Ref.Book 428PHC:
“Foyes Principles of Medicinal Chemistry”
Dr. fatmah alomary
Falomary@ksu.edu.sa
Chemotherapeutic Agents
Chemotherapeutic Agents

 Chemotherapy is a general term referring to the use of a drug
to kill or weaken invading cells or organisms without harming
the patient. Such invading organisms may be bacteria,
protozoa, worms, and viruses or tumors. Hence, if we wish to
be more precise in designating a chemotherapeutic agent, we
may
speak
of
antibacterial,
antiprotozoal,
anthelmintic,
antiviral, or antitumor drugs.
 All clinically useful chemotherapeutic agents are more toxic
to the organism than to the patient and may be used internally
to treat systemic infections.
Antibacterial Agents

-The fight against bacterial infection is one of the great success stories of
medicinal chemistry.
Antibiotic agent is an antibacterial agent derived from a natural source.
Antibacterial agent
is a synthetic or naturally occurring agent which
can kill or inhibit the growth of bacterial cells.
 The bacterial cell
 The success of antibacterial agents owes much to the fact
that they can act selectively against bacterial cells rather
than animal cells. This is largely due to the fact that bacterial
cells and animal cells differ both in their structure and in the
biosynthetic pathways which proceed inside them.
 The differences between the bacterial cell and
the animal cell:
 1-The bacterial cell does not have a defined nucleus, whereas
the animal cell does.
 2-Animal
cells
contain
a
variety
of
structures
called
organelles (e.g. mitochondria, etc.), whereas the bacterial cell
is relatively simple.
 3-The biochemistry of a bacterial cell differs significantly from
that of an animal cell. For example, bacteria may have to
synthesize essential vitamins which animal cells can acquire
intact from food. The bacterial cells must have the enzymes
to catalyse these reactions. Animal cells do not, since the
reactions are not required
 4-The bacterial cell has a cell wall, as well as a cell
membrane, whereas the animal cell has only a cell membrane.
 Mechanism of antibacterial actions:
 There are five main mechanisms by which antibacterial
agents act.
 1-Inhibition of bacterial cell wall synthesis: leads to bacterial
cell lysis (bursting) and death. Agents operating in this way
include penicillins and cephalosporins and vancomycin
 2- Inhibition of cell metabolism: Antibacterial agents which
inhibit cell metabolism are called antimetabolites. These
compounds inhibit the metabolism of a microorganism, but
not the metabolism of the host. They do this by inhibiting an
enzyme-catalysed reaction which is present in the bacterial
cell, but not in animal cells. The best known examples of
antibacterial agents acting in this way are the sulfonamides
 3- Interactions with the plasma membrane: Some antibacterial
agents interact with the plasma membrane of bacterial cells
to affect membrane permeability. This has fatal results for the
cell. Polymyxins and tyrothricin operate in this way.
 4- Disruption of protein synthesis: means that essential
enzymes required for the cell's survival can no longer be
made. Agents which disrupt protein synthesis include the
rifamycins,
aminoglycosides,
tetracyclines,
and
chloramphenicol.
 5- Inhibition of nucleic acid transcription and replication:
Inhibition of nucleic acid function prevents cell division
 and/or the synthesis of essential enzymes. Agents acting in
this way include nalidixic acid and proflavin.
Antimicrobial agents
 Antimicrobial agents fall into two general classes:
 I-Antibiotics: Are chemicals that are produced by microorganisms having the capacity to inhibit, at high dilutions, the
growth of or to kill, bacteria and other microorganisms, such
as
penicillin,
cephalosporin,
tetracycline
and
chloramphenicol.
 II-Synthetic chemothernpcutic Agents: such as sulfonamides,
isonicotinic acid hydrazide and the quinolones.
 Antimicrobial
according
to
bacteriostatic
agents:
their
are
effect
(inhibitory) or
also
on
the
frequently
microbe
bactericidal
classified
as
either
(lethal) agents.
Bacterostatic: are drugs inhibit the growth and multiplication
of bacteria, but do not directly kill them (e.g. sulphonamides,
chloramphenicol.
 Bactericidal : are drugs irreversibly damage and kill bacteria,
usually by attacking the cell wall or plasma
cephalosporins, aminoglycosidcs, rifumpicin
(e.g. penicillin,