Exam 2: Chapter 9

Most chemotherapy are

antibiotics

Antibiotics only work against

bacteria

• NOT viruses

Thomas & Bretheim made

atoxyl

Atoxyl is used to treat

african sleeping sickness

Why isnt atoxyl used anymore?

contains arsenic that causes blindness

Paul Ehrlich & Sahachiro Hata created

salvarsan

Salvarsan is used to treat

trepomenta pallidum which is the cause of syphillus

Why isnt Salvarsan used anymore?

its an arsenic compound

• dyes & selective toxicity

Gerhard Domagk, Jacques, and Therese Trefouel discovered

sulfonamides and sulfa drugs

Salvarsan and Prontosil are the

first two antibiotics

The three categories of antibiotics

true, synthetic, and semi-synthetic

True antibiotics

made by living organisms

Synthetic antibiotics

chemical compounds found in organic labs

Example of synthetic antibiotics

salvarson and prontosil

Example of true antibiotics

penicillin

Semi-synthetic antibiotics are

modified compounds of a true antibiotic

Example of semi-synthetic antibiotics

penicillin being modified to ampicillan

Chemotherapy

the use of chemical compounds to deal with a disease

The first true antibiotic was

penicillin

What is penicillin made from?

the fungus penicillium

Ernest Duchesne was the first to

notice a fungus and bacteria near it were not growing (zone of inhibition)

• eventually got lost in his notes

Alexander Fleming

noticed the zone of inhibition but didnt know what to do with the information

Florey, Chain, & Heatley

get credit for penicillin discovery

• found that the pencillin molecule was being made by a fungus

Streptomycin was identified by

selman waksman

• first to trat TB successfully

By 1953, what was discovered?

chloramphenicol, terramycin, neomycin, and teyracycline

Actinomycetes are

a group of organisms

Streptomyces is a

bacteria, NOT a fungus

• makes the most true antibiotics

Streptomyces grows through

filamentous reproduction

Abaucin is a

narrow spectrum antibiotics that works against Baumannii

• doesnt harm many other bacteria

In 2022, AI work yielded

potential drugs against Acinetobacter baumannii and many other drug-resistant bacteria

Selective toxicity

wants to harm the bad cells and leave the good cells alone

• “magic bullet”

Therapeutic index

safe zone for a drug

The larger the therapeutic index,

the better the drug (the safer it is)

Antifungal drugs have

a very small therapeutic index

Narrow spectrum

only inhibits a few bacteria/kills a few bacteria

Example of narrow spectrum

vancomycin has a small window of killing/inhibiting gram-positives

Broad spectrum

inhibits/kills multiple bacteria

Example of broad spectrum

tetracycline inhibits/kills gram-negative, gram-positive, and atypical bacteria

Static means

minimal inhibitory concentration (MIC)

Static

compound will inhibit the microbe from replicating/growing

Cidal means

minimal lethal concentration (MLC)

Cidal

kills; how much of the drug do we need to use to kill the microbe

Antimicrobial Drugs

• inhibitors of cell wall synthesis

• protein synthesis inhibitors

• metabolic antagonists

• nucleic acid synthesis inhibition

Penicillin

inhibits the making of the cell way because it inhibits the process of transpeptidation

Transpeptidation

inhibits enzyme transpeptidase

B-lactamase is

broad

Penicillinase is

specific

Semisynthetic penicillins are

broad-spectrum

Pencillin V and G are

true antibiotics against only gram positive bacteria

B-lactam will bind to

the transpeptidase

• inhibits process of transpeptidation

Penicillin V and G come from

the fungus pencillum

B-lactamase are

enzymes made by bacteria that breaks the B-lactam ring

• if this ring breaks, penicillin doesnt work

A bacteria can become resistant to penicillin by

making B-lactamase which then breaks the B-lactam ring, where there is no more function

True antibiotics are generally

narrow spectrum

Penicillin has a

5 membered ring associated with the B-lactam ring

Does penicillin have sulfur?

no

Does penicillin have a double bond?

no

Cephalosporins come from

the fungus Acremonium

Cephalosporin is a

broad spectrum antibiotics

Cephalosporin can be used by

most patients allergic to penicillin

Cephalosporin has a

6 membered ring

Cephalosporin is an antibiotic that contains what?

B-lactam

Does Cephalosporin inhibit the cell wall?

yes

Penem is modified

pencillin and cephalosporin hybrid drugs

Cabapenem is a

semi-synthetic antibiotic

Carbapenem has a

5 membered ring

Does carbapenem have sulfur?

no

Does Carbapenem have a double bond?

yes

Does Carbapenem inhibit cell wall synthesis?

yes

Carbapenem is more

broad spectrum than penicillin

Vancomycin is a

true antibiotic made by bacteria

Vancomycin is a glycopeptide produced by what bacteria?

streptomyces orientalis

Vancomycin

inhibits cell wall synthesis

What bacteria does Vancomycin work on?

gram positives only

• ex: staphylococcus, clostridium, bacillus, streptococcus, enterococcus

Vancomycin is considered the

“drug of last resort”

Vancomycin resistant enterococcus (VRE)

spread easily through not washing hands and eating contaminated food

Streptomyces is

a bacteria that has many members/many species that release compounds to kill their neighbors

Streptomyces genus’s

make the majority of true antibiotics

Is Vancomycin broad spectrum or narrow spectrum?

broad spectrum

Protein Synthesis Inhibitors

many antibiotics bind specifically to the bacterial ribosome

• rRNA or protein

70S is found in

bacteria, archaea, and mitochondria

Translocation

movement of tRNAs from A to P from P to E

Large subunit (50S)

has a site that allows for the addition of the amino acid

• where actual peptide bond forms

Small subunit (30S)

where mRNA is located

When the large subunit and small subunit are put together,

it becomes 70S and is found in bacteria, archaea, and mitochondria

The size of ribosomes in eukaryotes is

80S

• 60S and 40S

Mitochondria are

transcribed and translated into subunits that make the electron transport chain (ETC), which allows for the making of ATP

If you inhibit the mitochondria ribosome,

there is no translation of polypeptides and no ETC

If there is no ETC, mitochondria

doesnt work properly and the cell has no energy

• wont be able to survive

Aminoglycosides are

bactericidal, broad-spectrum drugs

What subunit does Aminoglycosides bind to?

the 30S subunit

Aminoglycolysis members

• streptomycin

• kanamycin

• neomycin

Aminoglycosides goal

is to inhibit the making of polypeptides

Streptomycin, kanamycin, neomycin are apart of what genus?

streptomyces

Gentamicin is a

true antibiotic

What bacteria is Gentamicin made by?

Micromonospora purpurea

Tetracycline has what structure?

a four ringed structure

Which subunit does tetracycline bind to?

the small subunit (30S)

Oxytetracycline and chlortetracycline are

true antibiotics

What is the outcome of tetracycline?

black teeth (cannot be reversed) and liver toxicity

• not prescribed to pregnant women