Med Chem E1 Redo

Where does Aspirin come from?

Willow leaves

Where did Artemisinin come from? Treat?

Qinghao plant; treats malaria

Where did Morphine come from? Treat?

Opium plant; pain relief

Where did Quinine come from? Treat?

Bark of cinchona; malaria

Where is Digitoxin from? Treatment

Foxglove; heart failure

Where is Paclitaxel from? Treatment?

From bark of Pacific yew; Cancers

Where is Camptothecin from? Treatment?

From bark and stem of camptotheca acuminata; Cancers

Which anti-infectives are derived from the soil sample (bacteria and fungi)

Streptomycin, Rifamycin, rapamycin

What antimicrobial drugs can come from soil microorganisms?

Streptomycin and rifamycin.

What immunosuppressant comes from soil microorganisms?

Rapamycin.

Which anti-infectives are derived from fungi

Vinblastine, Vincristine, cyclosporin, penicillins, cephalosporin

What antimicrobial drug classes are produced by fungi?

Penicillins and cephalosporins.

What immunosuppressant is produced by fungi?

Cyclosporin.

What anticancer drugs are associated with fungal sources?

Vinblastine and vincristine.

Which anti-infectives are derived from marine organisms

Vidarabine, Trabectedin

What antiviral drug was obtained from a Caribbean sponge?

Vidarabine.

What anticancer drug was obtained from a sea squirt?

Trabectedin.

What are the major natural sources used in drug discovery?

Soil samples, plants, and marine organisms.

What methods can isolate compounds from natural sources?

Extraction and chromatographic separation.

What are common synthetic approaches used in drug discovery?

Combinatorial chemistry, parallel synthesis, and focused libraries.

What does the R group represent in this morphine SAR?

The substituent replacing the phenolic OH at the 3-position.

How does substituting morphine’s phenolic OH affect affinity for the μ-opioid receptor (MOR)?

Affinity decreases.

Why is the phenolic OH group of morphine important?

It is crucial for morphine’s affinity for the mu-opioid receptor.

What can happen when the phenolic OH group of morphine is modified?

Opioid receptor affinity and activity decrease.

What happens to agonism as certain morphine substitutions increase in size?

Agonism decreases.

What may happen to antagonism as certain morphine substitutions change?

Antagonism increases.

List the N-substituents shown in order of increasing alkyl size.

Methyl → ethyl → propyl → butyl → pentyl → hexyl.

What does “zero activity” mean for an opioid ligand?

It has no agonist activity; it functions as an antagonist. Butyl

What are biologics?

Drugs from living organisms used to prevent, diagnose, or treat diseases

What types of molecules can biologics be made of?

Proteins, carbohydrates, nucleic acids, or combinations of these.

How do biologics generally compare with small-molecule drugs?

They are relatively larger and more complex.

What are three examples of biologics?

Antibodies, interleukins, and vaccines.

How can drugs be classified?

Pharmacological Effect

Chemical structure

Target System

Site/mechanism of action

Which drugs are grouped on effect

Analgesics, antibiotics, anti-cancer, anti-hypertensives, antipsychotics

Can drugs in the same pharmacological class have different mechanisms of action?

Yes.

Which drugs are grouped based off of chemical structure

Penicillins, barbiturates, opiates, steroids, and catecholamines.

What are drugs grouped by target system?

cholinergic drugs and antihistamines

What do cholinergic drugs do?

They inhibit, enhance, or mimic acetylcholine.

What is acetylcholine’s major role?

It functions as a neurotransmitter in the brain and body.

Which method of drug classification is the most specific?

By site/mechanism of action

What are drugs grouped by site/mechanism of action?

Drugs grouped based on the specific enzyme or receptor they interact with.

What is a drug?

A chemical substance of known structure that produces a biological effect when administered to a living organism.

What can drugs be used for?

To treat, cure, prevent, or diagnose disease or promote well-being.

What type of compound is a drug usually?

An organic compound.

What is a drug target?

A molecule in the body associated with a disease process that a drug can act on to produce a therapeutic effect.

What are the major types of drug targets?

Proteins (enzyme, receptor, channel) and nucleic acids (DNA, RNA)

What must a drug do to produce a therapeutic effect?

Bind to its target; bound

What happens when a drug (I) binds to its target (E)?

It forms a drug-target complex (E–I).

What effect can a drug-target complex have on its target?

It can change the target’s conformation.

How does the energy of a drug-target complex compare with free drug plus free target?

