﻿CHEMOTHERAPEUTIC 
  AGENTS 
  — 
  WEINTRAUB 
  561 
  

  

  Notatin, 
  penatin, 
  penicillin 
  B. 
  — 
  From 
  several 
  laboratories 
  has 
  come 
  

   evidence 
  that 
  certain 
  strains 
  of 
  Penicillium 
  notatum 
  produce, 
  in 
  addi- 
  

   tion 
  to 
  penicillin, 
  another 
  antibacterial 
  substance. 
  Various 
  investiga- 
  

   tors, 
  working 
  simultaneously 
  but 
  independently, 
  have 
  proposed 
  

   different 
  names 
  for 
  their 
  preparations: 
  "notatin," 
  "penatin," 
  "peni- 
  

   cillin 
  B"; 
  the 
  available 
  evidence, 
  while 
  not 
  entirely 
  conclusive, 
  sug- 
  

   gests 
  that 
  the 
  active 
  principle 
  is 
  the 
  same. 
  

  

  It 
  is 
  the 
  most 
  potent 
  natural 
  antibiotic 
  substance 
  so 
  far 
  described. 
  

   The 
  growth 
  of 
  Staphylococcus 
  aureus, 
  which 
  is 
  one 
  of 
  the 
  most 
  

   susceptible 
  species, 
  is 
  inhibited 
  by 
  concentrations 
  as 
  low 
  as 
  0.00000002 
  

   percent. 
  It 
  is 
  active 
  against 
  a 
  large 
  number 
  of 
  both 
  Gram-negative 
  

   and 
  Gram-positive 
  bacteria. 
  The 
  substance 
  is 
  bactericidal, 
  as 
  well 
  

   as 
  bacteriostatic, 
  but 
  does 
  not 
  appear 
  to 
  cause 
  lysis. 
  

  

  The 
  available 
  evidence 
  indicates 
  that 
  notatin 
  is 
  a 
  flavoprotein 
  in 
  

   which 
  the 
  protein 
  is 
  combined 
  with 
  flavine 
  adenine 
  dinucleotide. 
  It 
  

   functions 
  as 
  an 
  enzyme 
  which 
  catalyzes 
  the 
  oxidation 
  of 
  glucose 
  by 
  

   oxygen, 
  with 
  the 
  production 
  of 
  gluconic 
  acid 
  and 
  hydrogen 
  peroxide. 
  

   Certain 
  other 
  sugars 
  are 
  oxidized 
  also. 
  It 
  is 
  believed 
  that 
  the 
  anti- 
  

   bacterial 
  action 
  is 
  due 
  to 
  the 
  hydrogen 
  peroxide 
  formed. 
  Support 
  

   for 
  this 
  view 
  is 
  furnished 
  by 
  the 
  fact 
  that 
  the 
  activity 
  is 
  appreciable 
  

   only 
  in 
  the 
  presence 
  of 
  oxygen 
  and 
  glucose 
  and 
  in 
  the 
  absence 
  of 
  

   catalase, 
  the 
  enzyme 
  which 
  promotes 
  the 
  destruction 
  of 
  hydrogen 
  

   peroxide. 
  The 
  activity 
  is 
  reduced 
  in 
  the 
  presence 
  of 
  fresh 
  serum, 
  

   owing, 
  presumably, 
  to 
  its 
  content 
  of 
  catalase. 
  

  

  Inasmuch 
  as 
  the 
  active 
  agents 
  have 
  not 
  been 
  freed 
  from 
  impurities, 
  

   the 
  toxicity 
  cannot 
  be 
  determined 
  with 
  certainty. 
  Some 
  preparations 
  

   have 
  been 
  found 
  to 
  be 
  rather 
  toxic, 
  others 
  much 
  less 
  so. 
  No 
  detailed 
  

   information 
  as 
  to 
  the 
  therapeutic 
  applicability 
  of 
  the 
  substance 
  is 
  yet 
  

   available, 
  although 
  notatin 
  has 
  been 
  reported 
  as 
  having 
  been 
  found 
  

   effective 
  in 
  this 
  respect. 
  

  

  Penicillic 
  acid. 
  — 
  This 
  substance, 
  which 
  is 
  not 
  related 
  to 
  penicillin, 
  

   despite 
  the 
  similarity 
  of 
  names, 
  was 
  isolated 
  from 
  Penicillium 
  puber- 
  

   ulum 
  in 
  1911, 
  at 
  which 
  time 
  it 
  was 
  found 
  to 
  have 
  an 
  inhibitory 
  effect 
  

   upon 
  the 
  growth 
  of 
  certain 
  bacteria. 
  Interest 
  in 
  the 
  substance 
  was 
  

   revived 
  in 
  recent 
  years 
  by 
  the 
  discovery 
  of 
  other 
  antibacterial 
  mold 
  

   products. 
  Chemically 
  it 
  has 
  been 
  shown 
  to 
  be 
  y-keto-/3-methoxy-8- 
  

   methylene-A 
  a 
  -hexenoic 
  acid, 
  a 
  type 
  of 
  structure 
  hitherto 
  unknown 
  

   among 
  natural 
  products. 
  Penicillic 
  acid 
  is 
  rather 
  strongly 
  bacterio- 
  

   static 
  toward 
  a 
  number 
  of 
  organisms, 
  some 
  of 
  which 
  are 
  resistant 
  to 
  

   many 
  of 
  the 
  other 
  antibacterial 
  products 
  of 
  microbial 
  origin. 
  The 
  

   toxicity 
  for 
  mice 
  is 
  fairly 
  low. 
  Therapeutic 
  studies 
  have 
  not 
  been 
  

   undertaken 
  up 
  to 
  the 
  present 
  time. 
  

  

  Penicidin. 
  — 
  The 
  name 
  "penicidin" 
  has 
  been 
  given 
  to 
  an 
  antibac- 
  

   terial 
  substance 
  obtained 
  from 
  an 
  unnamed 
  species 
  of 
  Penicillium. 
  

  

  