Lecture 13: Chemistry of Potency of Steroids Flashcards
What are adrenocorticosteroids produced by?
Adrenal cortex
What are the three types of adrenocorticosteroids?
- Glucocorticoids
- Mineralocorticoid
- Sex hormones
What are the glucocorticoids?
- Cortisol
- corticosterone
What are the mineralocorticoids?
Aldosterone
What are the functions of glucocorticoids?
- Regulating glucose metabolism
- Suppressing inflammation and immune response
- Maintaining cardiovascular function
What three structures make up steroids?
- Cyclopentano
- Phenanthrene
- Perhydrophenanthrene
What is the steroid backbone called?
Cyclopentanoperhydrophenanthrenes
What is the steroid backbone made up of?
Four rings A-D with 2 methyl groups, the methyl groups have solid wedged bonds
What is alpha and beta notation?
Relates to the plane within which different functional groups occupy
Why do steroids have different enantiomers?
Enantiomers differ in their interactions with enzymes, proteins, receptors and other chiral molecules. These differences in interactions lead to different biological properties, different pharmacokinetics
How many chiral centres do steroids have?
6
What is the purpose of wedge and dotted bonds in steroids?
Dictates the plane in which the functional groups and atoms are attached to the backbone. Wedge bonds stick out, dotted stick in.
What does beta notation mean?
Substituents coming out towards us - shown as a solid line
What does alpha notation mean?
Substituents going back the way - shown as a broken line
What notation does c17 uaully have?
Beta notation
Why is C17 important?
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
What are fusion bonds?
Link the two ring systems
What conformation can fusion bonds have?
- Cis
- Trans
What is a trans bond?
when two groups that are added across the bond and one is in alpha and one is in beta conformation
What is a cis bond?
When both groups are in the same conformation
Do natural steroids have cys type geometry?
No
What do sex hormones interact with?
vertebrate androgen or estrogen receptors.
What is the function of mineralocorticoids
Influence Salt balance and water retention
What is the starting point for the biosynthesis of steroids?
Cholesterol
What are glucocorticoids used for?
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)
What are glucocorticoids used for?
- 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)
What are the two types of glucocorticoids?
- Natural
- Synthetic
GIve examples of natural steroids
- Hydrocortisone
- Cortisone
Name synthetic hormones
- Prednisone
- Beclomethasone
- Dexamathasone
- Fluocilonone
- Prednisolone
- Budesonide
- Betamethasone
- Fluticasone
What are the requirements for biologically active adrenocorticoids?
- 3 keto group
- 4,5 unsaturation
What does 4,5 unsaturation mean?
Means a double bond is present
What is the name of 4,5 unsaturated bond?
Delta 4 steroid
Why does the A ring require 3 keto group and 4,5 unsaturation?
The double bond locks the ring in shape since you cant twist a double bond
How can glucocorticoid activity be increased?
- By introducing a double bond between C1 and C2 (anti-inflammatory effect enhances)
- By introducing an 11 β-hydroxyl (OH) group
How does adding double bonds increase activity of steroids?
Makes the ring planer so more likely to bind in the receptor pocket
What is found at C17 of glucocorticoids?
alpha hydroxyl group
What do mineralocorticoids have that give them thier activity?
Hydroxyl group on 21st position on ring D
What are sex hormones usually like?
position c17 has a short ring- usllauy only 3/4 carbons
Where are natural sex steroids made?
- by the gonads
- by adrenal glands
- by conversion from other sex steroids
What is the requirement of steroids to reach target receptors in cell nuclei
Require significant lipophilicity
How can clearance from the lungs be reduced?
By increasing lipophilicity
Why is it often impossible to avoid off target effects and longer twerm toxicity with steroids?
They have strong sequence homology - amino acids sequence are almost identical, very similar active sites
What are the routes of administration for steroids?
- Topical
- Inhaled
- Oral
- Systemic
What are inhaled steroids used for
use to treat the nasal mucosa, sinuses, bronchi, and lungs – such as beclomethasone and fluticasone.
Name oral forms of steroids?
- Prednisone
- Prednisolone
Name systemic forms of steroids
- Hydrocortsone
- Methylprednisolone
