SL22106-Lec Natural Products and Steroids -Part 2

explain one feature of steroids

Potent molecules

What can occur with modifications

Small modifications in structure can lead to dramatically different biological effects

Lipinski’s rule of 5

Molecular weight of less than 500 Da

No more than 5 H-bond donor groups

No more than 10 H bond acceptor groups

Log P of less than 5

What is the function of cholesterol

Essential for biosynthesis

Takes place in many cells mainly in liver

HMG-CoA reductase is a key enzyme in cholesterol synthesis

strengthens lipid bilayer

Sex hormones

Progesterone

Estradiol

Testosterone

cholesterol is the precursor for all these hormones

Vitamin D3 formation

Cholesterol → Cholecalciferol/Vitamin D3

Reaction via UV light

Vitamin D activation

Cholecalciferol- from cholesterol

Calcidiol- in the liver, indicated bad liver function, may need dose reduction

Calcitriol- in the kidney, indicates bad kidney function low eGFR and need to check for meds metabolised/excreted by kidney

Regulation of plasma calcium

Absorption: in intestine

Excretion: in kidney

mobilising from bone

Immune fucntion

What are the two units

Micrograms

International units

NHS recommendation

Take 10 or 400 IU vitamin D per day

Aldosterone

Natural mineralocorticoid steroid

C7-2 x hydrogen

C17 hydroxy ketone

Where is aldosterone produced

Adrenal gland

What is aldosterone invovled in

Regulation and retention of sodium and potassium

Regulates blood volume

Spironolactone structure

beta lactone cyclic ester

Alpha thioacetate

Low MW can be taken orally

is an antagonist as it blocks aldosterone- good in patients with high aldosterone, acts as a diuretic, reduces blood pressure but maintains K+

Spironolocation uses

Heart failure

Hypertension

Potassium sparing diuretic

Testosterone

Male sex hormone

secondary sexual characteristics

motility of sperm

Testotseron Structure

Similar to estadiol but A ring not planar

Estrone

weak estrogen

not used in uk

useful for synthesis of other molecules

Esterone mechanism

Carbonyl at C17 is susceptible to attack

always goes to alpha face

Less hindering of side groups

Estradiol

Female sex hormone

Used in

Estradiol

Reduction of C3 ketone

aromatisation og A ring

loss of methyl goup at C10

A ring become planar

all these differences make it a female hormone

Ethinylestradiol

More resistant to metablism and better oral acitvity than estradiol

Cholic acid

Derived from cholesterol

Cholic acid structure

CIS AB and Trans CD system

Water soluble due to COOH

3 x OH groups

2 x Beta methyl

Cholic acid amphiphilic

One side is hydrophilic

One is hydrophobic

useful for dissolving fats via formation of micelles

Digoxin function in clinic

bradycardic and positive inotropic effects used in AF and heart failure

Heart failure symptoms

Shortness of breath

Oedema

Fatigue

Tired all the time

AF symptoms

Palpitations, chest pain, fatigue

S/E of digosxing

Toxicity

Nausea

visual disturbances: yellow halos around lights

Palpitations

to avoid: carefully titrate