Sources, Structures and Properties of Drug Substances

Question 1

What is a ‘lead compound’?

Answer 1

A chemical compound that shows promise for a potential treatment of a disease, and may lead to the development of a new drug

Question 2

What are the natural sources of lead compounds?

Answer 2

Plants
- Animals
- Toxins
- Microorganisms

Question 3

Give examples of drugs obtained from plants?

Answer 3

Morphine, quinine, digoxin

Question 4

What percentage of drugs commercially available have been derived from plants

Answer 4

25-30%

Question 5

How were lead compounds identified from plants in history?

Answer 5

Back in the day they were identified using a trial and error approach with written records

Question 6

How are lead compounds identified from plants now?

Answer 6

Bioprospecting:
- Can be used to produce a ‘hit’ 1 in 10,000
- can be increased to 1 in 5,000 with the implementation of traditional knowledge

Question 7

Give examples of drugs obtained from marine sources?

Answer 7

• Tetrodotoxin, taken from pufferfish and is a neurotoxin

Question 8

Give examples of drugs obtained from microorganisms?

Answer 8

Ciclosporin, benzylpenicillin,
(microorganisms are a great source of lead compounds)

Question 9

Give examples of drugs obtained from toxins?

Answer 9

Captopril and teprotide

Question 10

Give examples of drugs obtained from animals?

Answer 10

Maganin - obtained from frogs and works as an antimicrobial

Question 11

How else can lead compounds be obtained aside from natural sources?

Answer 11

They can be produced synthetically or semi-synthetically

Question 12

What is the definition of ‘semi-synthetic’?

Answer 12

Chemical manipulation of a natural product with the aim to improve activity in humans and improve the bioavailability

Question 13

Give an example of a ‘semi-synthetic’ compound?

Answer 13

6-aminopenicillic acid. This is a semi-synthetic intermediate of penicillin and can be used to produce a wide variety of penicillin analogues

Question 14

Rational Drug Design

Answer 14

Designing the most suitable structure and synthesise it with a series of analogues. Large libraries are synthesised and tested for biological activity in hopes of screening for lead compounds

Question 15

Serendipity

Answer 15

Accidentally discovering lead compounds. For example; Penicillium fungus was accidentally discovered by Alexander Fleming, which lead to the development of penicillin antibiotics

Question 16

Screening Procedures

Answer 16

Screening programmes are vital for the search of new lead compounds and can be designed to identify several types of pharmacological activity against a specific target. These involve in vitro and in vivo tests

Question 17

In vitro

Answer 17

Tests utilised in a test tube. In vitro tests utilise isolated receptors, enzymes or tissues. For example, receptors can be cloned into rapidly dividing cells to test for the affinity of a ligand to the receptor

Question 18

In vivo

Answer 18

Carried out using live animals to test biological activity conclusively. Typically more expensive than in vitro, and is more controversial. Uses animals that have been made genetically susceptive to a certain disease or condition