, phosphoric acid, sulfuric acid, and other inorganic salts capable of generating ions. Also, helping the growth of bacteria, antimycin A ₅ or a salt thereof and / or antimycin A ₆ or a salt thereof (hereinafter sometimes referred to as "antimycin A _5, etc.".) Organic that promotes the production of And inorganic substances can be appropriately added.

As the culture method, a culture method under aerobic conditions, particularly a shaking culture method, is most suitable. Suitable temperatures for cultivation are 15-37 ° C, but often 25-30 ° C.
Incubate at ° C. Production of antimycin A ₅ and A ₆ may vary by medium and culture conditions, the accumulation reaches the maximum usually between 1-4 days. Accumulation amount of such antimycin A ₅ stops culture when reaching a maximum, according to a general method may be performed isolation of the product for collecting fermentation products.

Specifically, the obtained culture solution is filtered, and the filtrate may be purified by a general purification step such as solvent extraction or column chromatography. Thus, it is possible to obtain a culture purified product containing antimycin A _5, and the like. In addition, a physiologically acceptable salt of the resulting antimycin A-based compound can be obtained by dissolving the purified culture product in a polar or nonpolar solvent and adding an appropriate amount of an acid or base.

The cultures purified product thus obtained are those comprising a compound selected from antimycin A ₅ and antimycin A ₆ and salts thereof, thereby the mixture of antimycin A compound of the present invention Obtained as a metabolite of actinomycetes.

The obtained culture purified product is further subjected to high-speed liquid chromatography.
Use chromatography, thin-layer chromatography, etc.
Antimycin A_Fivea, A
_Fiveb, A ₆a and A₆b can be isolated individually.
You.

As described above, in the production method of the present invention, there has been no conventional production method alone, and even if it is produced as a mixture, antimycin A is obtained only in a very small amount.
₅ and / or the antimycin A _6, in which made it possible to produce them as a main component mixture. Further, each antimycin A-based compound can be further isolated from the mixture, which can contribute to research on antimycin A-based compounds and the like.

(3) Pharmaceutical composition of the present invention The pharmaceutical composition of the present invention contains, as an active ingredient, a mixture of the aforementioned antimycin A compounds. That is, the mixture of the present invention has an action such as vasodilation, and can be contained in a pharmaceutical composition as a drug such as a hypotensive agent.

The pharmaceutical composition of the present invention suitably contains, in addition to the mixture of the antimycin A-based compound of the present invention, optional ingredients used in usual pharmaceutical compositions for formulation according to the purpose. be able to. Optional components include excipients, extenders, binders, coatings, sugar coatings, stabilizers, disintegrants, coloring agents, lubricants, pH adjusters, solubilizers, dispersants,
Examples include a thickener, an isotonic agent, and the like. The administration method is not particularly limited, and examples include oral administration and administration by injection. Further, the dosage form of the pharmaceutical composition of the present invention can be appropriately selected according to the administration method such as an injection.

[0044]

Embodiments of the present invention will be described below.

[0045]

Example 1 (1) Production of Antimycin A Compound of the Present Invention In this example, POL-129 strain was cultured, and the culture solution was purified to culture the antimycin A compound of the present invention. A purified product was obtained. The method is described below step by step.

First, as a seed medium, yeast extract 1.0 was used.
% And glucose 1.0%.
Further, as a production medium, a medium having a composition of 0.15% of meat extract, 0.5% of peptone and 0.25% of sodium chloride was prepared. In addition, each medium was adjusted with ion-exchanged water, and the pH before sterilization was adjusted to pH 7.0 before use.

10 ml of the seed medium was dispensed into an L-shaped test tube and sterilized at 121 ° C. for 15 minutes. Next, Streptomyces sp. The POL-129 strain was inoculated with 1 to 2 platinum loops of slant agar culture and shake-cultured at 28 ° C. for 60 hours, which was used as seed culture.

