DESCRIPTIONS OF ANTIBIOTICS 



309 



test agar prevents the action of the antil)iotic. 

 No activity against bacteria. 



Toxicity: Mice are not killetl by intraperitoneal 

 administration of 5 mg per kg; 25 mg per kg by 

 the same route kill mice. 



Reference: 1. Schmitz, H. and Woodside, R. 

 Antibiotics & Chemotherapy 5: 652-657, 1!)55. 



Myconiyceliii 



Produced bij: Strepfonii/ces arenae fgray-spored) 

 (1). 



Method of extraction: Antibiotic present mostly 

 in mycelimn. Extraction may be carried ovit l)y: 

 I. Organic solvents, inchiding methanol, acetone, 

 butanol, or t-butanol, at pH 4.0 to 10.0. Ex- 

 tract concentrated to a watery residue, and 

 residue e.xtracted with chloroform at pH 2.0 to 

 10.0. Chloroform chromatograi)hed on (a) silica 

 gel, and antibiotic eluted with chloroform con- 

 taining increasing amounts of methanol; or (bj 

 Darco C-OO, and eluted with methanol (80 i)er 

 cent ) -chloroform (20 per cent) containing 0.1 .V 

 HCl. II. Ivxtraction with 50 to 80 per cent etha- 

 nol. Extract evaporated to an acpieous residue and 

 extracted with butanol at pH 2 to 4. Re-extraction 

 into water at pH 10 (1). 



ChemicdJ and plujsical properties: Negatively 

 charged acitlic sul)stance. Countercurrent dis- 

 tribution studies (pH 7.0; water-butanol) indicate 

 presence of at least two substances, one more 

 soluble in water, the other in butanol. Soluble 

 in dilute NaOH, methanol, acetone, n-butanol, 

 and t-bvitanol. Alkali-metal salts soluble; precipi- 

 tate on acidification. Cu, Ca, Mg, and Pb salts 

 insoluble. Positive anthrone test. Negative Inuret 

 test. Molecular weight, about 10,000. Nondiffusi- 

 l)le; nondialyzable. Ultraviolet absorption spec- 

 tnun maximum at 260 ni/x (Eil'^ 70). Infrared 

 spectrum given in reference 1. Darkens at about 

 170°C; chars a little above 200°C. Contains C, H, 

 N, and <1 per cent S; no P. Precipitates with lead 

 acetate and may be regenerated on addition of 

 H2S or H2SO4 in acetone, methanol, or n-butanol 

 (1). 



Biological activity: Active mainly on mycobacte- 

 ria. Moderately active on gram-positive bacteria. 

 Active on streptomycin- and streptothricin- 

 resistant Staph, aureus. Not active on gram-nega- 

 tive bacteria or C. albicans (1). No in vivo activity 

 on tuberculosis in guinea pigs (2). 



References: 



1. Grundy, W. E. et at. Canadian Patent 

 515,162, August 2, 1955. 



2. CJrundy, W. E. Personal communication, 

 1958. 



Mycoiii_\ ciii 



Produced hi/: Xocardia acidophilus (10). 



Method of extraction: Cooled broth-filtrate ex- 

 tracted at pH 2.5 with hexane in a Podbielniak 

 extractor. Re-extracted into cold 0.5 per cent pH 

 7.5 sodium phosphate buffer. Buffer stirred with 

 cold methylene chloride, then adjusted to pH 2.0. 

 Extract dehydrated, decolorized, and crystallized 

 from the treated extract on cooling with dry ice- 

 acetone. Recrystallized from methylene chloride 

 or acetone (8). Can also be extracted from broth 

 with ether or amyl acetate (1). 



Chcuiii-iil and physical properties: Unsaturated 

 carl)oxylic acid. ( — )-3,5,7,8-n-tridecatetraene- 

 10, 12-diyiioic acid (9). Free acid: Colorless nee- 

 dles; m.p. 75°C (decomposes explosively). Soluble 

 in methylene chloride and acetone. Ultraviolet 

 absorption spectrum maxima at 267 ni/x (« = 

 67,000) and 281 m^ (e = 61,000) with an inflection 

 at 256 m/x (e = 35,000) (7, 8). Infrared absorption 

 spectnun given in reference 8. [a]f = —130° (c = 

 0.4 per cent in absolute ethanol). Highly unstable 

 to heat and oxidizing conditions. Half -life of crys- 

 tals at 27°C is 3 hours. Forms a precipitate with 

 alcoholic silver nitrate, which then darkens at 

 room temperature. Solution in li([ui(l ammonia 

 changes from yellow to green, to l>hie, to purple, 

 to red. Neutral eciuivalent, 198 (7, 8). Xa salt: 

 Relatively stable. Decomposes in acid (2). Methyl 

 ester: Crystalline; m.p. 44°C (decomposition). 

 Poorly sohibie in water. Biologically active. 

 CisHu.O., : C = 78.17%; H = 5.36%; C— CH, = 

 0.48%. Structure (7) given in Chapter 6. A rela- 

 tively stable, l)iologically active isomer of myco- 

 mycin, isomycomycin, has been prepared by treat- 

 ing a dilute aciueous solution of mycomycin with 

 dilute NaOH (1.0 A') at room temperature, then 

 treating the resulting precipitate with HCl at pH 

 2.0. Isomycomycin: 3,5-Tridecadiene-7,9,ll-tri- 

 3'noic acid (10). Long white needles. Decomposes 

 slowly when heated above 100°C. Soluble in ether, 

 ethanol, dioxane, ethyl acetate, and glacial acetic 

 acid. Slightly soluble in benzene, chloroform, and 

 carbon disulfide. Insoluble in hexane and petro- 

 leum ether. Ultraviolet absorption spectrum 

 maxima at 260 and 270 niyu with weak maxima at 

 290, 307, 327, and 348 ni/u. Infrared data given in 

 reference 10. C13H10O2 . Possible structural for- 

 mula given in Chapter 6. 



Biological activity: Active on gram-positive and 

 gram-negative bacteria, mycobacteria, and fungi 



