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PHA3042
2015
Eva.Patak@monash.edu
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Monash University
sources of drugs
source (noun)
a place, person or thing from which
something originates or can be obtained
Oxford dictionary
sources of drugs
natural
synthesised in lab
sources of drugs
despite central role that drugs play in
healthcare most people dont know where
drugs come from
synthetically produced (1st world)
natural products (3rd world)
secondary metabolites
possess no obvious primary metabolic function
originally believed to be waste products
now thought to contribute to the producers
fitness i.e. enhance chances of survival
defence against predators or pathogens
can be used both defensively (e.g. plants) or
offensively (e.g. snakes, spiders)
vast array of metabolites (e.g. in plants
>120,000 known structures) which exhibit a
diverse range of pharmacological activity
bioactive molecules
alkaloids
basic nitrogen-containing compound
white crystalline substance
bitter
e.g. morphine, atropine, quinine
glycosides
contains sugar moiety (glycone) + non-sugar
moiety (aglycone)
classified according to chemical nature of
aglycone group
e.g. cardiac glycosides, flavanol glycosides
Where to look?
Healer living in Belize, Central America, collecting the leaves and flowers of the
plant Cornutia pyramidata to include in a mixture used for skin rashes.
animal-based drugs
animals important source of drugs
examples include:
hormones
insulin derived from pancreas of pigs & cows
oestrogen from urine of pregnant mares
heparin
anticoagulant derived from bovine lungs & pig
intestine
animal-based drugs
venoms and toxins of particular interest
found in many vertebrate/invertebrate species
poison dart frogs used for centuries by some
indigenous South American cultures for hunting
venoms highly complex mixtures
contain proteins, polypeptides, enzymes, free
acids
snake venoms
venom often classified as either neurotoxic or
hemotoxic
neurotoxic
produce paralysis (mostly) mediated at neuromuscular
junction
prey / victim dies of respiratory failure
hemotoxic
toxins affect coagulation
increase bleeding
discovery of captopril
John Vane a consultant at Squibb interested in
hypertension and believed that angiotensin converting
enzyme (ACE) important in regulating blood pressure
Brazillian post-doc Sergio Ferreria joined Vanes lab and
brought with him extract of Brazilian viper venom
bradykinin potentiating factor
also found to be potent ACE inhibitor
discovery of captopril
initial clinical trials showed decrease in BP when
administered intravenously
peptide not absorbed when taken orally
Squibb then tackled issue of making an oral drug
$1 million/kg to synthesise
captopril went on to become Squibbs first billion dollar
drug
released in Australia in 1982
synthetically synthesised
microorganism-based drugs
prokaryotes make up more than 50% of the
earths biomass
estimated number is 5 x 1030
Important source of many drugs
fungi antibiotics (penicillin), some statins,
ergot derivatives
bacteria antibiotics particularly of genus
Streptomyces e.g. tetracycline, chloramphenicol
still a potential for future drug development
microorganism-based drugs
defense mechanisms
many sessile invertebrates:
feed by filtering seawater
seawater contains high levels of bacteria
produce anti-bacterial compounds?
summary
untapped pharmacological potential
discovery
access to areas of high biodiversity
United Nations Convention on Biological
Diversity
loss of diversity
cost
natural source vs chemical synthesis
learning outcomes
describe how natural compounds have led to
the development of therapeutics
discuss the potential natural sources still hold
for the development of new therapeutic
entities
understand the issues involved in using natural
sources to develop new therapeutics