3.4 L previously sterilized at 121 ° C. for 15 minutes
100 μL of an antifoaming agent antifloss was added to three 5 L jar fur mentors containing the production medium described above, and then 34 ml of the above seed culture was inoculated, and incubated at 28 ° C. for 27 hours at 250 rpm.
The culture was performed with aeration and stirring at pm. After completion of the culture, diatomaceous earth was added as a filter aid, followed by filtration to obtain a filtrate. 1 obtained
The 0 L filtrate was subjected to solvent extraction three times using a total of 21 L benzene, and the organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 413 mg of a crude product. 413 mg of the obtained crude product was dissolved in benzene, and 100 g of silica gel (BW-820MH, manufactured by Fuji Silysia Chemical Ltd.) was used.
Column was adsorbed after equilibration with benzene, benzene 1.75 L, then benzene: ethyl acetate (10: 1)
1.935 L (fractionation into nine 215 ml portions), 1.8 L benzene: ethyl acetate (5: 1) (8 225 ml portions)
(Fractioned into a book). Benzene: ethyl acetate (1
0: 1) benzene: ethyl acetate (5: 1) 7
The active fractions up to the first run were combined and concentrated to obtain 32 mg of the above-mentioned culture purified product as a brown oily liquid.

FIG. 1 shows the ¹ H-NMR spectrum of the purified culture product measured at 270 MHz in CDCl ₃ . FIG.
The ¹³ C-NMR spectrum of the culture purified product measured at 67.5 MHz in CDCl ₃ is shown in FIG. FIG. 3 shows methanol-5 mM tetrabutylammonium phosphate (pH
= 3) UV of the culture purified product measured in (68:32)
The spectrum is shown. FIG. 4 shows a high performance liquid chromatograph of the culture purified product obtained under the following conditions. In addition, antimycin A (Sigma (S
FIG. 5 shows a high-performance liquid chromatograph manufactured by IGMA).

Mobile phase: methanol: 5 mM tetrabutylammonium phosphate (pH = 3) (= 68: 32) Flow rate: 1.2 ml / min Detection: 220 nm column: TSK-gel ODS-80TM (4.6 mm)
I. D. * 25cm)

[0051] From the above analysis, in the culture purification of POL-129 strain, with respect to the total mixture of antimycin A compound, antimycin A ₅ 42.3 mol%,
And A ₆ are included 22.0 mol%, the sum of antimycin A ₅ and A ₆ was found to contain 64.3 mole%.

(2) Evaluation of Relaxation Activity on KCl-Induced Contraction The obtained cultured product was examined for its relaxation activity on KCl-induced contraction using rat isolated aorta.

<Method> 4.78 mg of the purified culture was weighed, dissolved in 2 ml of benzene, and dissolved in 0.3 ml of benzene.
, And concentrated by centrifugation to dryness (0.717 m
g). This was dissolved in 0.5 ml of methanol (1.4).
340 mg / ml). (Hereinafter referred to as solution A) 0.25 ml of methanol was added to 0.25 ml of solution A (0.7170 mg / ml). (0.25 ml of the methanol solution) was added to 0.25 ml of the methanol solution (0.3585 mg / ml). 0.25 ml of methanol was added to 0.25 ml of the liquid C (0.1793 mg / ml). (This is referred to as two liquids.) 0.25 ml of methanol was added to 0.25 ml of the two liquids (0.0896 mg / ml). (It is referred to as solution E.) 0.25 ml of methanol was added to 0.25 ml of solution E (0.0448 mg / ml). (This is referred to as solution F.) To 0.25 ml of solution F, 0.25 ml of methanol was added (0.0224 mg / ml). (0.25 ml of methanol solution) was added to 0.25 ml of methanol solution (0.0112 mg / ml). (Hereinafter referred to as solution H) 0.25 ml of methanol was added to 0.25 ml of solution H (0.0056 mg / ml). (This is referred to as a liquid.) 0.25 ml of methanol was added to 0.25 ml of the liquid (0.0028 mg / ml). (This is referred to as a solution.) To 0.25 ml of the solution, 0.25 ml of methanol was added (0.0014 mg / ml). (To be referred to as a liquid) 0.25 ml of methanol was added to 0.25 ml of the liquid (0.0007 mg / ml). (The solution is referred to as “ヲ solution.”) 0.25 ml of methanol was added to 0.25 ml of the solution (0.0004 mg / ml). (It will be a liquid.)

50 μl of the solutions A to W were each subjected to the assay, and the measurement was performed twice per sample. All assays used WistarRat (male) thoracic aortic ring specimens to examine their relaxation activity against 25 mM KCl-induced contractions.

