DESCRIPTIONS OF ANTIBIOTICS 



J41 



15. Brockmami, H. and O.ster, R. Cheni. Ber. 



90:605-617, 1957. 



16. Anliker, R. and Guhler, K. Helv. Chim. 



Acta M): 119-129, 1957. 



17. Anliker, R. and Gul)ler, K. Helv. Chim. 



Acta 10: 1768-1772, 1957. 



Pima ric ill 



Produced by: Streptoniyces tiatalensis. 



Method of extraction: E.xtraction of mycelium 

 with lower alcohols, glycols, or formamide and its 

 derivatives. Partial evaporation of such extracts 

 followed by addition of water gives a crystalline 

 precipitate (pimaricin). Further purification by 

 recrystallization from hot methanol, or by reisola- 

 tion from its organic or inorganic salt.s (1). 



Chemical and physical properties: Tetraenic 

 macrolide. Colorless. Decomposes at about 200°C. 

 Soluble in methylpyrrolidone, methyl Cellosolve 

 plus 2 percent CaCh , and dilute acids and alkalies. 

 Slightly soluble in methanol, propylene glycol, 

 diethylene glycol, and formamide. Practically 

 insoluble in water. X„iax 279, 290, 303, and 318. 

 [ajo = +250°. Positive tests for primary amino 

 groups (Van Slyke), carboxyl, and keto groups. 

 Positive iodoform test in acjueous bicarbonate 

 solution. Stable when dry or in solution at pH 5 

 to 7 in water. Photosensitive, subject to autoxida- 

 tion, relatively thermostable. Na-K chlorophyllin 

 and other substances which strongly absorb 

 ultraviolet light in the range of 300 to 400 m^i 

 prevent loss of activity of pimaricin in ultraviolet 

 light and in the air (5). C34H49NO14: C = 58.53 

 ±0.32%; H = 7.32 ± 0.17%; N = 2.12 ± 0.14%; 

 C— CH3 = 1.43%. Hydrolysis with methanolic 

 HCl gives mycosamine. Alkaline hydroI^^sis gives 

 13-hydroxy-2,4,0,8,10-tetradecapentaeneal. This 

 compound has the following characteristics : orange 

 crystals; m.p. 124-128°C. Ultraviolet absorption 

 spectrum maximiun at 375 m/i (methanol) . Positive 

 Fehling test (1, 3, 4). Complete structure of 

 pimaricin given in Chapter 6. Xasalt: More water- 

 soluble than pimaricin (5). 



Biological activity: Active on fungi and yeasts, 

 both pathogenic and saprophytic. Active on 

 Trichomonas vaginalis. Fungicidal. Active over a 

 wide pH range. Suppresses intestinal overgrowth 

 by yeasts after tetracycline administration in 

 rats and mice (2) . 



Toxicity: LD^n (rat) 1500 mg per kg orally, 650 

 mg per kgintraperitoneally, 2000 mg per kg intra- 

 muscularly, and 5000 mg per kg subcutaneously. 

 LD50 (mice) 1500 mg per kg orally. LD50 (guinea 

 pig) 450 mg per kg orally. No toxic effects on rats 

 fed 50 to 70 mg per kg for 5 to 10 weeks, but 150 

 mg per kg inhibit growth. 



References: 



1. Struyk, A. P. et al. Antibiotics Ann. 878- 



885, 1957-1958. 



2. ]\Ianten, A. and Hoogerheide, J. C. Anti- 



biotics & Chemotherapy 8: 381-386, 1958. 



3. Patrick, J. B. et al. J. Am. Chem. Soc. 80: 



6688-6689, 1958. 



4. Dutch Patent 87,323, January 15, 1958. 



5. Dekker, J. and Ark, P. A. Antibiotics & 



Chemot herapy 9 : 327-332 , 1959 . 



Pleocidins 



Produced liy: Streptoniyccs sp. reseml)ling »S. 

 lavendidac (1). 



Synonyms: Streptothricin-like anti!)iotic. Pleo- 

 cidin I appears to l:)e streptothricin (see belowj 

 (3). See also streptothricin-like antibiotics. 



Method of extraction: I. Extracted like strepto- 

 thricin. II. Brothtreated with oxalate to remove 

 Ca++ ions, then adsorbed on IRC-50 at pH 8.0 and 

 eluted with 10 per cent aqueous HCl. Freed of 

 excess acid by passage over IR4B, then lyo- 

 philized. Purified by helianthate cyclization (1). 

 III. Puritication of the complex by chromatog- 

 raphy on Darco G-60-Hyflo Super-Cel (1:2) from 

 aqueous solution. Developed first with distilled 

 water to give Fraction A, then with methanol-1 

 X HCl-water (15:2:8) to give B. Rf values of the 

 components contained in Fractions A and B will 

 be found in Table 43 under "streptothricin-like 

 antibiotics." Lyophilized fractions taken up in 

 methanol and precipitated with acetone. Complex 

 further resolved by chromatography on cellulose 

 with water as solvent and 1-propanol-pyridine- 

 acetic acid-water (15:10:3:12) as developer. Ether 

 added to the effluent fractions, and the antibiotic- 

 containing lower phases lyophilized. Pleocidin I 



T.\BLB 42 

 Biological activity of pleocidins (Horowitz, 1957) 



Antibiotic 



Pleocidin complex... 



Pleocidin I 



Streptothricin (com 

 mercial) 



Pleocidin II 



Pleocidin III 



Pleocidin IV 



Minimum inhibitory concentration 





fig/ml 



1.3 

 0.55 



0.55 

 0.83 

 1.4 

 1.4 



5.0 

 67 



67 

 3.7 



7.7 

 20 



