GB2293379A - WF17819 substance - Google Patents

Abstract

A compound designated WF17819 substance or a salt thereof having the physico-chemical properties described. A process for the production of WF17819 substance is disclosed and which comprises culturing a WF17819 substance-producing strain belonging to the genus Ochroconis in a nutrient medium and recovering the same. A pharmaceutical composition containing WF17819 substance or a salt thereof is also provided. The compound has antimicrobial activity against microorganisms such as Candida, Aspergillus and Cryptococcus, and is therefore useful for the therapeutic and prophylactic treatment of certain infectious diseases. WF17819 has the empirical formula C32H50O11.

Description

WF17819 SUBSTANCE The present invention relates to a novel antimicrobial compound, hereinafter referred to briefly as WF17819 substance.

More particularly, it relates to a novel compound, WF17819 substance or pharmaceutically acceptable salts thereof which have antimicrobial activity against microorganisms such as Candida, Aspey,oillus, Cryptococcus. etc. infectious diseases, to a process for preparation thereof, to a pharmaceutical composition containing the same, to a use of the same as a medicament, and to a method for treating such infectious diseases.

Accordingly, one object of this invention is to provide WF17819 substance or pharmaceutically acceptable salts thereof which have antimicrobial activity.

Another object of this invention is to provide a process for production of the WF17819 substance or salts thereof by fermentation of a WF17819 substance-producing strain such as Ochroconis sp. No. 17819 in a nutrient medium.

A further object of this invention is to provide a pharmaceutical composition containing, as an active ingredient, the WF17819 substance or salts thereof.

Still further object of this invention is to provide a use of the WF17819 substance or salts thereof as a medicament and a method for treating infectious diseases in human beings or animals.

The WF17819 substance can be produced by fermentation of the WF17819 substance-producing strain such as Ochroconis sp. No. 17819 in a nutrient medium.

It is to be understood that the production of the WF17819 substance is not limited to the use of the particular organism described herein, which is given for the illustrative purpose only. This invention also includes the use of any mutants which are capable of producing the WF17819 substance including natural mutants as well as artificial mutants which can be produced from the described organism by conventional means such as irradiation of X-ray, ultra-violet radiation, treatment with N-methyl-N'nitro-N-nitrosoguanidine, 2-aminopurine, and the like.

Particulars of Ochroconis sp. No. 17819 is as follows: Characteristics of producing strain No. 17819 The fungal strain No. 17819 was originally isolated from a litter collected in Ogawa-machi, Hiki-gun, Saitama-ken, Japan. This organism grew very restrictedly on various culture media, and formed yellowish white to brown colonies. The strain No. 17819 formed neither anamorph nor teleomorph on various media, while it produced only anamorph on a sporulation medium, contained the following components in grams per liter of deionized water: glycerol, 1; NaNO3, 0.5; KH2PO4, 0.2; yeast extract, 0.05; agar, 15. The conidiogenesis was holoblastic and conidiophore growth was sympodial. Its mycological characteristics were as follows.

Cultural characteristics on various agar media are summarized in Table 1. Culture on malt extract agar grew very restrictedly, attaining 1.0-1.5 cm in diameter after four weeks at 25"C. This colony surface was raised, smooth and yellowish white. The reverse was grayish yellow and pale yellow at the edge. Conidial structures were not observed.

Colonies on potato dextrose agar grew very restrictedly, attaining 1.0-1.5 cm in diameter under the same condition. The surface was raised, sulcate, wrinkly, felty, and grayish orange. The reverse was brownish orange. Conidial structures were not observed.

The morphological characteristics were determined on basis of the cultures on the sporulation medium. Conidiophores were macronematous, mononematous, unbranched, straight, septate, smooth, brown, 40-60(-80) Rm long, 4-6(-7) Fm wide, and formed some conidia around each apex or on the upper part. Conidiogenous cells were integrated, polyblastic, sympodial, cylindrical, elongated, cicatrized or denticulate. Conidia were solitary, oval to cylindrical, rounded at the apex and truncated at the base, 0-1(-2) septate, sometimes constricted at the septum, pale brown, smooth, 7-12 x 4-6 Fm in size. The vegetative hyphae were smooth, septate, hyaline and branched. The hyphal cells were cylindrical and 2-5 Fm in diameter.

