Antibacterial antibiotics

60 Pages·2016·0.73 MB·English

Antibacterial antibiotics
 Reference Wilson and gisvold textbook of Organic
Medical And Pharmaceutical chemistry
 Antibiotics (literally “against life”) as the biological
concept of survival of the fittest, in which one
organism destroys another to preserve itself
 The word antibiotic was derived from this root.
 An antibiotic or antibiotic substance is a substance
 produced by microorganisms, which has the capacity
of inhibiting the growth and even of destroying other
microorganisms.”
 Later proposals have sought both to expand and to
restrict the definition to include any substance
produced by a living organism that is capable of
inhibiting the growth or survival of one or more
species of microorganisms in low concentrations
 The advances made by medicinal chemists to modify
naturally occurring antibiotics and to prepare
synthetic analogs necessitated the inclusion of
semisynthetic and synthetic derivatives in the
definition.
 Therefore, a substance is classified as an antibiotic if
the following conditions are met:
 1. It is a product of metabolism (although it may be
duplicated or even have been anticipated by chemical
synthesis).
 2. It is a synthetic product produced as a structural
analog of a naturally occurring antibiotic.
 3. It antagonizes the growth or survival of one or
more species of microorganisms.
 4. It is effective in low concentrations.
CHEMICAL CLASSIFICATION
 The chemistry of antibiotics is so varied that a
chemical classification is of limited value
 Some similarities can be found, however, indicating
that some antibiotics may be the products of similar
mechanisms in different organisms and that these
structurally similar products may exert their
activities in a similar manner
 For example, several important antibiotics have in
common a macrolide structure (i.e., a large lactone
ring) e.g. erythromycin and oleandomycin
 The tetracycline family comprises a group of compounds
very closely related chemically.
 Several compounds contain closely related amino sugar
moieties, such as those found in streptomycins ,
kanamycins, neomycins, paromomycins, and gentamicins.
 The bacitracins, tyrothricin, and polymyxin are among a
large group of polypeptides that exhibit antibiotic action.
 The penicillins and cephalosporins are -lactam ring–
containing antibiotics derived from amino acids.
β-Lactam Antibiotics
Introduction
β-Lactam antibiotics are the most widely produced
and used antibacterial drugs in the world, and have
been ever since their initial clinical trials in 1941.

β-Lactams are divided into several classes based on
their structure and function; and are often named by
their origin, but all classes have a common β-Lactam
ring structure.
History
1928- Alexander Fleming discovers a mold which
inhibits the growth of staphylococcus bacteria
1940- penicillin is isolated and tested on mice by
researchers at Oxford
1941- penicillin mass produced by fermentation for use
by US soldiers in WWII
1950’s- 6-APA is discovered and semi-synthetic
penicillins are developed.
1960’s to today- novel β-lactams/ β-lactamase
inhibitors are discovered and modified from the
natural products of bacteria
Target- Cell Wall Synthesis
The bacterial cell wall is a cross linked polymer called
peptidoglycan which allows a bacteria to maintain its
shape despite the internal turgor pressure caused by
osmotic pressure differences.
If the peptidoglycan fails to crosslink the cell wall will
lose its strength which results in cell lysis.
All β-lactams disrupt the synthesis of the bacterial cell
wall by interfering with the transpeptidase which
catalyzes the cross linking process.