MEDCHEM

Which of the following statements is true in relation to phase II metabolism?

Phase II metabolism involves the oxidation of drugs by cytochrome P450 enzymes. 

Phase II metabolism usually leads to a drug molecule with a higher molecule weight. 

Phase II metabolism typically results in the formation of more hydrophobic drug molecules. 

Phase II metabolism involves the hydrolysis of esters using esterases. 

Phase II metabolism usually leads to a more active drug molecule.

Phase II metabolism usually leads to a drug molecule with a higher molecule weight. 

Phase I Metabolism Metabolism by hydrolysis: esterases and peptidases can potentially

hydrolyse any ester or amide

Phase I Metabolism Metabolism by hydrolysis:

Etomidate is a

short-acting intravenous anesthetic,

Phase I Metabolism Metabolism by hydrolysis:

Etomidate is inactivated in the

blood plasma

Phase I Metabolism Metabolism by hydrolysis:

Etomidate is inactivated in the blood plasma by the actions of

esterases.

Phase I Metabolism Metabolism by hydrolysis:

The enzyme hydrolyses the ester to the corresponding

carboxylic acid

Phase I metabolism is carried out by various enzymes -

cytochrome P450s (CYPs), monoamine oxidase, \n flavin monooxygenase, xanthine oxidase, esterases/peptidases (hydrolysis)

Phase II Metabolism conjugation: \n Glucuronidation/sulphation occur typically at ? groups

phenol, alcohol and carboxylic acid

Phase I metabolism, products are often more

reactive

Phase II Metabolism conjugation:

The products of conjugation are typically higher in ? and less ? than the parent compounds

MW, reactive

Phase II Metabolism conjugation:

The process is ? mediated (transferases)

enzyme

Phase II Metabolism conjugation:

The ? group may have been already present in the drug, or added during phase I metabolism

OH

Phase I Metabolism Oxidative metabolism Reactions mediated by

CYPs

Phase I Metabolism Oxidative metabolism PLACES:

At carbon where a radical can be stabilised

Aromatic & heteromatic rings, alkenes, sulphur

Electron rich groups are most prone to oxidation

Phase I EVENTS –

oxidation, reduction, hydrolysis

Phase II EVENTS –

conjugation

In relation to structure activity relationships for a particular drug molecule, changing a secondary amide to a secondary amine is most likely to reveal that:

the carbonyl is not essential for activity 

ionic interactions are essential for activity 

the nitrogen is essential for activity 

electrostatic interactions are not important for binding 

the nitrogen is not essential for activity 

van der Waals interactions are not playing a significant part in drug binding 

the carbonyl is not essential for activity 

DRUGS BIND TO TARGET van der Waals Interactions

KNOWN AS

London dispersion forces

DRUGS BIND TO TARGET van der Waals Interactions \n These are ? interactions

short range, relatively weak

DRUGS BIND TO TARGET van der Waals Interactions

can be extremely important for ?

binding

DRUGS BIND TO TARGET van der Waals Interactions

Require ? between drug and target

close contact

An important feature of enzymes is their high substrate specificity and this is due to a series of non-covalent enzyme-substrate interactions:

• Electrostatic \n • Hydrogen bonding \n • Non-polar (Van der Waals) interactions \n • Hydrophobic

electrostatic/ionic bonds:

? intermolecular interaction

strongest

electrostatic/ionic bonds:

take place between

groups of opposite charge

electrostatic/ionic bonds:

stronger interactions occur in

hydrophobic environments

electrostatic/ionic bonds:

very important as drug

enters binding site

Amines Prevents nitrogen acting as a ?, due to resonance

HBA

Amines Prevents nitrogen acting as a HBA, due to ?

resonance

Carboxylic acids

May exist as carboxylate ion, where there is the possibility of

ionic interactions or very strong H-bond acceptor

The carbonyl oxygen has greater electron density and is less hindered than the alkoxy oxygen, so will typically be a better

HBA

The relevance of the carbonyl group could be tested by

making the equivalent ether analogue

The carbonyl oxygen has greater ? and is less ? than the alkoxy oxygen, so will typically be a better HBA

electron density, hindered

carbonyl

Ketones and aldehydes

Carbonyl to alcohol

aldehyde

ketone

Amides are very common in drugs (e.g. ?) and ? amides are the most common

peptides, secondary

Relatively easy to form primary and secondary amides from

primary/secondary amines

Which of the following statements is false?