Strain No. 17819 was able to grow at the temperature range from 7 to 28"C with the growth optimum at 19 to 27"C. These temperature data were determined on potato dextrose agar (made by NISSUI).

On the basis of taxonomic criteria by J. A. von Arx (The Genera of Fungi, Sporulating in Pure Culture, 2nd ed., 315 p., J. Cramer, Vaduz, 1974), above morphological characteristics indicate that strain No. 17819 resembles the hyphomycete genera Ochroconis de Hoog & von Arx 1973 or Veronaea Ciferri & Montemartini 1957. Ochroconis is characterized by the short, simple and denticulate conidiophores, producing ellipsoidal, pale brown conidia with a basal apiculation. And Veronaea is distinguished by the slender, brown and cicatrized conidiophores with small scars, and solitary and pale brown conidia. However, strain No.

17819 formed comparatively short, cicatrized or denticulate conidiophores and conidia without a distinct projection, on the sporulation medium. These characteristics are similar but not identical to those of Ochroconis or Veronaea. Strain No. 17819 is also similar in shapes of conidiophores to Dactylaria Saccard 1880, but its conidia are narrow, fusiform or vermiform. Thus, because of an uncertainty in the classification of this strain, it has been presumptively referred as Ochroconis sp. No. 17819.

Strain No. 17819 has been deposited to National Institute of Bioscience and Human-Technology, Agency of Industrial Science and Technology, Japan, as FERM P- 4474 (deposited date: August 18, 1994).

Table 1. Cultural characteristics of the strain No. 17819.

Medium Cultural characteristics Malt extract agar* G: Very restrictedly, 1.0-1.5 cm S: Circular, raised, smooth, observed no anamorph, yellowish white (4A2) R: Grayish yellow (4B4), pale yellow (4A3) at the edge Potato dextrose agar G: Very restrictedly, 1.0-1.5 cm (Difco 0013) S: Irregular, raised, sulcate, wrinkly, felty, observed no anamorph, grayish orange (6B3) R: Brownish orange (6C4) Czapek's solution agar* G: Very restrictedly, less than 0.5 cm S: Circular, plane, thin, observed no anamorph, yellowish white (3A2) R: Yellowish white (3A2) Sabouraud dextrose agar G: Very restrictedly, 0.5-1.0 cm (difco 0190) S: Circular to irregular, raised, sulcate, felty, observed no anamorph, brown (7E6), orange white (5A2) at the edge R: Brownish orange (5C4) Medium Cultural characteristics Oatmeal agar G: Very restrictedly, 1.0-1.5 cm (Difco 1552) S: Circular, raised, smooth, observed no anamorph, orange white (5A2) R: Reddish gray (7B2) Emerson Yp Ss agar G: Very restrictedly, 0.5-1.0 cm (Difco 0739) S: Circular to irregular, plane, thin, observed no anamorph, yellowish white (4A2) R: Pale yellow (4A3) Corn meal agar G: Very restrictedly, 1.0-1.5 cm (Difco 0386) S: Circular, plane, thin, observed no anamorph, pale yellow (4A3), white (lAl) at the edge R: Pale yellow (4A3) MY20 agar* G: Very restrictedly, 0.5-1.0 cm S: Circular to irregular, raised, sulcate, felty, observed no anamorph, orange white (6A2) R: Pale orange (6A3) Abbreviation: G: growth, measuring colony size in diameter S: colony surface, R: reverse.

* . The compositions of malt extract agar, Czapek's solution agar and MY20 agar were based on JCM Catalogue of Strains (Nakase, T., 5th ed., 503p., Japan Collection of Microorganisms and Life Science Research Information Section of the Institute of Physical and Chemical Research, Saitama, 1992).

These characteristics were observed after 28 days of incubation at 25"C. The color descriptions were based on the Methuen Handbook of Colour (A. Kornerup, and J. H. Wanscher, 3rd ed., 525 p., Methuen, London, 1978).

Production of the WF17819 substance The WF17819 substance is produced when the WF17819 substanceproducing strain is grown in a nutrient medium containing sources of assimilable carbon and nitrogen under aerobic conditions (e. g. shaking culture, aerobic submerged culture, etc.).

The preferred sources of carbon in the nutrient medium are carbohydrates such as glucose, sucrose, starch, fructose or glycerin, or the like.

