Lucknomycin and process for producing same

• US 4,056,615 A
• Filed: 05/24/1976
• Issued: 11/01/1977
• Est. Priority Date: 05/28/1975
• Status: Expired due to Term

• Current Assignee: UCB Societe Anonyme
• Original Assignee: UCB Societe Anonyme
• Inventors: Vora, Vinay Chhotalal, Mody, Amrut Vithaldas
• Primary Examiner(s): Meyers, Albert T.
• Assistant Examiner(s): Stephens, Daren M.
• Application Number:
  US05/689,145
• Time in Patent Office: 526 Days
• Field of Search: 424/120
• US Class Current: 424/120
• CPC Class Codes: C12P 1/06 by using actinomycetales

Abstract

Antifungal and antiprotozoal antibiotic lucknomycin is producible by culturing Streptomyces diastatochromogenes var. Krains in an aqueous nutrient medium under submerged aerobic conditions. Lucknomycin is active against Candida albicans, Candida tropicalis, Candida krusei, Aspergillus niger and more particularly against Trichomonas vaginalis.

Claims

1. Lucknomycin, an antifungal and antiprotozoal antibiotic, which:

a. is an orange yellow powder;

b. starts to decompose at about 150°

C. but, even at 300°

C., does not melt;

c. has a molecular weight of about 1240;

d. has the following elemental analysis;

C, 58.92, H, 7.58;

N, 2.29;

e. is soluble in pyridine, dimethylformamide and dimethylacetamide, less soluble in 60% methanol, concentrated ethanol and isopropanol and is insoluble in benzene, acetone, water, chloroform, absolute ethanol, cyclohexane, ethyl acetate and diethyl ether;

f. gives an intense blue coloration in sulfuric acid;

g. has the following infrared absorption spectrum in a KBr pellet (in cm^-1);

space="preserve" listing-type="tabular">______________________________________ 3400 (S) 1465 (W) 1075 (S) 3100 (W) 1390 (W) 1045 (W) 2930 (S) 1350 (W) 1010 (S) 2860 (M) 1325 (W) 995 (W) 1715 (M) 1295 (W) 940 (W) 1650 (M) 1250 (W) 890 (W) 1600 (S) 1185 (S) 850 (M) 1575 (W) 1140 (W) 835 (W) 1545 (W) 1110 (M) 800 (W) ______________________________________

wherein S means strong absorption, M medium absorption and W weak absorption;

h. has the following ultraviolet absorption spectrum taken at a concentration of 1 mg. per 100 ml. of dimethylformamide;

space="preserve" listing-type="equation">344 mμ

(ε

= 3.5 ×

10.sup.4)

space="preserve" listing-type="equation">364 mμ

(ε

= 5.52 ×

10.sup.4)

space="preserve" listing-type="equation">384 mμ

(ε

= 8.04 ×

10.sup.4)

space="preserve" listing-type="equation">408 mμ

(ε

= 6.6 ×

10.sup.4)

i. has an optical rotation [α

]_D²⁵°

C. = 187°

to 194°

(C = 0.3% in dimethylformamide at 25°

C); and

j. is an aromatic heptaene giving by retroaldolization reaction p-N-methylamino-acetophenone and which contains mycosamine as a substituent and which has no titratable carboxyl group.

2. An antifungal and antiprotozoal composition which comprises an effective amount of lucknomycin according to claim 1 in admixture with a pharmaceutically acceptable carrier.

3. The antifungal and antiprotozoal antibiotic lucknomycin, according to claim 1, in its essentially pure form.

4. A process for making the antifungal and antiprotozoal antibiotic defined in claim 1, which comprises cultivating Streptomyces diastatochromogenes var. Krains CBS 101.74, in an aqueous nutrient medium under submerged aerobic conditions until substantial antifungal and antiprotozoal antibiotic activity is imparted to said medium by the production of lucknomycin.

5. A process according to claim 4, which comprises cultivating Streptomyces diastatochromogenes var. Krains CBS 101.74, in an aqueous nutrient medium containing a source of assimilable carbon and a source of assimilable nitrogen under submerged aerobic conditions until substantial antifungal and antiprotozoal antibiotic activity is imparted to said medium by the production of lucknomycin and isolating the lucknomycin so produced.

6. A process according to claim 5, in which the isolation comprises filtering the medium to obtain a solid residue and a filtrate, extracting the solid residue with a lower alkanol, concentrating the extract, treating the residue successively with hexane, chloroform and diethyl ether to eliminate an antibacterial polypeptide substance and recovering lucknomycin from said residue.

7. A process according to claim 6, in which lucknomycin is recovered from the filtrate by extraction with normal butanol.