DESCRIPTIONS OF ANTIBIOTICS 



303 



inycin, and antibiotic 129, a synergistic relation- 

 ship was found between mikamycins A and B {2). 



Method of extraction: Extraction of l)roth-filtrate 

 with ethyl acetate. Concentration of the ethyl 

 acetate extract under vacuum to '20 vohune. A 

 I)recipitate forms which contains 48 per cent 

 mikamycin A and 6.5 per cent mikamycin B. Addi- 

 tion of 10 volumes of petroleum ether to the super- 

 natant gives a syrup containing 13 per cent mika- 

 mycin A and 18 per cent mikamycin B. Syrup 

 dissolved in methanol; addition of ether causes 

 formation of a precipitate, which is dried in vacuo. 

 Resulting powder dissolved in benzene and chro- 

 matographed over silicic acid. Cohmm washed 

 with chloroform, and elution carried out with 

 chloroform containing 5 per cent acetone. Frac- 

 tions of the eluate containing only mikamycin B 

 (Rf = 0.05, ascending paper chromatography with 

 3 per cent ammonium chloride) combined and con- 

 centrated to a syrup in vacuo. Syrup treated with 

 ether. A white insoluble powder contains 72 per 

 cent mikamycin B and less than 1 per cent mika- 

 mycin A. This powder extracted with ether in a 

 Soxhlet apparatus. Crude crystals of mikamycin 

 B precipitated from the ether solution. Recrystal- 

 lized from methanol. 



Chemical and physical properties: Amj)hoteric, 

 white, platelet -shajjed crystals, which melt at 

 160°C, solidify above 180°C, and decompose at 

 262°C. [aln = -61.3° (c = 1.0 per cent in meth- 

 anol). Molecular weight (Signer), 865. C = 60%; 

 H = 6.43%; N = 12.53%. Suggested empirical 

 formula: C45H58Ns()ii . Light-absorption maxima 

 at 209, 260, and 305 m/i in methanol. Infrared al)- 

 sorption spectrum given in reference 1. Soluble in 

 chloroform, acetone, methyl isobutyl ketone, 

 l)enzene, ethyl acetate, ethanol, and methanol. 

 Slightly soluble to insoluble in ether, cyclohexane, 

 petroleum ether, and water. Salts are solul)le in 

 water. Positive FeCl.'i (brown-red) test. Mikamy- 

 cin A gives a dark green FeCls test. Almost nega- 

 tive ninhydrin reaction. Negative Ehrlich, biuret, 

 Fehling, and Tollen reactions. Stable at neutral 

 and acidic reactions (1). 



Mikamycin is a macrocyclic peptide lactone 

 composed of the following seven amino acids: 3- 

 hydroxypicolinic acid, L-threonine, D-a-amino-«- 

 Ijutyric acid, L-proline, L-phenylglycine, L-4-oxo- 

 pipecolic acid, and L-p-dimethyl amino-N-methyl- 

 phenylalanine. This last amino acid had not been 

 l)reviously reported (4). The structure given in 

 reference (5) is closely related to those of etamycin 

 and staphylomycin S. 



Biological activity: Active against gram-positive 

 bacteria. Mikamycins A and B have synergistic 



activity in vitro and in vivo when there is 10 to 90 

 per cent of mikamycin B in the mixture (2). Mika- 

 mycin B inhibits Staph, aureus at 8 fxg per ml (A 

 at 2yug per ml ) ; mikamycin A inhibits Sarcina lutea 

 at 0.25 fjLg per ml (B at 4 /xg per ml) ; B. subtilis is 

 inhibited by mikamycin A at >64 ng per ml (B 

 at 8 ng per ml). Staph. a>n-eus exposed to mika- 

 mycin B becomes more sensitive to A, but the 

 reverse is not true (3). 



Toxicity: Mice tolerate 350 ng per ml intraperi- 

 toneally (3). 



References: 



1. Watanabe, K. J. Antiiiiotics (Japan) 13A: 



57-61 , 1960. 



2. Watanabe, K. J. Antibiotics (.Japan) I3A: 



62-69, 1960. 



3. Watanabe, K. et al. J. Antibiotics (Japan) 



12A: 112-113, 1959. 



4. Watanabe, K. J. Antibiotics (Japan) 14A: 



1-13, 1961. 



5. Watanabe, K. J. Antibiotics (Japan) 14A: 



14-17, 1961. 



Miranij cin 



Produced by: Strcptoniyces niirabilis. 



Method of extraction: Unknown. Culture-broths 

 contain more than one antibiotic. 



Chemical and physical properties: Heat -stable. 



Biological activity: Active against gram -posi- 

 tive and gram-negative bacteria. 



Toxicity: Said to be nontoxic. 



References: 



1. Ruschmann, (I. Pharmazie 7:542-550,639- 



648, 823-831, 1952. 



2. BcungJ. Pharmazie 13:305 310,1958. 



M il<>ni\ cins 



Produced by: Streplomyces caespitosus (2, 9) and 

 S. griseovinaceseus (3). 



Remarks: In the hands of one group of investi- 

 gators (9), S. caespitosus produced a complex 

 differing somewhat from that originally described 

 (1). Further fractions other than those described 

 below have been reported, i)ut no details are 

 known (12). 



Methods of extraction: Original description: Fil- 

 tered broth treated with activated carbon at 

 pH 6.0 to 6.5. Eluted with acetone. Acetone con- 

 centrated in vacuo and the residue extracted 

 with chloroform (I). Purple-red chloroform ex- 

 tract dehydrated with anhydrous Na2S()4 aiul 

 chromatographed on alumina. Colored fractions 

 included: yellow, blue-violet, pink and l)Iue, red- 

 violet, and purple. The latter two, mitomycins 

 A ami B, eluted with methanol or water. Puri- 