The preferred sources of nitrogen are yeast extract, peptone, gluten meal, cotton seed flour, soybean meal, corn steep liquor, dried yeast, wheat germ, etc., as well as inorganic and organic nitrogen compounds such as ammonium salts (e. g. ammonium nitrate, ammonium sulfate, ammonium phosphate, etc.), urea or amino acid, or the like.

The carbon and nitrogen sources, though advantageously employed in combination, need not to be used in their pure form because less pure materials, which contain traces of growth factors and considerable quantities of mineral nutrients, are also suitable for use.

When desired, there may be added to the medium mineral salts such as sodium or calcium carbonate, sodium or potassium phosphate, sodium or potassium chloride, sodium or potassium iodide, magnesium salts, copper salts, zinc salts, cobalt salts, or the like.

If necessary, especially when the culture medium foams seriously a defoaming agent, such as liquid paraffin, fatty oil, plant oil, mineral oil or silicone, or the like may be added.

Agitation and aeration of the culture mixture may be accomplished in a variety of ways, such as agitation by a propeller or similar mechanical agitation equipment, by revolving or shaking the fermenter, and the like.

The fermentation is usually conducted at a temperature between about 10 C and 40"C, preferably 20"C to 30"C, for a period of about 50 hours to 150 hours, which may be varied according to fermentation conditions and scales.

When the fermentation is completed, the culture broth is then subjected for recovery of the WF17819 substance to various procedures conventionally used for recovery and purification of biological active substance. for instance, solvent extraction with an appropriate solvent or a mixture of some solvents, chromatography or recrystallization from an appropriate solvent or a mixture thereof.

WF17819 substance may be converted to its salt since it is acidic substance. The salt of the WF17819 substance can be prepared by a conventional manner, during or after the recovery and purification of the WF17819 substance.

Suitable salts of the WF17819 substance are conventional pharmaceutically acceptable salts and include a metal salt such as an alkali metal salt (e. g. sodium salt, potassium salt, etc.) and an alkaline earth metal salt (e. g. calcium salt, magnesium salt, etc.), an ammonium salt, an organic base salt (e. g. trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt, etc.), and the like.

WF17819 substance has the following physico-chemical properties: Appearance: white powder Molecular formula C32Q0O11 Molecular weight: 633 (FAB-MS m/z) (M + Na) HRFAB-MS: m/z Calcd for C32H50O11Na: 633.3251 (M + Na)+ Found: 633.3285 (M + Na)+ Ultraviolet absorption spectrum: Xmax (methanol) (1%, 1 cm): 264 (462), 234 (384) nm Solubility: Soluble: methanol, ethanol, acetone Slightly soluble: water Insoluble: n-hexane Color reaction: Positive: ceric sulfate reaction and iodine vapor reaction Negative: ninhydrin reaction, ferric chloride reaction, Molisch reaction and Ehrlich reaction Thin layer chromatography (TLC): Stationary phase Developing solvent Rf value Silica Gel 60F254s a mixture of dichloromethane (Extra Pure)* and methanol (1:1) containing 0.42 acetic acid (1%) HPTLC RP-18wF254s 55% aqueous acetonitrile 0.22 solution containing NH4H2PO4 (0.5%) High Performance Liquid Chromatography (HPLC): Condition: Mobile phase: 55% aqueous acetonitrile solution containing NH4H2PO4 (0.5%) Column: YMC-AM-303** (S-5, 120A ODS, 4.6mmID x 250mm) Flow rate: 1.0 ml/minute Detection: UV 260 nm Retention time: 9.1 minutes ** trade name:YMC Co., Ltd. (Kyoto, Japan) Infrared absorption spectrum: vmax (KBr): 3400, 2960, 2930, 2870, 1700, 1640, 1610, 1460, 1420, 1370, 1310, 1260, 1150, 1030 and 990cm~ 1H Nuclear magnetic resonance spectrum: (400 MHz, CD3OD) 8H 7.28 (1H, dd, J=16 and 10Hz), 6.26 (1H, dd, J=16 and 10Hz), 6.20 6.12 (2H, m), 6.00 (1H, dd, J=16 and 10Hz), 5.88 (1H, d, J=16Hz), 5.59 - 5.51 (2H, m), 5.34 (1H, m), 5.24 (1H, dd, J=16 and 8Hz), 5.02 (1H, dd, J=10 and 9Hz), 4.89 (1H, d, J=3.5Hz), 4.11 (1H, d, J=lOHz), 3.94 (1H, m), 3.89 - 3.81 (3H, m), 3.61 - 3.52 (3H, m), 3.42 (1H, m), 2.40 (1H, m), 2.15 (1H, m), 2.00 - 1.90 (3H, m), 1.37 - 1.20 (6H, m), 1.02 (3H, d, J=6.5Hz), 0.99 (3H, d, J=6.5Hz), 0.95 (3H, d, J=6.5Hz), 0.85 (3H, t, J=7Hz) as shown in Fig. 1 3C Nuclear magnetic resonance spectrum: (100 MHz, CD3OD) 6e 175.0. (s), 167.9 (s), 147.6 (d), 146.8 (d), 141.8 (d), 137.5 (d), 133.2 (d) 132.8 (d), 129.9 (d), 129.7 (d), 129.3 (d), 120.7 (d), 100.7 (d), 77.0 (d), 74.1 (d), 73.5 (d), 73.0 (d), 72.3 (d), 71.8 (d), 71.3 (t), 64.1 (t), 44.8 (d), 39.8 (d), 37.8 (d), 37.5 (t), 33.6 (t), 30.9 (t), 28.4 (t), 21.0 (q), 20.9 (q), 16.3 (q), 12.1 (q) as shown in Fig. 2 Nature: Acidic substance.

