﻿CHEMOTHERAPEUTIC 
  AGENTS 
  — 
  WEINTRAUB 
  563 
  

  

  Gliotoxin. 
  — 
  An 
  antimicrobial 
  substance 
  isolated 
  in 
  crystalline 
  form 
  

   from 
  Gliocladium 
  fimbiiatum 
  has 
  been 
  given 
  the 
  name 
  "gliotoxin." 
  

   It 
  has 
  the 
  empirical 
  formula 
  CisH^CXNaSo 
  and 
  is 
  the 
  first 
  antibiotic 
  

   compound 
  of 
  microbial 
  origin 
  which 
  has 
  been 
  found 
  to 
  contain 
  sulfur. 
  

   The 
  chemical 
  structure 
  has 
  not 
  yet 
  been 
  elucidated 
  completely 
  but 
  it 
  

   appears 
  to 
  be 
  a 
  condensed 
  3-ring 
  compound 
  with 
  a 
  unique 
  type 
  of 
  

   sulfur 
  bridge. 
  Gliotoxin 
  is 
  both 
  bacteriostatic 
  and 
  bactericidal 
  

   toward 
  Gram-negative 
  as 
  well 
  as 
  Gram-positive 
  organisms. 
  Staphy- 
  

   lococci 
  and 
  streptococci 
  are 
  completely 
  inhibited 
  by 
  concentrations 
  

   of 
  the 
  order 
  of 
  0.0001 
  percent, 
  Gram-negative 
  bacteria 
  by 
  somewhat 
  

   higher 
  concentrations. 
  It 
  is 
  toxic 
  for 
  higher 
  animals 
  in 
  doses 
  of 
  50 
  

   to 
  75 
  milligrams 
  per 
  kilogram. 
  No 
  therapeutic 
  trials 
  have 
  been 
  

   reported. 
  

  

  Aspergillic 
  acid. 
  — 
  Some, 
  but 
  not 
  all, 
  strains 
  of 
  Aspergillus 
  flavus 
  

   have 
  been 
  found 
  to 
  produce 
  an 
  antibacterial 
  substance 
  which 
  has 
  

   been 
  designated 
  "aspergillic 
  acid." 
  The 
  material 
  has 
  been 
  obtained 
  

   in 
  crystalline 
  form 
  in 
  yields 
  as 
  high 
  as 
  400 
  milligrams 
  per 
  liter 
  of 
  

   culture 
  fluid. 
  The 
  empirical 
  formula 
  of 
  aspergillic 
  acid 
  appears 
  to 
  

   be 
  C12H20N0O2; 
  its 
  chemical 
  structure 
  has 
  not 
  yet 
  been 
  worked 
  out. 
  

   In 
  vitro 
  it 
  is 
  fairly 
  potent 
  against 
  certain 
  Gram-positive 
  cocci; 
  

   pneumococci 
  and 
  hemolytic 
  streptococci, 
  for 
  example, 
  are 
  killed 
  by 
  

   a 
  concentration 
  of 
  about 
  0.0002 
  percent. 
  Gram-negative 
  bacilli 
  are 
  

   much 
  more 
  resistant 
  to 
  its 
  action. 
  

  

  The 
  toxicity 
  toward 
  mice 
  is 
  not 
  especially 
  high. 
  The 
  maximal 
  

   tolerated 
  dose 
  is 
  about 
  200 
  milligrams 
  per 
  kilogram 
  when 
  given 
  orally 
  

   and 
  approximately 
  half 
  of 
  this 
  when 
  injected 
  intraperitoneally. 
  

   However, 
  neither 
  oral 
  nor 
  intraperitoneal 
  administration 
  has 
  been 
  

   found 
  to 
  exert 
  any 
  therapeutic 
  effect 
  on 
  experimental 
  mouse 
  infec- 
  

   tions 
  with 
  pneumococci 
  or 
  hemolytic 
  streptococci, 
  although 
  prelimi- 
  

   nary 
  experiments 
  have 
  shown 
  some 
  protection 
  in 
  experimental 
  

   infections 
  with 
  gonococci 
  and 
  gas 
  gangrene 
  bacilli. 
  

  

  Aspergillin. 
  — 
  This 
  name 
  has 
  been 
  given 
  to 
  an 
  antibacterial 
  sub- 
  

   stance 
  which 
  has 
  been 
  obtained 
  in 
  partially 
  purified 
  form 
  from 
  a 
  strain 
  

   of 
  Aspergillus 
  flavus. 
  What 
  relation 
  this 
  material 
  may 
  have 
  to 
  other 
  

   antibacterial 
  agents 
  of 
  microbial 
  origin 
  cannot 
  be 
  determined 
  from 
  

   the 
  limited 
  information 
  so 
  far 
  available. 
  Making 
  allowances 
  for 
  the 
  

   impure 
  state 
  of 
  the 
  aspergillin 
  tested, 
  its 
  bacteriostatic 
  potency 
  and 
  

   toxicity 
  appear 
  to 
  correspond 
  approximately 
  with 
  those 
  of 
  aspergillic 
  

   acid. 
  

  

  Puberulic 
  and 
  puberulonic 
  acids. 
  — 
  These 
  substances 
  have 
  been 
  iso- 
  

   lated 
  in 
  crystalline 
  form 
  as 
  metabolic 
  products 
  of 
  several 
  species 
  of 
  

   Penicillium. 
  The 
  empirical 
  formulas 
  are 
  C 
  8 
  H 
  6 
  6 
  and 
  CsH 
  4 
  6 
  , 
  re- 
  

   spectively. 
  The 
  chemical 
  constitution 
  is 
  unknown, 
  but 
  puberulonic 
  

  

  