210 



DESCRIPTIONS OF ANTIBIOTICS 



tetrachloride. Insoluble in water, 5 per cent HCl, 

 and 5 per cent NaHCOg (3, 12, 15, 17 j. Ultraviolet 

 absorption spectrum maxima at about 225 to 228 

 and 320 to 330. Bathochromic shift on addition of 

 base. Infrared spectrum (the same for all com- 

 ponents isolated) given in references 12 and 24. 

 Positive hydroxamic, Millon, FeCU , Gibbs diazo, 

 Liebermann's nitroso, and KMn04 tests. No color 

 in concentrated H2SO4 - Negative Molisch, nin- 

 hydrin, Ehrlich, fuchsin aldehyde, 2,4-dinitro- 

 phenylhydrazine, chromotropic acid, pine splint, 

 and cyanogen bromide tests (3, 12, 17). Stable at 

 room temperature. Photosensitive (23). Mild alka- 

 line hydrolysis yields, among other products, 

 antimycic acid (CuHuOoN^) and N-(3-amino- 

 salicyloyl)-L-threonine (12, 13). Hydrolysis prod- 

 ucts also include a neutral, stable, colorless, pleas- 

 ant-smelling, water-insoluble oil, C16H28O4 (26), 

 believed to be: 



CH3O R' R" 



I II 

 CHsCHC— O- 



R 



Individual components of the antimycin com- 

 plexes all contain the antimycic acid residue, but 

 differ in the nature of the substitution in the neu- 

 tral fragment above (i.e., R, R', and R" = H or 

 alkyl group) (28). Two different structures have 

 been proposed for "antimycin," but for which 

 antimycin component is not clear (20, 26). One 

 complex (A 35) has been separated into five frac- 

 tions: Ai , A-2a , A-2b , A3 , and a minor fraction, 

 A4 (23). Another (A 102) contained almost 60 per 

 cent A3 , in addition to A, , A. , and A4 (15, 23). 

 Another complex was shown to contain the same 

 components as A 102 (24). Rf values of these vari- 

 ous components on paper chromatography in 

 different systems are given in references 23 and 24. 

 Antimycin A, : m.p. 149-150°C (23) or 147-148°C 

 (24). [a]u = +74.0° (in chloroform). C = 61.11%; 

 H = 7.32%; N = 5.03S7c. C28H4nNo09 (23, 24). 

 Antimycin A-2x '■ m.p. 147-148°C. C26H34O9N2. 

 Antimycin A^h : m.p. 168°C. C25H30O9N2 (23). 

 Antimycin A,, m.p. 170.5-171.5°C (23) or 167- 

 168°C. [aJD = +84.0° (in chloroform). C = 60.03%,; 

 H = 6.93%; N = 5.33%. C26H36N2O9 (23, 24). 



Biological activity: Active against yeasts and 

 filamentous fungi. Very little activity against bac- 

 teria (1). Inhibits influenza virus in tissue culture 

 by action of the host tissue cells (8) or by direct 

 inactivation of the virus (21). Slightly active on 

 RC mammary carcinoma in mice (22). Selectively 

 inhibits an electron transport component acting 

 between succinic dehydrogenase and cytochrome 



C in the succinoxidase system, and between di- 

 aphorase and cytochrome C in diphosphopyridine 

 nucleotide systems (4, 5, 9, 11). Partially inhibits 

 O2 uptake in diphosphopyridine nucleotide- 

 coupled oxidation of malate and D-glyceraldehyde 

 3-phosphate in certain organs (14). Some protec- 

 tive action on apple scab and tomato early blight 

 (2), Helminthosporium seedling blight of oats 

 (15), and rice blast {Piricidana oryzae) (17, 19). 



Toxicity: Complexes A 35 and A 102: LD50 (mice) 

 0.9 mg per kg intravenously, 7.6 mg per kg intra- 

 peritoneally, and 25 mg i)er kg subcutaneously 

 (15, 26). LD50 (rats) 0.81 mg per kg intraperi- 

 toneally. LDo (rats) 12 mg per kg, and LDioo (rats) 

 30 mg per kg orally (11, 15). Toxic to certain in- 

 sects and spiders (6, 7). Not toxic to a variety of 

 plants when applied as a spray (100 units per ml) 

 (2). Greatest phytoto.xicity in most rapidly grow- 

 ing parts of plant, and most toxic in oil solution 

 (15). 



Utilization: Useful in elucidation of metabolic 

 processes. 



References: 



1. Leben, C. and Keitt, G. W. Phytopath- 



ology 38: 899-906, 1948. 



2. Leben^ C. and Keitt, G. W. Phytopath- 



ology 39: 529-540, 1949. 



3. Dunshee, B. R. e/ «/. J. Am. Chem. Soc. 



71: 2436-2437, 1949. 



4. Ahmad, K. et al. Federation Proc. 8: 178, 



1949. 



5. Ahmad, K. et al. Arch. Biochem. 28: 



281-294, 1950. 



6. Kido, G. S. and Spyhalski, E. Science 



112: 172-173, 1950. 



7. Beck, S. D. J. Econ. Entomol. 43: 105, 



1950. 



8. Ackerman, W. W. J. Biol. Chem. 189: 



421-428, 1951. 



9. Potter, V. R. and Reif, A. E. J. Biol. Chem. 



194: 287-297, 1952. 



10. Schneider, H. G. et al. Arch. Biochem. 



Biophys. 37:147-157,1952. 



11. Reif, A. E. and Potter, V. R. Cancer Re- 



search 13: 49-57, 1953. 



12. Tener, G. M. et al. J. Am. Chem. Soc. 



75: 1100-1104, 1953. 



13. Tener, G. M. et al. J. Am. Chem. Soc. 



75: 3623-3625, 1953. 



14. Reif, A. E. and Potter, V. R. Arch. Bio- 



chem. Biophys. 48: 1-6, 1954. 



15. Lockwood, J. L. et al. Phytopathology 



44: 438-446, 1954. 



16. Leben, C. and Keitt, G. W. Antibiotics & 



Chemotherapy 6: 191-193, 1956. 