<Results> The results obtained are shown in FIG. The horizontal axis is the dose (ng), and the vertical axis is the relaxation activity (%). From this graph, the activity was determined as the concentration in the Magnus tube (the buffer in the Magnus tube was 10 ml), and the activity was 7 ng / ml to 11 mg / ml.
Almost concentration dependency was observed in the range of 2 ng / ml. The equation obtained by taking the five points in this range by the least squares method is:
Y = −97.08 + 59.130 Log (X),
The correlation coefficient was 0.885. From this equation, the concentration required for 50% relaxation is 32 ng / ml, and if the molecular weight is 500, the IC ₅₀ is 10 ⁻⁸ to 10 ⁻⁷ M.
This clearly shows that the purified product of this culture has a vasodilator effect, and is useful for treating cardiovascular diseases such as hypertension.

[0056]

Mixture of antimycin A compound of the present invention according to the present invention are those containing antimycin A ₅ and A ₆ as the main component, it can contribute to the study of physiological activity such as antimycin A ₅ and A ₆ Things. Further, according to the production method of the present invention, among a series of antimycin A-based compounds,
The antimycin A ₅ and A ₆ selectively and can be efficiently manufactured.

[Brief description of the drawings]

¹ H-NMR of [1] cultures purified product obtained in Example 1
It is a figure showing a spectrum.

FIG. 2 shows the ¹³ C-NM of the purified culture obtained in Example 1.
It is a figure showing an R spectrum.

FIG. 3 is a view showing a UV spectrum of a purified culture product obtained in Example 1.

FIG. 4 is a view showing a high-performance liquid chromatograph of the purified culture product obtained in Example 1.

FIG. 5 is a diagram showing a high-performance liquid chromatograph of a control product in Example 1.

FIG. 6 is a graph showing the relaxation activity of the culture purified product obtained in Example 1 on KCl-induced contraction using a rat isolated aorta.

[Explanation of symbols]

Peak of A ₁ ... antimycin A ₁ of the peak A ₂ ... antimycin A ₂ peaks A ₃ peaks of ... antimycin A ₃ A ₄ ... antimycin A ₄ A ₅ ... Anti peak peak a ₆ · · · antimycin a ₆ of hygromycin a ₅ B · · · formula Y = -97.08 + 59.130Log
(X) A straight line representing [correlation coefficient: 0.885].

 ──────────────────────────────────────────────────の Continuing on the front page (72) Inventor Chihiro Sato 560 Pola, Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Prefecture Inside the Tokazuka Research Laboratories Co., Ltd. Inside Totsuka Laboratory Co., Ltd. (72) Inventor Kenichi Goto 560 Pola Kasei Kogyo Co., Ltd.

Claims (6)

[Claims] 1. A mixture of antimycin A compound comprising a plurality of antimycin A compound obtained as a metabolite of actinomycetes, antimycin A ₅ and the following general represented by the following general formula (I) An antimycin comprising at least one selected from the group consisting of antimycin A ₆ represented by the formula (II) and salts thereof in a total amount of 50 mol% or more based on the total amount of the mixture. A mixture of A-based compounds. Embedded image [In the formula (I), R ₁ represents a sec-butyl group or an isobutyl group. In the formula (II), R ₂ represents an n-propyl group or an isopropyl group. ] 2. The method according to claim 1, wherein the mixture of the antimycin A-based compounds is Streptomyces sp. The mixture of an antimycin A-based compound according to claim 1, which is obtained as a metabolite produced by the POL-129 strain. 3. An antimycin A ₅ represented by the general formula (I) or a salt thereof and an antimycin A ₆ represented by the general formula (II) or a salt thereof, and the molar ratio thereof is: antimycin A _5, or a salt thereof: antimycin A ₆
Or a salt thereof = 90 to 50:10 to 50.
A mixture of the described antimycin A-based compounds. 4. Streptomyces sp. POL-
The antimycin A-based compound according to claim 1, comprising: culturing 129 strains to produce a mixture of the antimycin A-based compound to obtain a culture solution containing the mixture; and purifying the culture solution. For producing a mixture of 5. A pharmaceutical composition containing the mixture of the antimycin A compound according to claim 1 as an active ingredient. 6. Streptomyces sp. POL-
A metabolite produced by the 129 strain, selected from the group consisting of antimycin A ₆ and salts thereof represented by the following general formula (I) antimycin represented by A ₅ and the following general formula (II) Including at least one of
Metabolite produced by actinomycetes. Embedded image [In the formula (I), R ₁ represents a sec-butyl group or an isobutyl group. In the formula (II), R ₂ represents an n-propyl group or an isopropyl group. ]