Now, in order to show the utility of the WF17819 substance, the test data on antimicrobial activity are shown in the following.

Antimicrobial activity of WF17819 substance Antimicrobial activity of WF17819 substance was determined by a serial broth dilution method in MEM, YNBD and Sabouraud media for Candida, Craptococcus and Aspergillus. The inoculum size was adjusted to 1 x 105 cfu/ml. Minimum effective concentration (MEC) is expressed in terms of pLg/ml after 24-48 hours incubation at 37"C in 5% CO2 incubator.

WF17819 substance had antimicrobial activity against Candida, Asperaillus and Crvptococcus. (Table 2) Table 2 MEM YNBD Sabouraud Candida albicans No. 7 0.39 1.56 1.56 Candida albicans No. 6406 1.56 12.5 6.25 Candida albicans FP578 0.39 0.78 0.39 Candida albicans FP629 0.78 3.13 1.56 Candida albicans FP633 12.5 25.0 > 50.0 Candida albicans FP1830 3.13 6.25 12.5 Aspereillus fumiaatus No. 1305 1.56 0.39 1.56 Aspeygillus fumioatus No. 8004 1.56 0.39 1.56 Asperaillus fumigatus No. FD050 3.13 0.78 3.13 Aspervillus fumiaatus No.S-43 3.13 0.20 3.13 Crvptococcus neoformans YC203 - 3.1 MEM: 9.4 g of Eagle's MEM and 2 g of NaHCO3 per liter of water YNBD: 6.7 g of Yeast Nitrogen Base (dehydrated; Difco) and 5 g of glucose liter of water Acute toxicity of WF17819 substance Acute toxicity of WF17819 substance in ICR mice (female; 4 week old) by subcutaneous injection was above 320 mg/kg.

For therapeutic administration, WF17819 substance or salts thereof are used in the form of conventional pharmaceutical preparation which contains said substance, as an active ingredient, in admixture with pharmaceutically acceptable carriers such as an organic or inorganic solid or liquid excipient which is suitable for oral, parenteral and external(topical) administration.

The pharmaceutical preparations may be in solid form such as tablet, granule, powder, capsule, suppository, solution, suspension, syrup, emulsion, lemonade, lotion, ointment, gel, and the like.

If needed, there may be included in the above preparations auxiliary substances stabilizing agents, wetting agents and other commonly used additives such as lactose, stearic acid, magnesium stearate, terra alba, sucrose, corn starch, talc, gelatin, agar, pectin, peanut oil, olive oil, cacao butter, ethylene glycol, tartaric acid, citric acid, fumaric acid, and the like.

While the dosage of the WF17819 substance may vary from and also depend upon the age, conditions of the patient, a kind of diseases, etc. In general. amount between about 0.1 mg and about 1,000 mg or even more, preferably between about 1 mg and about 500 mg per day may be administered to a patient. An average single dose of about 0.1 mg, 1 mg, 10 mg. 20 mg, 30 mg, 50 mg, 100 mg, 200 mg, 250 mg of the WF17819 substance may be used in treating infectious diseases.

