272 



DESCRIPTIONS OF ANTIBIOTICS 



1!)3.17, with suggested empirical formula CtHt- 

 NoOj . Infrared alisorption .spectrum given in ref- 

 erence 1. Light absorption maxima at 239, 270 to 

 280, and 340 m^ in pH 7.85 pho.sphate buffer. At 

 pH 10 the maxima at 239 and 340 m^i are destroyed 

 but the maximum at 270 to 280 m^ remain-s un- 

 changed. Neutral compound, soluV)le in practically 

 all common organic solvents except hydrocarbons. 

 Soluble in water (2 mg per ml cold; 40 mg per ml 

 hot). Destroyed by alkalies. Not affected by 6 A' 

 HCl at 100°C for 40 hours. Positive copper svUfide 

 test. Negative ninhydrin, FeCls , Tollen, Benedict 

 iodoform, biiu'et, Hinslierg, antl Sakaguchi tests 

 (1). 



Biolofiii-al activity: In vitro: Low tlegree of ac- 

 tivity against gram -positive and gram -negative 

 bacteria. Of 23 strains of bacteria tested, only 

 three were sensitive to less than 25 fxg per ml. Low 

 degree of activity against some fungi {Histoplasma 

 rapsulatuiii) and some protozoa (2). In vivo: Lim- 

 ited activity against trichomonas infections in 

 mice and hamsters. No activity in mice against 

 experimental infections caused by Streptococcus 

 hemolyticus, K. pneumoniae, Histoplasma capsula- 

 tum, and Cryptococcus neoformans (2). Inactive 

 against sarcoma 180, Ehrlich carcinoma ascites. 

 Walker adenocarcinoma, Murphy-Sturm lympho- 

 sarcoma, Jensen sarcoma, and Ouerin adenocar- 

 cinoma in mice or rats (2). 



Toxicity: LD50 (mice) 65 mg i)er kg intraperito- 

 neally; (hamsters) 11.2 mg i)er kg (2). 



References: 



1. Eble,T.E. f/o/. Antibiotics Ami. 227-229, 



1959-1960. 



2. DeBoer, C. e/ fl/. Antibiotics Ann. 220-226, 



1959-19()0. 



Filipiii 



Prtnliiccil Ijy: Streptomyces filipinensis (2, 8). 

 This culture also produces an unrelated antifungal 

 substance, which is chloroform-soluble (8). 



Method of extraction: 1. I'^thyl acetate, ether, or 

 n-butanol extracts of filtered broth evaporated to 

 ifo volume, hexane or Skellysolve B added, and 

 residting precipitate washed with petroleum ether 

 and dried in vacuo. Extracted from mycelium with 

 methanol and butanol. Crystallized by trituration 

 with chloroform and i-ecrystallized from methanol 

 (2, 8). II. Broth mixed with diatomaceous earth, 

 filtered, and broth extracted with ethyl acetate. 

 Solvent extract concentrated in vocuo, and tilijjin 

 precipitated with petroleum ether. Crystallized 

 from chloroform (3). 



Chemical and physical properties: 'i'ellow, neu- 

 tral conjugated pentaene. Fine needles. At 147°C 



undergoes transition to second, partially degraded 

 form with m.p. 195-205°C (decomposition). Very 

 soluble in dimethylformamide and pyridine. Solu- 

 ble in methanol, ethanol, n-butanol, isopropyl 

 alcohol, t -butyl alcohol, ether, ethyl acetate, amyl 

 acetate, and glacial acetic acid. Nearly insoluble 

 in water, chloroform, 50 per cent ethanol, methyl- 

 ene chloride, and Skellysolve B. X*J^°x" 322 (£'1L 

 910), 338 {E^L 1360), and 355 (£lL 1330) with a 

 shoulder at 305. No shift in acid or alkali. Infrared 

 .spectrum given in reference '3. [aln = —148.3° 

 (c = 0.89 per cent in methanol). Positive Molisch 

 test. Negative ninhydrin, biuret, Benedict, Tol- 

 len, 2,4-dinitrophenylhydrazine, and FeCls tests. 

 Deep blue color in concentrated HCl or H2SO4 , 

 Init not in HNOj . Thermolabile. Photosensitive 

 in Oj . Subject to auto-oxidation. Stable in dark 

 in air at 5°C. Seventy per cent inactivated by 10 

 per cent horse serum in a methanol solution. Rf 

 values on paper chromatography given in refer- 

 ences 2 and 3. Tentative empirical formula: 

 C32H;,40iii (11). Saponification equivalent, 574. 

 Filipin undergoes a nonreversible, autocata- 

 lytic degradation in concentrated niethanolic or 

 ethanolic solutions standing at 4°C, to a white, 

 biologically and optically inactive, crystalline 

 polyene, CsoHsoOio , m.p. 195-205°C, with an in- 

 frared spectrum nearly identical to filipin and 

 X^^ at 318 (EuL 1050), 303 (.^IL 1170), 290 (i/lL 

 770) and a sho\ilder at 281. Gives a wine-red color 

 in concentrated H2SO4 . Basic hydrolysis of filipin 

 yields a biologically inactive acid thought to be 

 derived from a lactone ring (2, 3, 10). 



Biological activity: Active on fungi and yeasts; 

 slightly active on Trichomonas foetus. Not active 

 on bacteria. Naturally occurring fungal rot of pea 

 and tomato seeds (caused by penicillia, aspergilli, 

 and phycomycetes for the most part) almost com- 

 pletely suppressed bj' soaking seeds for 3 hours in 

 25 to 100 Mg per ml of filipin. Partial protection of 

 tomato plants from gray leaf spot (Stemphyliunt 

 solani) in greenhouse tests (1, 2). Active on the 

 damping-off stage of safflower root rot (Pythium 

 sp.) (5), downy mildew of cucumber {Pseudopero- 

 nospora cubensis) (6) and broccoli (Peronospora 

 parasitica) (7), black mold of onion, corn leaf 

 blight, collar rot of tomatoe.s, bitter rot of apples, 

 and tomato wilt (8). Improves emergence of cu- 

 cumber, vegetable marrow, and muskmelon (4). 

 Activity on Penicillium oxalicum reversed by 

 cholesterol (10). Intermediate activity on sarcoma 

 180 (mice) (8). 



Toxicity: LDoo (mice) 17 mg per kg intrajieri- 

 toneally (8). No effect on pea and tomato seed 

 germination at 100 ^g per ml applied by soaking. 