The drug-target complex has lower energy.

What are the four covalent drug-target interactions?

Alkylation, acylation, phosphorylation, and rearrangement.

What non-covalent interactions are listed?

Ionic, dipole, van der Waals, hydrophobic, and aromatic interactions.

What is a covalent bond?

A bond involving the sharing of electron pairs between atoms.

What is the geometry of an sp3-hybridized carbon?

Tetrahedral.

What is the geometry of an sp2-hybridized carbon?

Trigonal planar.

What is the geometry of an sp-hybridized carbon?

Linear

Do most drugs form covalent bonds with their biological targets?

No. Only a small number of drugs act by forming covalent bonds with their targets.

Are covalent drug-target bonds readily reversible?

No

What is a potential problem with covalent drugs having a long duration of action?

Their effects may last too long for the therapeutic indication.

What can low specificity and irreversible covalent bonding cause?

Prolonged adverse effects.

Why might some irreversible covalent drugs need special handling?

They are highly reactive.

What is alkylation?

A drug adds an alkyl group (CnH2n+1–) to its target.

What DNA base can be targeted by alkylating drugs?

Guanine.

What are alkylating drugs commonly used to treat?

Cancer.

What were the first alkylating agents used medically and the first modern cancer chemotherapies?

Nitrogen mustards.

What is acylation?

A drug adds an acyl group (RCO–) to its target.

What functional groups may be present in a drug that acylates its target?

Ester, lactone, amide, or carbamate groups.

What type of target atom is needed for acylation?

A nucleophilic N, S, or O atom.

How does aspirin act through acylation?

It transfers an acetyl group to a serine residue on COX.

Which antibiotics act through acylation of their target enzyme?

Beta-lactam antibiotics, including penicillins and cephalosporins.

What enzyme is acylated by beta-lactam antibiotics?

DD-transpeptidase.

What is the role of DD-transpeptidase in bacteria?

It is involved in bacterial cell-wall biosynthesis.

What does acetylcholinesterase do?

An enzyme that catalyzes the hydrolysis of acetylcholine

Are the acetylcholinesterase inhibitors reversible or irreversible?

Reversible.

What is phosphorylation in drug action?

Adds a phosphate group, irreversible very toxic

What are organophosphates primarily used as?

Insecticides.

When do rearrangement reactions usually occur?

During drug metabolism.

What can happen after a drug forms an active metabolite through rearrangement?

The active metabolite can form a covalent bond with a target protein.

How do most drugs bind to their biological targets?

By non-covalent bonds.

What determines the overall strength of non-covalent drug binding?

The sum of all individual non-covalent interactions.

What is the relationship between non-covalent binding strength and affinity?

Stronger overall binding means greater affinity for the target.

Are non-covalent drug-target interactions reversible?

Yes.

How does distance affect non-covalent bond strength?

Bond strength is inversely proportional to the distance between complementary drug and target groups.

What structural factors are important for drug-target non-covalent interactions?

Steric factors and stereochemistry.

What are ionic bonds in drug-target interactions?

Electrostatic interactions between oppositely charged groups.

Which non-covalent interaction is generally the strongest?

Ionic/electrostatic interactions.

What determines whether ionic bonds form at a given physiological pH?

The pKa of the functional groups.

When pKa is less than pH, what form does an acid mainly exist as?

The deprotonated form, A–.

When pKa is greater than pH, what form does a base mainly exist as?

The protonated form, BH+.

What is electronegativity?

The tendency of an atom to attract shared electrons toward itself.

Which has greater energy: ion-dipole or dipole-dipole interactions?

Ion-dipole interactions.

What is a dipole?

A separation of positive and negative charge within a system.

What happens to dipole moment as electronegativity difference increases?

The dipole moment increases.

What is a hydrogen bond?

A special dipole-dipole interaction between a partially positive H bonded to F, O, or N and a partially negative F, O, or N atom.

What are van der Waals interactions?

Weak interactions caused by temporary or induced dipoles from uneven electron distribution.

Can van der Waals interactions occur between any atoms or molecules?

Yes.

Why can van der Waals interactions be important despite being weak individually?

Many van der Waals interactions together can make a crucial contribution to binding.

What are pi-pi stacking interactions?

Interactions between an aromatic group on a drug and an aromatic group on a target.

What are cation-pi interactions?

Interactions between a positively charged group and an aromatic group.

What is chelation?

The bonding of ions and molecules to metal ions.