Peptide bonds are rigid and planar .

Peptide bonds can be broken through the action of peptidases.

A peptide bond is formed when the carboxyl group of one molecule reacts with the amino group of another molecule.

Peptide bonds link amino acids together in a peptide chain.

Peptide bonds are key features of drug targets.

Peptide bonds are unstable and readily hydrolysed in water.

Peptide bonds are unstable and readily hydrolysed in water.

Peptide bonds can be broken through the action of

peptidases

A peptide bond is formed when

the carboxyl group of one molecule reacts with the amino group of another molecule.

Peptide bonds link amino acids together in a

peptide chain.

Peptide bonds are key features of

drug targets

Peptide bonds are

rigid and planar

Proteases are enzymes that

cleave proteins and peptides

Substrate binding: the side-chain of the amino acid residue immediately before the scissile peptide bond can

bind to the recognition site on the enzyme

Protonation: His57 donates a proton to the amide nitrogen of the substrate, allowing

the release of the C- terminal portion of the peptide as a free peptide

G protein These receptors act like an inbox for cellular messages –

proteins, peptides, lipids, sugar, light energy

peptide bonds join the ? together to form ?, which fold into a ?(perhaps an enzyme)

amino acids, peptides, protein

Drug Targets- Enzymes

Primary Structure –

Peptide bond

Drug Targets- Enzymes

Secondary structure refers to

the spatial arrangement of amino acid residues that \n are near one another in the linear sequence

Polypeptide chains can fold into

regularly repeating structures, α

\-helices and β-sheets

X-ray crystallography is related to:

electron ionization

all answers are correct

photon reflections

magnetic field

ion abundance

photon reflections

Phytochemistry \n (Some) methods used: \n

•Thin layer chromatography (TLC) \n •Gel (column) chromatography \n •Gas chromatography (GC) \n •Mass spectrometry \n •Nuclear magnetic resonance \n • X-ray crystallography

Crystallography \n The information that you get are based on the analysis of the

diffraction patterns that emerge from a sample that is targeted by a beam of \n some type (like X-ray).

Diffraction is caused by

electron clouds:

the higher the atomic number of an element, the

larger it’s electron clouds are!

xray crystallography can determine

Stereochemistry \n Bond length \n Distance between atoms

Phytochemistry is the study of

phytochemicals produced in plants, describing \n the isolation, purification, identification, and structure elucidation of the large \n number of secondary metabolic compounds found in plants.

Magnetic field is related to

NMR.

Ion abundance and electron ionization are related to

mass spectrometry.

The toxicity of *Atropa belladonna* is due to:

none of the answers is correct

the function of atropine as an antagonist of gamma-butyric acid

the function of atropine as an agonist of acetylcholine

the function of atropine as an antagonist of acetylcholine

the function of atropine as an agonist of gamma-butyric acid

the function of atropine as an antagonist of acetylcholine

atropine extracted from belladonna is used in \n ? as a ?, to temporarily ? the ciliary muscle of \n the eye; and as a ?, to ? the pupils

ophthalmology, cycloplegic, paralyze, mydriatic, dilate

atropine acts as an ? of acetylcholine

antagonist

atropine acts as an antagonist of

acetylcholine

? acts as an antagonist of acetylcholine

atropine

What functional groups does molecule (i) contain?

A primary amine; an ester; a primary amide

A tertiary amine; an ester; a secondary amide

A secondary amine; a carboxylic acid; a secondary amide

A secondary amine; an ester; a secondary amide

A tertiary amine; a carboxylic acid; a primary amide

A primary amine; an ester; a carboxylic acid

A secondary amine; an ester; a secondary amide

carboxylic acid

primary secondary tertiary amide

ester

primary, secondary, tertiary amine

Molecules (i)-(iii) are active anti-parasitic drugs. Which of the following (a)-(g) represents the most likely active pharmacophore for (i)-(iii)?

