Lecture 13: Chemistry of Potency of Steroids

Question 1

What are adrenocorticosteroids produced by?

Answer 1

Adrenal cortex

Question 2

What are the three types of adrenocorticosteroids?

Answer 2

• Glucocorticoids
• Mineralocorticoid
• Sex hormones

Question 3

What are the glucocorticoids?

Answer 3

• Cortisol
• corticosterone

Question 4

What are the mineralocorticoids?

Answer 4

Aldosterone

Question 5

What are the functions of glucocorticoids?

Answer 5

• Regulating glucose metabolism
• Suppressing inflammation and immune response
• Maintaining cardiovascular function

Question 6

What three structures make up steroids?

Answer 6

• Cyclopentano
• Phenanthrene
• Perhydrophenanthrene

Question 7

What is the steroid backbone called?

Answer 7

Cyclopentanoperhydrophenanthrenes

Question 8

What is the steroid backbone made up of?

Answer 8

Four rings A-D with 2 methyl groups, the methyl groups have solid wedged bonds

Question 9

What is alpha and beta notation?

Answer 9

Relates to the plane within which different functional groups occupy

Question 10

Why do steroids have different enantiomers?

Answer 10

Enantiomers differ in their interactions with enzymes, proteins, receptors and other chiral molecules. These differences in interactions lead to different biological properties, different pharmacokinetics

Question 11

How many chiral centres do steroids have?

Answer 11

6

Question 12

What is the purpose of wedge and dotted bonds in steroids?

Answer 12

Dictates the plane in which the functional groups and atoms are attached to the backbone. Wedge bonds stick out, dotted stick in.

Question 13

What does beta notation mean?

Answer 13

Substituents coming out towards us - shown as a solid line

Question 14

What does alpha notation mean?

Answer 14

Substituents going back the way - shown as a broken line

Question 15

What notation does c17 uaully have?

Answer 15

Beta notation

Question 16

Why is C17 important?

Answer 16

Usually a tail that is part of a steroid molecule that is functionalized and changed in order to change their efficacy and gives the clinical effect of the steroid

Question 17

What are fusion bonds?

Answer 17

Link the two ring systems

Question 18

What conformation can fusion bonds have?

Answer 18

• Cis
• Trans

Question 19

What is a trans bond?

Answer 19

when two groups that are added across the bond and one is in alpha and one is in beta conformation

Question 20

What is a cis bond?

Answer 20

When both groups are in the same conformation

Question 21

Do natural steroids have cys type geometry?

Answer 21

No

Question 22

What do sex hormones interact with?

Answer 22

vertebrate androgen or estrogen receptors.

Question 23

What is the function of mineralocorticoids

Answer 23

Influence Salt balance and water retention

Question 24

What is the starting point for the biosynthesis of steroids?

Answer 24

Cholesterol

Question 25

What are glucocorticoids used for?

Answer 25

Treatment of rheumatoid diseases, symptomatic relief from asthma and allergic reaction and topical application for dermatologic disorders and cancer therapy (by preventing phospholipid release amongst other mechanisms)

Question 25

What are glucocorticoids used for?

Answer 25

- Treatment of rheumatoid diseases - symptomatic relief from asthma and allergic reaction - topical application for dermatologic disorders - cancer therapy (by preventing phospholipid release amongst other mechanisms)

Question 26

What are the two types of glucocorticoids?

Answer 26

- Natural - Synthetic

Question 27

GIve examples of natural steroids

Answer 27

- Hydrocortisone - Cortisone

Question 28

Name synthetic hormones

Answer 28

- Prednisone - Beclomethasone - Dexamathasone - Fluocilonone - Prednisolone - Budesonide - Betamethasone - Fluticasone

Question 29

What are the requirements for biologically active adrenocorticoids?

Answer 29

- 3 keto group - 4,5 unsaturation

Question 30

What does 4,5 unsaturation mean?

Answer 30

Means a double bond is present

Question 31

What is the name of 4,5 unsaturated bond?

Answer 31

Delta 4 steroid

Question 32

Why does the A ring require 3 keto group and 4,5 unsaturation?

Answer 32

The double bond locks the ring in shape since you cant twist a double bond

Question 33

How can glucocorticoid activity be increased?

Answer 33

- By introducing a double bond between C1 and C2 (anti-inflammatory effect enhances) - By introducing an 11 β-hydroxyl (OH) group

Question 34

How does adding double bonds increase activity of steroids?

Answer 34

Makes the ring planer so more likely to bind in the receptor pocket

Question 35

What is found at C17 of glucocorticoids?

Answer 35

alpha hydroxyl group

Question 36

What do mineralocorticoids have that give them thier activity?

Answer 36

Hydroxyl group on 21st position on ring D

Question 37

What are sex hormones usually like?

Answer 37

position c17 has a short ring- usllauy only 3/4 carbons

Question 38

Where are natural sex steroids made?

Answer 38

- by the gonads - by adrenal glands - by conversion from other sex steroids

Question 39

What is the requirement of steroids to reach target receptors in cell nuclei

Answer 39

Require significant lipophilicity

Question 40

How can clearance from the lungs be reduced?

Answer 40

By increasing lipophilicity

Question 41

Why is it often impossible to avoid off target effects and longer twerm toxicity with steroids?

Answer 41

They have strong sequence homology - amino acids sequence are almost identical, very similar active sites

Question 42

What are the routes of administration for steroids?

Answer 42

- Topical - Inhaled - Oral - Systemic

Question 43

What are inhaled steroids used for

Answer 43

use to treat the nasal mucosa, sinuses, bronchi, and lungs – such as beclomethasone and fluticasone.

Question 44

Name oral forms of steroids?

Answer 44

- Prednisone - Prednisolone

Question 45

Name systemic forms of steroids

Answer 45

- Hydrocortsone - Methylprednisolone