﻿CHEMOTHERAPEUTIC 
  AGENTS 
  — 
  WEINTRAUB 
  555 
  

  

  The 
  role 
  of 
  the 
  actinomycete 
  cells 
  is 
  visualized 
  as 
  that 
  of 
  freeing 
  the 
  

   bactericidal 
  agent 
  from 
  its 
  hypothetical 
  inactive 
  complex. 
  Evidence 
  

   for 
  the 
  tendency 
  of 
  the 
  bactericidal 
  substance 
  to 
  form 
  such 
  com- 
  

   plexes 
  is 
  considered 
  to 
  be 
  furnished 
  by 
  the 
  finding 
  that 
  the 
  bacteri- 
  

   cidal 
  potency 
  is 
  much 
  less 
  in 
  complex 
  media 
  than 
  in 
  solutions 
  of 
  

   inorganic 
  salts. 
  

  

  While 
  information 
  on 
  the 
  chemical 
  nature 
  of 
  the 
  active 
  agent 
  is 
  

   still 
  very 
  fragmentary, 
  it 
  is 
  thought 
  by 
  some 
  workers 
  to 
  be 
  a 
  fatty 
  

   acid. 
  This 
  is 
  very 
  suggestive 
  of 
  a 
  parallel 
  with 
  the 
  agents 
  of 
  Bacillus 
  

   mesentericus 
  and 
  of 
  the 
  pyocyanic 
  acid 
  of 
  Pseudomonas 
  ae?-uginosa. 
  

   At 
  least 
  one 
  pigment 
  with 
  antibacterial 
  activity 
  has 
  also 
  been 
  isolated 
  

   from 
  another 
  species 
  of 
  actinomycete, 
  although 
  most 
  of 
  the 
  pig- 
  

   ments 
  produced 
  by 
  this 
  group 
  of 
  organisms 
  do 
  not 
  appear 
  to 
  have 
  

   such 
  activity. 
  

  

  No 
  direct 
  therapeutic 
  use 
  of 
  actinomycetin 
  has 
  been 
  made; 
  it 
  has 
  

   been 
  found, 
  however, 
  that 
  the 
  actinomycete-produced 
  lysates 
  of 
  a 
  

   number 
  of 
  pathogenic 
  bacteria 
  are 
  very 
  good 
  antigens 
  and 
  much 
  less 
  

   toxic 
  than 
  the 
  organisms 
  themselves. 
  Favorable 
  results 
  in 
  a 
  number 
  

   of 
  cases 
  of 
  various 
  infections 
  in 
  man 
  have 
  been 
  claimed 
  through 
  the 
  

   use 
  of 
  such 
  lysates. 
  

  

  Actinomycins 
  A 
  and 
  B. 
  — 
  From 
  cultures 
  of 
  another 
  actinomycete, 
  

   Actinomyces 
  antibioticus, 
  there 
  has 
  been 
  obtained 
  a 
  strongly 
  anti- 
  

   bacterial 
  preparation 
  which 
  was 
  termed 
  "actinomycin." 
  Subse- 
  

   quently 
  this 
  material 
  was 
  separated 
  into 
  two 
  components, 
  both 
  of 
  

   which 
  exhibited 
  activity. 
  These 
  have 
  been 
  designated 
  "actinomycin 
  

   A" 
  and 
  "actinomycin 
  B." 
  Both 
  substances 
  have 
  been 
  obtained 
  in 
  

   crystalline 
  form. 
  

  

  Actinomycin 
  A, 
  which 
  is 
  a 
  bright 
  red 
  pigment, 
  has 
  been 
  studied 
  

   chemically 
  to 
  some 
  extent. 
  Its 
  structure 
  is 
  not 
  yet 
  known 
  but 
  it 
  

   appears 
  to 
  be 
  a 
  poly 
  cyclic 
  nitrogen 
  compound 
  ; 
  possible 
  formulas 
  are 
  

   CiiHgsNgOn 
  and 
  C 
  3 
  7H 
  5 
  oN 
  7 
  Oio. 
  The 
  compound 
  has 
  a 
  high 
  degree 
  of 
  

   antibacterial 
  activity 
  which, 
  for 
  a 
  given 
  organism, 
  may 
  be 
  bacterio- 
  

   static 
  or 
  bactericidal, 
  depending 
  upon 
  the 
  concentration 
  and 
  time 
  of 
  

   action. 
  Gram-positive 
  organisms 
  are 
  considerably 
  more 
  susceptible 
  

   than 
  the 
  Gram-negative 
  forms. 
  Among 
  the 
  susceptible 
  bacteria 
  are 
  

   streptococci 
  and 
  staphylococci, 
  which 
  are 
  inhibited 
  completely 
  by 
  con- 
  

   centrations 
  of 
  0.00001 
  percent 
  ; 
  the 
  gas 
  gangrene 
  bacillus, 
  inhibited 
  by 
  

   0.0001 
  percent; 
  and 
  the 
  tubercle 
  bacillus, 
  inhibited 
  by 
  0.001 
  percent. 
  

   The 
  mechanism 
  of 
  the 
  killing 
  effect 
  by 
  higher 
  concentrations 
  appears 
  

   to 
  be 
  a 
  chemical 
  interaction 
  similar 
  to 
  that 
  of 
  the 
  common 
  antiseptics. 
  

  

  Unfortunately 
  actinomycin 
  A 
  is 
  exceedingly 
  toxic, 
  so 
  that 
  its 
  internal 
  

   administration 
  is 
  precluded. 
  Whether 
  it 
  would 
  be 
  useful 
  in 
  surface 
  

   application 
  remains 
  to 
  be 
  determined. 
  

  

  Actinomycin 
  B 
  has 
  been 
  studied 
  to 
  only 
  a 
  limited 
  extent. 
  No 
  in- 
  

   formation 
  as 
  to 
  its 
  chemical 
  nature 
  is 
  yet 
  available. 
  Some 
  difficulties 
  

  

  