The following Example is given for the purpose of illustrating this invention in more detail.

Example 1 (1) Fermentation First seed fermentation process was carried out as follows. A aqueous seed medium (10 ml) containing corn starch (1%), sucrose (3%), cotton seed flour (1%), dried yeast (1%), peptone (0.5%) and CaCO3 (0.2%) was poured into each of tubes and sterilized at 121"C for 30 minutes. A loopful of slant culture of Ochroconis sp. No. 17819 was inoculated into each of the medium and cultured at 250C for 12 days on a shaker.

Second seed fermentation process was carried out in a seed culture medium (80 ml) containing glycerine (1%), corn starch (2%), cotton seed flour (1%), gluten meal (1%) and potassium hydrogen phthalate (1%) (pH was adjusted to 5.2 with 6N NaOH) in a 225-ml flask.

Large scale fermentation process was carried out in a 30-liter jar fermenter. A production medium (20 liters) containing glycerine (1to), corn starch (2%), cotton seed flour (1%), gluten meal (1No) and potassium hydrogen phthalate (1%) (pH was adjusted to 5.2 with 6N NaOH), Adekanol LG-109 (defoaming agent, Asahi Denka Co., 0.05%) and Silicone KM-70 (defoaming agent, Shin-Etsu Chemical Co., 0.05%) was poured into the jar and sterilized at 121"C for 30 minutes. The seed culture obtained above was inoculated into the medium (2%) and cultured at 25"C for 10 days under aeration of 20 liters/minute (internal pressure . 1 kg/cm2) and agitation of 200 rpm.

(2) Isolation and Purification The culture broth (35 liters) was filtered. The filtrate was discarded.

Methanol (30 liters) was added to the mycelium cake with stirring. The mixture was allowed to stand for about 2 hours with intermittent stirring.

at room temperature. The resultant mixture was filtered and filtered cake was discarded. To the filtrate (34 liters) was added water (20 liters).

The resultant solution was passed through a column on Diaion HP-20 (1.5 liters; Mitsubishi Chemical Ind. Co.). The column was washed with 40% aqueous methanol (5 liters) and eluted with methanol (5 liters). Obtained eluate was concentrated in vacuo and the concentrate was subjected to column chromatography packed Silica Gel 60 (500 ml; made by E.

Merck; 70 - 230 mesh) packed with ethyl acetate. The column was eluted with ethyl acetate (1.5 liter), a mixture of ethyl acetate and acetone (1:1, 1.5 liters), acetone (1.5 liters), a mixture of acetone and methanol (3:1, 1.5 liters), a mixture of acetone and methanol (1:1, 1.5 liters) and methanol (1.5 liters), successively. The active fractions which were picked up from the fractions eluted with a mixture of acetone and methanol (3:1) and the fractions eluted with a mixture of acetone and methanol (1:1) were combined (2.25 liters). The combined active fractions was concentrated under reduced pressure. The obtained residue was dissolved with a mixture of chloroform and methanol (2: 1, 10 ml) and the solution was subjected to column chromatography of Silica Gel (300 ml; made by E. Merck; 230-400 mesh) packed with a mixture of chloroform and methanol (2:1).The column was eluted with a mixture of chloroform and methanol (2: 1; 1,400 ml) and a mixture of chloroform and methanol (1:1; 1,200 ml). The active fraction was concentrated under reduced pressure. The residue was dissolved with methanol (20 ml) and filtered. The obtained filtrate was subjected to column chromatography on reversed phase silica gel (300 ml; ODS-AM 120-S50, YMC Co.) packed with 70% aqueous methanol solution, and eluted with 70% aqueous methanol solution (900 ml), 75% aqueous methanol solution (900 ml), 80% aqueous methanol solution (900 ml), 85% aqueous methanol solution (900 ml), 90% aqueous methanol solution (900 ml), and methanol (900 ml), successively. The active fractions were diluted with the same volume of water and were passed through a column on Diaion HP-20 (200 ml; made by Mitsubishi Chemical Ind. Co.). The column was washed with 40% aqueous methanol solution (600 ml) and eluted with 95% aqueous methanol solution (600 ml). Obtained eluate was concentrated with reduced pressure and the residue was dissolved with a small volume of methanol and then a 20 fold of acetonitrile was added therein to give a white powder of WF17819 substance (1,190 mg)

Claims (7)

