﻿CHEMOTHERAPEUTIC 
  AGENTS 
  — 
  WEINTRAUB 
  565 
  

  

  So 
  far 
  such 
  studies 
  have 
  been 
  made 
  in 
  only 
  one 
  or 
  two 
  cases 
  but 
  

   these 
  have 
  proved 
  very 
  fruitful. 
  It 
  has 
  been 
  mentioned 
  that 
  the 
  

   two 
  mold 
  products, 
  fumigatin 
  and 
  spinulosin, 
  are 
  structurally 
  very 
  

   similar, 
  differing 
  only 
  in 
  the 
  possession 
  of 
  an 
  additional 
  hydroxyl 
  

   group 
  by 
  the 
  latter. 
  Spinulosin 
  was 
  found 
  to 
  have 
  only 
  about 
  one- 
  

   tenth 
  the 
  antibacterial 
  potency 
  of 
  fumigatin. 
  This 
  unexpected 
  dis- 
  

   covery 
  that 
  the 
  activity 
  was 
  markedly 
  decreased 
  by 
  the 
  introduction 
  

   of 
  a 
  hydroxyl 
  group 
  led 
  to 
  a 
  study 
  of 
  a 
  considerable 
  number 
  of 
  sub- 
  

   stituted 
  toluquinones 
  and 
  benzoquinones, 
  from 
  which 
  several 
  impor- 
  

   tant 
  generalizations 
  concerning 
  the 
  effect 
  of 
  structure 
  on 
  activity 
  

   could 
  be 
  drawn. 
  As 
  a 
  valuable 
  byproduct 
  of 
  the 
  investigation, 
  it 
  

   was 
  found 
  that 
  several 
  of 
  the 
  compounds 
  tested 
  were 
  more 
  potent 
  

   than 
  fumigatin 
  itself. 
  

  

  A 
  variety 
  of 
  effects 
  is 
  produced 
  by 
  the 
  different 
  antibacterial 
  agents 
  

   of 
  microbial 
  origin. 
  At 
  the 
  one 
  extreme 
  are 
  those 
  like 
  actinomycetin 
  

   and 
  lysozyme 
  which 
  cause 
  the 
  disintegration 
  of 
  the 
  bacterial 
  cells. 
  

   Others, 
  such 
  as 
  gramicidin, 
  may 
  also 
  produce 
  dissolution 
  but 
  pre- 
  

   sumably 
  only 
  through 
  the 
  self-digestion 
  brought 
  about 
  by 
  the 
  enzymes 
  

   of 
  the 
  killed 
  cells. 
  Killing 
  without 
  lysis 
  is 
  brought 
  about 
  by 
  a 
  num- 
  

   ber 
  of 
  substances 
  : 
  pyocyanine, 
  clavacin, 
  fumigacin, 
  gliotoxin, 
  notatin, 
  

   etc. 
  The 
  least 
  drastic 
  action 
  is 
  that 
  of 
  such 
  agents 
  as 
  actinomycin 
  

   which 
  are 
  primarily 
  bacteriostatic, 
  preventing 
  growth 
  or 
  reproduction 
  

   without 
  killing 
  the 
  cells. 
  

  

  As 
  might 
  be 
  expected, 
  an 
  even 
  greater 
  diversity 
  appears 
  to 
  exist 
  

   among 
  the 
  mechanisms 
  by 
  which 
  the 
  antibacterial 
  effects 
  are 
  brought 
  

   about. 
  In 
  very 
  few 
  cases 
  has 
  much 
  insight 
  been 
  gained 
  into 
  these 
  

   mechanisms, 
  but 
  progress 
  is 
  being 
  made 
  rapidly. 
  

  

  Ehrlich 
  and 
  other 
  early 
  workers 
  in 
  the 
  field 
  of 
  chemotherapy 
  pro- 
  

   ceeded 
  largely 
  on 
  the 
  assumption 
  that 
  the 
  most 
  effective 
  agents 
  would 
  

   be 
  those 
  which 
  produced 
  the 
  maximum 
  killing 
  of 
  the 
  pathogens 
  

   without 
  greatly 
  damaging 
  the 
  cells 
  of 
  the 
  host, 
  a 
  sort 
  of 
  selective 
  

   sledge-hammer 
  action. 
  In 
  later 
  years 
  it 
  has 
  become 
  apparent, 
  how- 
  

   ever, 
  that 
  actual 
  killing 
  of 
  the 
  parasite 
  by 
  the 
  chemical 
  agent 
  itself 
  

   may 
  not 
  be 
  at 
  all 
  necessary. 
  The 
  natural 
  defense 
  mechanisms 
  of 
  

   the 
  body 
  in 
  many 
  cases 
  are 
  able 
  to 
  cope 
  with 
  a 
  limited 
  number 
  of 
  

   invaders 
  and 
  can 
  effect 
  their 
  elimination 
  if 
  the 
  bacterial 
  multiplica- 
  

   tion 
  can 
  be 
  prevented. 
  Prevention 
  of 
  reproduction 
  can 
  be 
  achieved 
  

   through 
  interference 
  with 
  some 
  metabolic 
  process 
  of 
  the 
  micro-organ- 
  

   ism 
  and, 
  since 
  the 
  biochemical 
  processes 
  of 
  the 
  bacterial 
  cell 
  differ 
  

   in 
  numerous 
  respects 
  from 
  those 
  of 
  higher 
  animals, 
  there 
  exists 
  the 
  

   possibility 
  that 
  there 
  may 
  be 
  found 
  subtle 
  methods 
  of 
  interference 
  

   which 
  will 
  be 
  relatively 
  innocuous 
  to 
  the 
  host. 
  

  

  An 
  outstanding 
  example 
  of 
  such 
  a 
  state 
  of 
  affairs 
  is 
  furnished 
  by 
  

   the 
  action 
  of 
  sulfanilamide. 
  One 
  of 
  the 
  essential 
  growth 
  factors, 
  

  

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