D.2 (PART 2): PENICILLIN
INTRO: https://www.youtube.com/watch?v=CQG5B27euPo (PENICILLIN – PERIODIC TABLE OF VIDEOS)
UNDERSTANDINGS
- Penicillins are _______________ produced by ____________.
- A _________-___________ ring is a part of the core structure of penicillins.
- Some antibiotics work by preventing cross-linking of the bacterial cell ___________.
- Modifying the __________-chain results in penicillins that are more resistant to the penicillinase ____________.
APPLICATION AND SKILLS
- Discussion of the effects of chemically modifying the side-chain of penicillins
- Discussion of the importance of patient compliance and the effects of the over-prescription of penicillin.
- Explanation of the importance of the beta-lactam ring on the action of penicillin.
INTRO:
Q. What are antibacterials called in many countries? ____________________
Q. What do antibacterials do?
A. Antibacterials are drugs that ________________ the growth of, or kill, ___________________ that cause
_______________________ diseases; they are used to control predominantly ___________________ infections (*they are effective
in combating a few ________________).
Q. Antibacterials are referred to as being selective drugs. What does this mean?
A. Antibacterials act against infecting _______________ much more than they act against _________ cells.
1. DISCOVERY AND GENERAL STRUCTURE
YEAR
1890s
EVENT / DISCOVERY
-scientists discovered that certain ______________ killed bacteria
-experiments on mice  bacterial infection prevented when exposed to these fungi; initial successes largely
_______________
1928
-discovery of penicillin
-Alexander Fleming, a bacteriologist working in England, made similar observations to those made some 30 years
earlier while working with an infectious _____________ called staphylococcus aureus. He found, rather
serendipitously, that a ___________ (penicillium notatum) growing in a petri dish containing this bacterium
_______________ the growth of the bacterium. He called the compound in the mold that was responsible for this
inhibition ______________________.
- Fleming gave up the project after being unable to ________________ and _____________ the penicillin.
1940
1941
- more mice experiments – mice infected with deadly bacteria given penicillin – mice __________
- Penicillin first used on a _________________ in an attempt to combat serious __________poisoning – effect was
immediately ___________________.
- penicillin mold produced on a _______________ scale in the _____________ (labouriously grown in large tanks
containing corn-steep liquor)
1943
- penicillin available ______________________
1945
- supply of penicillin large enough to meet the demand (i.e. everyone suffering from an infectious disease / thousands of
lives saved during ______________)
- Fleming, Florey and Chain receive Nobel Prize for ________________
1950s
- _________________ of penicillin determined
- enabled synthesis of different types of penicillin and other antibiotics in the _______ without recourse to moulds
e.g. PENICILLIN G
- the ____________ penicillin
- broken down by stomach __________ so had to be __________
- _____________ able to deactivate by synthesizing an enzyme (penicillinase)
or
*Identify on the above diagrams:
(i) basic structure of all penicillins
(ii) the “R” group
(iii) the beta-lactam ring
SIDE-CHAIN MODIFICATIONS
-alters properties of the penicillin
e.g. PENICILLIN V
AMOXICILLIN
- acid resistant
- basic penicillin structure maintained; side-chains modified
2. MODE OF ACTION
-THE BETA LACTAM RING
-All penicillins contain a ____________-membered beta-lactam ring.
-The high reactivity of the ____________ group within this ring structure is a result of
ring _____________. The ring opens so that the penicillin becomes ________________
bonded to the enzyme that synthesizes bacterial cell _________, thus blocking its action.
Thus, penicillins work by preventing bacteria from making normal cell ______.
Ultimately, the cell swells, and the _____________ pressure causes the wall to
disintegrate and the bacterium dies.
- Identify the four membered beta-lactam ring on the adjacent penicillin. Label each
member, 1 to 4, starting in the upper left and moving clockwise.
Carbon (#1) = ______ hybridized ; normal bond angle = ________
Carbon (#2) = ______ hybridized ; normal bond angle = ________
Nitrogen(#3) =______hybridized ; normal bond angle =_________
Carbon(#4) = _______hybridized ; normal bond angle = _________
- These normal bond angles are unable to be obtained. This makes the ______________ group in the ring highly reactive as the ring
can readily break due to _____________angles. When the ring opens these parts of the penicillin become _____________ bonded to
the enzyme that synthesizes bacterial cell walls, thus blocking its action.
-THE DETAILS: The beta-lactam structure is very similar to the combined structure of two amino acids - _____________ +
__________. These amino acids are used to synthesize bacteria cell walls. The __________ that synthesizes these cell walls “thinks”
it is bonding to these amino acids when, in fact, it is bonding to the structurally similar penicillin.
3. RESISTANCE TO PENICILLINS
-Penicillin has been often overprescribed in the past…especially when it became readily available in the 1950s.
-Resistant penicillin possess the enzyme penicillinase.
*DISADVANTAGES OF OVER-PRESCRIBING PENICILLINS
1.
REACTIONS
- about _______% of the population is allergic to penicillin
- __________________ use can sometimes lead to allergic reaction
2. DESTROYING OF
BACTERIA
- repeated use can eliminate _____________ and ___________ bacteria in the ___________________tract
3. RESISTANCE PROBLEMS
(a)
Resistance  some bacteria develop resistance to a particular antibiotic and pass on this immunity to
succeeding generations (e.g. malaria, typhoid, gonorrhea, TB all have strains that are resistant to many antibiotics)
(b) Resistance due to
 random, favourable alterations to a bacteria’s ________ that result in resistance
(c) Use of Penicillin in
Feedstock  ________________ and ___________ are given the _______________
antibiotics that humans are in order to increase ________________. Therefore, more bacteria are able to develop ________________
within animal feedstock as a result of this increased exposure to the antibiotic.
**As a result of all these potential resistance problems, antibiotics are in constant need of ____________ and should only be
prescribed as a _________ resort.
*YOUTUBE: GENERAL INTEREST VIDS:
1. ‘What Causes Antibiotic Resistance?’ (Kevin Wu)
2. Tuberculosis Documentary: ‘The Deadliest Killer in Human History –The Forgotten Plague’
3. ‘The Black Death National Geographic Documentary”