1. What we claim is: 1. WF17819 substance or a salt thereof, in which WF17819 substance has the following physico-chemical properties: Appearance: white powder Molecular formula C32,oO11 Molecular weight:

   633 (FAB-MS m/z) (M + Na) HRFAB-MS: m/z Calcd for C32H0O11Na: 633.3251 (M + Na)+ Found: 633.3285 (M + Na)+ Ultraviolet absorption spectrum: kmax (methanol) E (1%, 1 cm): 264 (462), 234 (384) nm Solubility: Soluble: methanol, ethanol, acetone Slightly soluble: water Insoluble: n-hexane Color reaction: Positive: ceric sulfate reaction and iodine vapor reaction Negative: ninhydrin reaction, ferric chloride reaction, Molisch reaction and Ehrlich reaction Thin layer chromatography (TLC): Stationarv phase Developing solvent Rf value Silica Gel 60F254s a mixture of dichloromethane (Extra Pure)* and methanol (1:1) containing 0.42 acetic acid (1%) HPTLC RP-l8WF254s 55% aqueous acetonitrile 0.22 solution containing NH4H2PO4 (0.5%) * made by E.Merck High Performance Liquid Chromatography (HPLC): Condition: Mobile phase: 55% aqueous acetonitrile solution containing MH4H2PO4 (0.5%) Column: YMC-AM-303** (S-5, 120 ODS, 4.6mmID x 250mm) Flow rate: 1.0 ml/minute Detection: UV 260 nm Retention time: 9.1 minutes ** trade name: YMC Co., Ltd. (Kyoto, Japan) Infrared absorption spectrum: vmax (KBr): 3400, 2960, 2930, 2870, 1700, 1640, 1610, 1460, 1420, 1370, 1310, 1260, 1150, 1030 and 990 cm-1 1H Nuclear magnetic resonance spectrum: (400 MHz.CD3OD) bH 7.28 (1H, dd, J=16 and 10Hz), 6.26 (1H, dd, J=16 and 10Hz), 6.20 6.12 (2H. m), 6.00 (1H, dd, J=16 and 10Hz), 5.88 (1H, d. J=l6Hz), 5.59 - 5.51 (2H, m), 5.34 (1H, m), 5.24 (1H, dd, J=16 and 8Hz), 5.02 (1H. dd, J=10 and 9Hz), 4.89 (1H, d, J=3.5Hz), 4.11 (1H, d, J=lOHz), 3.94 (1H, m), 3.89 - 3.81 (3H, m), 3.61 - 3.52 (3H, m), 3.42 (1H. m), 2.40 (1H, m), 2.15 (1H, m), 2.00 - 1.90 (3H, m), 1.37 - 1.20 (6H, m), 1.02 (3H, d, J=6.5Hz), 0.99 (3H, d, J=6.5Hz), 0.95 (3H, d, J=6.5Hz), 0.85 (3H, t, J=7Hz) as shown in Fig. 1 13C Nuclear magnetic resonance spectrum:: (100 MHz, CD3OD) 5C 175.0. (s), 167.9 (s), 147.6 (d), 146.8 (d), 141.8 (d), 137.5 (d), 133.2 (d), 132.8 (d), 129.9 (d), 129.7 (d), 129.3 (d), 120.7 (d), 100.7 (d), 77.0 (d), 74.1 (d), 73.5 (d), 73.0 (d), 72.3 (d), 71.8 (d), 71.3 (t), 64.1 (t), 44.8 (d), 39.8 (d), 37.8 (d), 37.5 (t), 33.6 (t), 30.9 (t), 28.4 (t), 21.0 (q), 20.9 (q), 16.3 (q), 12.1 (q) as shown in Fig. 2 Nature: Acidic substance.
2. 2. A process for production of WF17819 substance or a salt thereof, which comprises culturing a WF17819 substance-producing strain belonging to the genus Ochroconis in a nutrient medium and recovering the same.
3. 3. A process of Claim 2, in which a WF17819 substance-producing strain belonging to the genus Ochroconis is Ochroconis sp. No. 17819.
4. 4. Biological pure culture of Ochroconis sp. No. 17819.
5. 5. A pharmaceutical composition containing WF17819 substance or a salt thereof.
6. 6. A use of WF17819 substance or a salt thereof as a medicament.
7. 7. A method for treating or preventing infectious diseases which comprises administrating WF17819 substance or a salt thereof to human beings or animals.