CHEMICAL NATURE OF ANTIBIOTICS 



61 



Echinomijcin is an antibacterial antibiotic 

 containing two fjuinoxaline moieties: 



N 



These are attached to a polypeptide moiety. 



Phenoxaziiies: The Actinom veins 



The actinom ijcins are red-colored anti- 

 biotics, the molecules of which consist of a 

 phenoxazine nucleus to which are attached 

 two polypeptide chains. These antibiotics 

 are active against gram-positive bacteria 

 and tumors. Actinomycins are usually pro- 

 duced by actinomycetes as mixtures of 

 closely related compounds which all have 

 the same phenoxazine chromophore but 

 which differ in the amino acid composition 

 of the polypeptide chains. Qnestiomycin A 

 ((3-aminophenoxazone) is active mainly 

 against mycobacteria : 



NHo 



This rather nontoxic compound is closely 

 related to the chromophore of the actino- 

 mycins. It is believed to be formed by the 

 condensation of two molecules of (juestio- 

 mycin B (o-aminophenol). 



The chromophore of the actinomycins 

 is 3-amino-l ,8-dimethylphenoxazone-(2)-di- 

 carboxylic acid- (4, 5): 



CO OH CO OH 



N 



NH, 



CHs 



CH3 



In the molecules of the actinomycins, two 

 cyclic five-membered polypeptides are linked 

 to the carboxyl groups. Their composition 

 varies from one actinomycin to the other, 

 as explained in Part B of this book. 



The opening by alkali treatment of the 

 polypeptide rings produces actinomycinic 

 acids which have no antibacterial activity 

 but some antitumor activities. 



Some antibiotics other than the actino- 

 mycins are also polypeptides with an aro- 

 matic chromophore. They include Icvomycin, 

 mikamycin A , actinoleukin, and as previously 

 ment ioned , cchin om ycin . 



Oligojieptides 



A group of closely related substances, the 

 antimycins and blastmycin, have antifungal 

 activity and inhibit electron transport in 

 cytochrome systems. Their molecule is 

 composed of two large moieties, antimycic 

 acid and a neutral fragment. Antimycic 

 acid itself contains two moieties: (1) L-thre- 

 onine, and (2) a substituted salicylic acid 

 fragment. The neutral fragment is composed 

 of a variously substituted furan ring. The 

 following structure has been suggested for 

 these compounds: 



I O, 



NH 



CHO 



— CO- 

 — OH 



-NH- 



CO— O- 



I 



-CH 



I 

 CHOH 



I 

 CH3 



-R 



R. 



Aiitimvcic acid 



O 



CO 



I 

 R2 



Neutral 

 fragment 



Blastmycin: R = CH,, ; R, = (CH.JsCHs ; 



R2 = CH2— CH(CH3).> 

 Antimvcin.s: R = C7H16 ; Ri = H; 



R2 = CHCH-CH3 



I 



CH:, 



The various antimycins (there are at least 

 four) probal)ly differ in the structiu'e of the 

 C7H15 fragment. 



A recent paper (Strong et al., 1960) has 

 modified the concept of the structure of the 

 antimycins. The substituted salicylic acid 

 fragment, present in antimycic acid, is 

 attached to a dilactonic ring. 