(a)

(b)

(c)

(d)

(e)

(f)

(g)

a

Enzymes can reduce the “E factor” because:

all answers are correct

they operate at room temperature

they can overcome the need for organic solvents and other reagents

they can operate at ambient pressure

they are effective at mild pH values

they can overcome the need for organic solvents and other reagents

The "E factor" in Green Chemistry is defined as

 the ratio of kilograms of waste generated per kilogram of product synthesized.

A method used for separating a mixture of substances based on their different boiling points is called:

fractional distillation

thin layer chromatography

gas chromatography

partial solubilisation

fractional extraction

fractional distillation

The following mass spectrum is representative of:

a

b

c

d

e

c ("Fragments": C = 12; O = 16; CO = 28; CO2 = 44)

The production of new antibiotics by genetic manipulation of microorganisms is an example of:

red biotechnology

green biotechnology

grey biotechnology

white biotechnology

blue biotechnology

red biotechnology

A lone pair of electrons is:

always a strong hydrogen bond donor 

never a hydrogen bond acceptor 

always a weak hydrogen bond donor 

never a hydrogen bond donor or acceptor 

always a strong hydrogen bond acceptor

sometimes a strong hydrogen bond acceptor 

sometimes a strong hydrogen bond acceptor 

Which chemical functional group is not present in the following structure?

hydroxy group

ester

amide

carboxylic acid

aromatic ring

ester

Which one of the following molecules is likely to engage in important ionic binding interactions as a drug enters the target binding site?

(a)

(b)

(c)

(d)

(e)

(f)

b) drug - c = o - OH

In relation to drug optimisation strategies, which of the following statements is true?

***Ring contraction*** is not an example of a drug optimisation strategy. 

***Rigidification*** leads to a drug with a single active conformation.

***Simplification*** involves the systematic removal of functional groups in a drug.

***Simplification*** involves the systematic removal of chiral centres in a drug.

***Ring fusion*** allows the drug molecule to increase its number of active conformations. 

***Ring expansion*** is primerally used to increase the molecular weight of a drug molecule. 

***Simplification*** involves the systematic removal of functional groups in a drug.

ring expansion

a chemical reaction that involves the breaking and forming of covalent bonds to increase the size of a cyclic compound.

ring expansion can be achieved through various methods such as

heat, acid catalysis, or the use of specific reagents.

ring fusion

the process of joining two or more rings together to create a new compound with potentially unique properties.

ring fusion This technique is often used to modify the structure of existing drugs in order to

improve their efficacy or reduce their side effects.

rigidification

the process of making something rigid or stiff, often through the use of a hardening agent or by applying pressure.

ring contraction

a cyclic compound undergoes a rearrangement to form a smaller cyclic compound.

One common example of ring contraction is

the conversion of cyclohexanone to cyclopentanone through the use of acid catalysis.

***Simplification*** involves

the systematic removal of functional groups in a drug.

The interaction between tyrosine and phenylanine in a protein is an example of:

disulfide bond

a cation-pi interaction

pi-stacking

a ionic bond

a salt bridge

pi-stacking

pi-stacking

non-covalent interaction between aromatic rings, where the pi-electron clouds of the rings overlap and form a stabilizing interaction.

pi stacking is commonly observed in organic molecules, and plays a significant role in various biological processes such as

DNA replication and protein folding.

a cation-pi interaction

non-covalent interaction between a positively charged ion (cation) and an aromatic molecule with a pi electron cloud.

a cation-pi interaction This interaction is important in various biological processes, such as

protein-ligand binding and DNA-protein interactions.

disulfide bond

covalent bond between two sulfur atoms in two different amino acids within a protein molecule.

disulfide bond helps

stabilize the protein's three-dimensional structure.

By definition, an oral drug is always 100% bioavailable.

True

False

false

In an aqueous environment, an ionic interaction is most likely to take place between:

a protonated amine and a carboxylate 

a protonated amine and an alcohol

a protonated amine and an ester

a carboxylate and an alcohol

a carboxylate and an ester

an amide and a carboxylate

a protonated amine and a carboxylate 

One of the natural amino acids is not chiral because:

it is not superimposable with its mirror image

it does not have a mirror image

it is too small

it is not polar

two identical substituents are attached to the central carbon

two identical substituents are attached to the central carbon

When ?, the substance is not chiral.

two identical groups are attached to a tetrahedral carbon