l)i:SC'HIPTI()XS OF AXTIlilOTICS 



285 



solvents is iiKTeased by aciilific;itioii. IhsoIuIjIc in 

 wiiter unless strong alkalies are added; then it 

 gives a red color. Very stable except in aqueous 

 ail<aline solutions, such as 0.1 A' NaOH. Xo melt- 

 ing point; vipon heating over 100°C, it decomposes. 

 Molecular weight, 235 (Rast). Positive Millon, 

 sodium nitrite, and sodium nitr()])russide tests. 

 i'ositive Anchel test for i^henols and ciuinones. Xo 

 reduction of Fehling's reagent. Contains no X', S, 

 or P. Ala.ximal absorption of light at 2()9, 290, 320, 

 340, 370, 400, and 515 m/x (alcoholic solution). 

 Alkaline degradation is accompanied by changes 

 in light -absorption spectrum (given in reference 

 4). 



liioloijii-dl tutivilij: Active on staphylococci and 

 iuHuenza virus (contact test). Slight activity on 

 influenza in mice (1). Active on tobacco mosaic 

 virus it\ vitro (2) and smalljjox vaccine (4). B. 

 injicoidcx used as assay organism (5). 



Toxicity: LDso (mice) 25 mg jx'r kg intraperi- 

 toneally (6). 



References: 



1. Gause, G. F. Giorn. mici()l>iol. 2: l!)4-200, 



1950. 



2. Ukholina, R. S. Mikrobiologiya 27: 347- 



350, 1958. 



3. Brajhnikova, M. (i. et at. 2n(l All-Union 



Conf. Antibiotics, Moscow, p. 9, 1957. 



4. Kremer, V. E. Antibiotiki 4(6) : 59-(J3, 1959. 



5. Brajhnikova, M. G. c/ «/.. Antibiotiki 3(2): 



29-34, 1958. 

 0. Goldberg, L. E. Antil)i()tiki 5(1): 107-112, 

 19()(). 



Holoniycin 



Frodticcd by: Streptomi/ces griseus. 



Si/iiohijin: Belongs to the thiolutin aureothricin 

 series, differing from thiolutin oidy in the X — CHs 

 group. 



Method of extraction: Broth-filtrate extracted 

 with ethyl acetate. E.xtract concentrated in vacuo. 

 Ghromatographed on aluminum oxide, washed 

 with absolute chloroform anfl chloroform metha- 

 nol (99:1), and eluted with chloroform-nu>t haiiol 

 (,97:3). Active fractions concentrated in vacuo to 

 an oily residue. Residue taken up in ethyl acetate; 

 the antibiotic precipitates after a short time. Re- 

 crystallized from methanol-ethyl acetate. 



Chemical and physical properties: Des -X"^ -methyl - 

 thiolutin. X'eutral. Glittering orange-yellow 

 rhomi)ic crystals; m.p. 2G4-271°C (mixed melting 

 point with thiolutin, 240-250°C). Could be sub- 

 limed in vdciio. Soluble in organic solvents. Ultra- 

 violet absorption spectrum maxima (ethanol) at 

 about 390 m^x, with lesser peaks at about 303 and 

 250 mjj.. Infrared spectriuu given in reference 1. 



Paper chr()nia(ograi)liic data given in reference 1. 

 C7H602X,S, : C = 39.25%; H = 2.79%; X = 

 13.07%; S = 29.77%; C— CH, = 7.04%; CH.CO = 

 21.38%. .\cid hydrolysis product is "holothin," 

 C5H40Xi or des-X'-methylpyrrothine. Structural 

 formula of holoniycin given in Chapter G. 



Biological oi-tivity: .\ctive on Streptococcus 

 pyogenes (1 ^g per ml), 1'. chidcrae, M . tuberculosis, 

 E. coli, Sal. schiilltuucllcn, and Klebsiella (10 yug 

 per m\); Staph, aurcu.^, Ps. aeruginosa, ('. albicans, 

 and Endouiyccs albicans (101 fxg per ml). Active on 

 Trichomonas foetu.K at 1 ^ug per ml and Endamoeba 

 histolytica at 10 /xg per nd. Holothin has some 

 antil)iotic activity. 



Reference: 1. Ettlinger, L. et al. Helv. Chim. 

 Acta 42: 563-569, 1959. 



il 



iiniKlii 



Produced by: Strcptoniyccs huuiidus, the strain 

 that also produces dihydrostreptomycin. 



Method of extraction: Cells extracted with ace- 

 tone. Concentration of solvent under reduced 

 pressure. Aqueous concentrate acidified with HCl 

 aiul extracted with ethyl acetate. Back-extraction 

 with 1 A' XaOH. Upon neutralizatioji, crystalliza- 

 tion occurs. 



Chemical ami physical properties: Colorless 

 platel(>ts; m.]). 145 14()°C. Tentative empirical 

 formula: {CvM-ni()i)„ ■ (a)i,'' = —6° (c = 1 i)er cent 

 in ethanol). [a]'v = —10° (c = 1 per cent in ace- 

 tone) and —8° (c = 1 per cent in dioxane). Light- 

 absorption maxinui at about 245 and 285 m/x. 

 Infrared absorjjtion sj)ectruni given in reference 1. 

 Soluble in acetone, dioxane, ami ethyl acetate. 

 Slightly soluble in n-butyl alcohol, ether, and 

 ethanol. Insoluble in methanol, benzene, water, 

 petroleum ether, and carbon tetrachloride. Orange 

 color with sulfuiic acid. Potassium permanganate 

 and bromine water decohji'ized. Xegative Fehling 

 reaction. 



Biological activity: Active against certain fungi 

 and protozoa. Xo activity against bacteria. Active 

 against Sacch. cerevisiae but not against species of 

 Candida. More active at alkaline than at acid jjH. 

 Activity reduced by ascorbic acid but not l)y 

 cysteine. 



Toxicity: LD50 (mice) 4.5 mg jjer kg intrajieri- 

 toneally, 54 mg per kg orally. 



Reference: 1. Xakazawa, K. et al. J. Agr. Chem. 

 Soc. Japan 32: 713-716, 1958. 



Ilv<i 



i'ox\ iii\ cm 



Produced by: Streptomyces paucisporogenes (2). 

 Synonyms: Antibiotic 4915 (2). Similar to cate- 

 nulin and ]iai'()momycin (4). 



Method of cxtna-tion: Cultiu'e-filtrate adjusted 



