DESCRIPTIONS OF ANTIBIOTICS 



per nil. Active on ('. albicans in the mouse intes- 

 tinal tract (2). Not active on streptomycetes (4). 



Toxicity: LDao (mice) 25 mg per kg intraperi- 

 toneally (2) ; also 40 to 50 mg per kg intraperitone- 

 ally, 2.5 to 4.0 mg per kg intravenously, and 750 

 to 1200 mg per kg orally (3). Toxic to conjunctiva 

 (3). 



Utilization: Used tojjically. orally, and par- 

 enterally. Active on vaginal trichomoniasis (3). 



References: 



1. Uri, J. Acta Physiol. Acad. Sci. Hung. 11: 



(suppl.) 103-104, 1957. 



2. Bekesi, I. Nature, London 1«1: UOS, 1958. 



3. Kelentey, B. et al. Ahstr. Conununs. Sym- 



posium on Antil)iotics, Prague, pj). 67-68, 

 1959. 



4. Uri, J. Arzneimittel-Forsch. 9: 175-181, 



1959. 



Fradicin 



Produced by: Streptoniyces fradiac (1). 



Synonym: Factor X (1). 



Method of extraction : I. Broth-filtrate extracted 

 with n-butanol at pH 7.0. Kxtract concentrated 

 to dryness in vacuo. Residue taken up in 95 per 

 cent ethanol, concentrated, and added dropwise 

 to acetone. Solution concentrated //; vacuo and 

 added dropwise to petrole\mi ether. Supernatant 

 discarded. Residual oil dissolved in t-butanol and 

 lyophilized (1). H- Culture filtered with the aid 

 of Super-Cel. Cake extracted with isopropanol- 

 ethyl acetate (1:10). Extract (A) concentrated to 

 give either a precipitate or a tarry residue. Etha- 

 nol solution of such residues chromatographed on 

 Super Filtrol Celite, developed with ethanol, then 

 with 10 per cent (volume per volimie) ammonia 

 in ethanol (3). Active fractions concentrated and 

 jirecipitated by scratching the side of the flask 

 containing the concentrate. Extract A can also be 

 treated by adjusting the i)H to 5.8 and stirring 

 with Stoddard solvent to separate two phases. 

 Lower phase adjusted to pH 8.0 to 8.5 to precipi- 

 tate fradicin. Crystallized from hot ethylene di- 

 chloride on cooling. Further purified by chroma- 

 tography on Florisil with 1,4-dioxane as solvent 

 and developer (3). 



Chemical and physical properties: Weak base. 

 Light green-yellow crj'stals. No definite melting 

 point. Darkens at about 180-300°C. Most soluble 

 in dioxane, propylene glycol, ethylene dichloride, 

 and other chlorinated hydrocarbon solvents. In- 

 soluble or very sparingly soluble in cyclohexane, 

 xylene, and petroleum ether. Slightly soluble in 

 water. Ultraviolet absorption spectrum maxima 

 at about 242 and 292 ni/x, with a shoulder at 265 

 mn (absolute methanol) (1). Lltraviolet spectrum 



of this pre{)aration shows the presence of a con- 

 taminating hexaene, probably the same as the 

 biologically inactive hexaene later reported to be 

 produced by this strain of S. fradiae (8). {a]^^ = 

 +65° (c = 1.0 per cent in 1,4-dioxane). More 

 stable at neutrality than at pH 2.0. Neutral ec^uiv- 

 alent, 498 to 514. C30H34N4O4 : C = 70.29%; H = 

 6.59%; N = 10.86%; O— CH. = 11.95%. Molecvdar 

 weight, about 500 (Barger). Hydrochloride: Nee- 

 dles. Darken on exposure to light. Alkali fusion 

 yields a volatile product which gives positive 

 pine-splint and l%hrlich (pyrrol) tests (1-3). 



Bioloyind (uiivitji: Active on yeasts and fungi. 

 Active on certain protozoa, such as Trypanosoma 

 cruzi and Endamoeba histolytica. Not active on 

 bacteria (1, 5, 7). Activity strong at pH >7.0; 

 greatly reduced at lower i)H (1, 2). Cysteine and 

 other reducing agents decrease antifungal activitj" 

 (4), as do oleate and Tween 80 (6). 



Toxicity: LDjo (mice) 4 mg per kg intraperi- 

 toneally and orally. Irritating to rabbit skin at 

 50 Mg per gm of a hydroi)hilic ointment (5). 



References: 



1. Swart, E. A. et al. Proc. Soc. Exptl. Biol. 



Med. 73: 376-378, 1950. 



2. Hickey,R. J. andHidy, P. H. Science 113: 



361-362, 1951. 



3. Hidy, P. H. and Hickey, R. J. Arch. Bio- 



chem. Biophys. 34: 67-71, 1951. 



4. Waksman, S. A. et al. Bull. World Health 



Organization 6: 163-173, 1952. 



5. Schwartz, J. A. et al. Trans. 11th Veterans 



Admin. Conf. Tuberc. 86-93, 1952. 



6. Hickey, R. J. Arch. Biochem. Biophys. 



46: 331-336, 1953. 



7. Packchanian, A. Am. J. Trop. Med. Hyg. 



2: 243, 1953. 



8. Steinman, I. 1). Thesis, Rvitgers University, 



1958. 



Fiatliciii-like An libiotic 



Produced by: Streptoniyces sp. differing from S. 

 fradiae and S. roseojlavus (mycelin-producer). 



Remarks: Authors (1) believe that the antibiotic 

 may also resemble mycelin. May be contaminated 

 with, or actually be a hexaene. 



Method of extraction: Mycelium extracted with 

 methanol. Extract washed with water and con- 

 centrated in vacuo. Ether added to the concentrate 

 to give a precipitate. 



Chemical and physical properties: Dark yellow 

 powder. Soluble in butanol, methanol, ethanol, 

 and pyridine. Slightly soluble in water. Insoluble 

 in chloroform, benzene, acetone, ethyl acetate, 

 ether, and petroleum ether. Ultraviolet absorption 

 spectrum maxima at 243, 294, 335, 355, and 373 mix. 



