Natural Product Chemistry Part 1

Question 1

Outline the 10 steps of drug discovery

Answer 1

1. Biomass( plant , microbes ,marines)
2. Extraction
   3.screening ( LTS/HTS)
3. Bioassay -guided isolation of actives
4. Cross screening
   6.Structure elucidation
5. Large scale isolation
6. Chemical modification
7. In vivo studies
8. Clinical trails
   =DRUG

Question 2

Describe biomass, extraction and screening process

Answer 2

First biomass (plant ) is collected , dried end extracted into a suitable solvent
Screened to assess biological activity either through low/high throughput screening

Question 3

Bioassay-guided isolation of actives , cross screening, structure elucidation, large scale isolation

Answer 3

Active extracts are fractioned using chromatography technique , activity assesss . Natural product isolated will be lead compound and will be assessed for activity. Structure elucidation to determine what chemical class it belongs to , 3D structure and wether it has been previously reported to have activity . Large scale isolation occurs

Question 4

Chemical modification, in vivo studies , clinical trails , drug

Answer 4

Chemical modification to enhance activity . In vivo studies to assess toxicity and efficacy and then drug enters clinical trails

Question 5

Classses of natural products (5)

Answer 5

Polyketides
Terpenes
Alkaloids
Glycosides
Shikimic acid derived natural plants

Question 6

Examples of polyketides and define

Answer 6

Polyketides are acetate derived metabolites occurring throughout all organisms.
Fatty acids and Glycerides
Tetracycline
Grideofulvin
Erythomycin a
Statins

Question 7

Biosynthesis of polyketides

Answer 7

Condensation of malonyl-CoA with acetyl-CoA to form aceto acetyl CoA known by claisen reaction
The formed acetoacetyl CoA reacts with malonyl CoA by same reaction to form long chain fatty acids

Question 8

Used of fatty acids and examples

Answer 8

Formulations agents and vehicles in pharmacy as cosmetics and soaps
Examples
oleic acid (major component of olive oil)
Alpha-linolenic (major constituent of linseed oil)

Question 9

Tetracycline
Use , examples and what the structure contains

Answer 9

Activity against gram positive and negatives (broad spectrum)
Ex-doxycycline
Structures- tertiary amine, amide group, chelating group , alpha, beta unsaturated ketone
Comes from mutants of streptomyces aureofaciens

Question 10

Griseofulvin, derived from? And uses?

Answer 10

Derived -fungus penicillium griseofulvin
Systemic treatment of fungal infections of hair, skin , nails and feet belonging to genera microsporum and others

Question 11

Erythromycin A , derived, uses?

Answer 11

Use treat respiratory conditions patients allergic to penicillins
Derived from actinomycete which is a filamentous bacterium

Question 12

Statins , uses , example

Answer 12

Lower TC
Examples : lovastatin

Question 13

Describe shikimic derived acid and examples of class under the compound (5)

Answer 13

Simple acid precursor of natural products and aromatic amino acids including tyrosine .
Classes
Lignans
Tannins
Coumarins
Flavonoids
Phenylpropenes

Question 14

1.Cinnamaldehyde biosynthesis from phenylalanine

Answer 14

Biosynthesized into cinnamic acid through oxidation phenylalanine in presence of enzyme phenylalanine ammonia lyase to form cinnamaldehyde which is used to make cinnamon oil (used as spice and flavoring)it undergoes reduction

Question 15

Lignans synthesis and uses

Answer 15

Coupling 2 of phenylpropene unit
Podophyllotoxin - highly toxic not used clinically

Question 16

Coumarins synthesis and examples with uses

Answer 16

Formed from phenylalanine then undergoes deamination and hydroxylated to trans-hydroxycinnamic acid and converted to cis-hydroxycinnamic acid , lactonization forms coumarin
Examples -psoralens-used to prepare sunscreen and promote skin pigmentation

Question 17

Flavonoids uses

Answer 17

Contribute to color and uses have antioxidant properties

Question 18

Tannins and uses

Answer 18

Water soluble polyphenolic compounds
Tannic acid Used as topical preparation for cold sores