348 



DESCRIPTIONS OF ANTIBIOTICS 



18. Bortle, L. andOleson,.). J. Antibiotics Ann. 



770-776, 1954-1955. 



19. Hewitt, R. I. et al. Antilnotics & Chemo- 



therapy 5: 139-144, 1955. 



20. Trincao, C. et al . Antil)iotics & Chemo- 



therapy 5: 505-507, 1955. 



21. Farber, S. Am. J. Pathol. U: 582, 1955. 



22. Wright, J. C. et al . Arch. Internal Med. 



96:61-77, 1955. 



23. MacKneson, R. (!. and Onnsby, H. L. Am. 



J. Ophthalmol. 39: 689-691, 1955. 



24. Oleson, J. J. et al. Acta Unio. Intern, con- 



tra Cancrum 11: 161-166, 1955. 



25. Halliday, S. L. et ul. Cancer Research 15: 



693-696, 1955. 



26. Baker, B. R. et al. J. Am. Chem. Soc. 77: 



1-7, 1955. 



27. Gumble, A. R. et al. Antiljiotics Ann. 



260-265, 1955-1956. 



28. Wilmot, A. J. Antibiotics Ann. 319-323, 



1955-1956. 



29. Trincao, C. et al. Antibiotics Ann. 596- 



599, 1955-1956. 



30. Taylor, A. E. R. et al. Brit. J. Pharmacol. 



11: 71-73, 1956. 



31. Tomisek, A. et al. Plant Physiol. 32: 7-10, 



1957. 



32. Sugiura, K. et al. Cancer Research 18: 



66-77, 1958. 



33. Fryth, P. W. et al. J. Am. Chem. Soc. 80: 



2736-2740, 1958. 



PyridoiTiycin 



Produeed by: Streptomyces pyridauit/cetinis (6,7), 

 formerly S. albidofuscus (1, 2); and Streptumyees 

 sp. (3). 



Method of extraction: I. Broth extracted with 

 butyl acetate. Extract concentrated to a syrup in 

 vacuo. Addition of ether or petroleum ether and 

 cooling gives crystals. Taken up in chloroform, 

 concentrated, and recrystallized from ethanol. 

 Can also be adsorbed on activated carlion and 

 elated with ethanol or acetone, or extracted from 

 mycelium with acetone (1, 5). II. Broth-filtrate 

 at pH 7.4 passed through a column of lonex C 

 cation exchange resin {H+ form). Column washed 

 with water and 0.5 .V HCl and eluted with 80 per 

 cent acetone. Active fractions adjusted to pH 7.4 

 and evaporated in vacuo. Residue extracted with 

 ethyl acetate. Extract concentrated and chro- 

 matographed on aluminum oxide. CoUuun washed 

 with ethyl acetate, methanol, and acetone, and 

 eluted with 80 per cent aciueous acetone. Evapora- 

 tion of the effluent gives crystals. Recrystallized 

 from acetone-water (3). 



Chenncal and physical properties: Colorless 

 needles; m.p. 221-222°C (5) or 214-216°C (3). Very 

 soluble in chloroform. Soluble in lower alcohols, 

 ethyl or l)utyl acetate, benzene, ethyl Cellosolve, 

 acetone, dioxane, and tetrahydrofuran. Slightly 

 soluble in ether and petroleum ether. Water solu- 

 bility increased by addition of HCl ; also increased 

 by alkali, but with a concomitant loss of biological 

 activity. Ultraviolet absorption spectrum maxima 

 at 303 niM (^'IL 209) (alcohol); or 227 ni/x {E^^^ 

 505) and 303 m^ (^IL 250) (0.1 X HCl) ; or 331 m^ 

 (Et'L 166) (0.1 A' NaOH) (1, 5). Infrared spectrvmi 

 given in reference 5. Positive FeChi , biuret, and 

 Rosenthaler tests. Negative ninhydrin, Benedict, 

 Fehling, and Sakaguchi tests. Stable at an acid re 

 action but not at an alkaline. No methoxyl or ace- 

 tyl groups; cannot be hydrogenated. Contains a 

 pyridine nucleus. C26--.7H32N408 : C = 60.62%; H = 

 5.95%; N = 10.37%. Hydrochloride: White needles; 

 m.p. 194-196°C (decomposition). Freely soluble in 

 water. Ultraviolet absorption spectrum ma.xima at 

 226 (EiL 669) and 303 niju (^}em 332). Infrared ab- 

 sorption spectrum given in reference 5. [q:]d = 

 — 53.2° (c = 1.0 per cent in water). Alkali fusion 

 products include |8-picoline, 2-ethyl malic acid, 

 3-hydroxypicolinic acid, glycine, and leucine or 

 isoleucine. Mild acid hydrolysis products include 

 a substance containing a pyridine nucleus, C20H22- 

 N4OC1 . Strong acid hydrolysis products include 

 L-threonine (5). 



Biological activity: Active against mycobacteria. 

 Active on K. pneumoniae (3 ng per ml), Sal. para- 

 typhi A (6 ixg per ml) , and E. coli (25 Mg pPi' nil ) , l)ut 

 not on other bacteria tested (1, 5). Slightly in- 

 hibits ascites increase in mice with Ehrlich carci- 

 noma (4). 



Toxicity: Base: Mice tolerate 1998 mg per kg 

 intraperitoneally. Hydrochloride: LD:,i) (mice) = 

 300 mg per kg intraperitoneally (5). 



References: 



1. Maeda, K. (7 al. .J. Antibiotics (Japan) 



6A: 140, 1953. 



2. Okami, Y. et al. J. Antiljiotics (Japan) 



7A: 55-56, 1954. 



3. Kiu'oya, M. et al. J. Antilnotics (Japan) 



7A: 58-59, 1954. 



4. Nitta, K. (7 al. J. Antilnotics (Japan) 8,A : 



120-125, 1955. 



5. Maeda, K. J. Antibiotics (Japan) 1(»A:94- 



106, 1957. 



6. Umezawa, H. and Okami, Y. J. Antibiotics 



(Japan) KIA: 172, 1957. 



7. Y'agishita, K. J. Antibiotics (Japan) lOA : 



5-20, 1957. 



