MChem Exam 1

What ancient remedy was used by Greeks 2400 years ago for pain relief?

Willow leaves

In what year was salicin first crystallized?

1829

What significant advancement in salicylic acid occurred in 1899?

Hoffmann at Bayer acetylated salicylic acid to create Aspirin.

What is the significance of Qinghaosu (artemisinin) in medicine?

It is used to treat malaria and has saved millions of lives.

Who isolated Qinghaosu from the plant qinghao?

Chinese scientist Tu Youyou in 1972.

What prestigious award did Tu Youyou receive in 2015?

Nobel Peace Prize in Medicine.

What is morphine derived from and what is its primary use?

Derived from opium, used for pain relief.

Which plant is quinine derived from and what does it treat?

Derived from the bark of the cinchona tree, used to treat malaria.

What is paclitaxel (Taxol) and from which plant is it isolated?

A chemotherapy drug isolated from the bark of the Pacific yew.

What is the role of soil samples in drug discovery?

They provide sources for antimicrobial agents and immunosuppressants.

What are biologics?

Drugs made from living organisms, including proteins, carbohydrates, and nucleic acids.

How are drugs classified by pharmacological effect?

Grouped based on their biological effect, such as analgesics and antibiotics.

What is a drug?

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

What is a drug target?

A molecule associated with a disease process that a drug interacts with to produce a therapeutic effect.

What is the significance of covalent bonds in drug action?

They involve sharing electron pairs and can lead to long-lasting effects, but may have low specificity.

What is the octet rule in relation to drug molecules?

Atoms in a molecule must have 8 valence electrons to become stable.

What is the purpose of high-throughput screening in drug discovery?

To rapidly test natural and synthetic compounds for potential therapeutic effects.

What is the role of AI in drug discovery?

AI helps predict protein structures and accelerates scientific research.

What is structure-activity relationship (SAR) in medicinal chemistry?

The relationship between a drug's chemical structure and its biological activity.

What are some examples of drugs derived from fungi?

Penicillins, cephalosporins, and immunosuppressants like cyclosporin.

What is the function of antihistamine drugs?

They block or reduce the action of histamine in the body.

What is molecular docking in computer-aided drug design?

A method used to predict how a drug interacts with its target at the molecular level.

What can lead to prolonged adverse effects when drugs form irreversible bonds?

A lack of specificity and irreversible bonds.

What is alkylation in drug action?

A drug adds an alkyl group to its target, used in cancer treatment as alkylating antineoplastic agents.

What were the first alkylating agents used medically?

Nitrogen mustards, which were also the first modern cancer chemotherapies.

What is acylation in drug action?

A drug adds an acyl group to its target, involving functional groups like esters or amides.

How does aspirin function in acylation?

Aspirin acylates serine with an acetyl group at its target enzyme, COX.

What is the role of DD-transpeptidase?

It is a bacterial enzyme involved in bacterial cell wall biosynthesis, targeted by B-lactam antibiotics.

What is phosphorylation in drug action?

A drug adds a phosphate group to its target, often seen in organophosphates.

What is a significant characteristic of organophosphates?

They irreversibly phosphorylate acetylcholinesterase and are primarily used as insecticides.

What are non-covalent bonds in drug interactions?

Most drugs bind to their biological targets through non-covalent bonds, which are readily reversible.

What factors influence the strength of non-covalent bonds?

The distance between functional groups on the drug and the target, steric factors, and stereochemistry.

What types of interactions are classified as ionic bonds?

Electrostatic interactions between ionized acidic and basic functional groups.

What is the bond energy range for ionic bonds?

20-40 kJ/mol, making them the strongest among non-covalent bonds.

What defines dipole interactions?

They occur due to differences in electronegativity, creating partial charge separations.

What is the strength range of dipole-dipole interactions?

2-8 kJ/mol.

What characterizes hydrogen bonds?

A special dipole-dipole interaction involving a partially positively charged hydrogen atom and a highly electronegative atom.

What is the strength range of hydrogen bonds?

16-60 kJ/mol.

What are van der Waals interactions?

Interactions caused by temporary dipoles due to uneven electronic distribution, typically very weak (2-4 kJ/mol).

What are hydrophobic interactions?

Interactions that occur between non-polar molecules in aqueous environments, contributing to drug binding.

What are pi-pi stacking interactions?

Aromatic interactions important for binding, involving aromatic groups from both drug molecules and target proteins.

What is chelation in drug interactions?

Binding of ions and molecules to metal ions, forming coordination compounds.

How can chelation affect drug activity?

Some drugs chelate with Ca2+ and lose their activity.

What is the primary mechanism of action for tetracycline?

To inhibit protein synthesis by binding to the 30S ribosomal subunit.

Why should tetracycline and calcium not be taken together?

They can interfere with each other's absorption.

What is the primary mechanism of action for ciprofloxacin?

To inhibit bacterial DNA gyrase.

What are functional groups in organic chemistry?

Specific groupings of atoms within molecules that have characteristic properties and reactivity.

How do functional groups affect drug pharmacodynamics?

They provide properties that allow drugs to exert desired effects, including receptor binding and chemical interactions.

What does pharmacokinetics refer to?

What the body does to a drug, including absorption, distribution, metabolism, and excretion (AMDE).

What is the significance of the pKa value of a functional group?

It indicates the strength of the acid and its tendency to donate protons.

What is the charge of carboxylic acid under physiological conditions (pH=7.2)?

Negatively charged (carboxylate).

Name a drug that contains a carboxylic acid functional group.

Ibuprofen, Naproxen, or Diclofenac.

What is the basic functional group and its solubility characteristics?

Amines are polar and relatively water-soluble.

What is the pKa range for aniline's conjugate acid?

2-5.

What is the significance of resonance in functional groups?

Resonance occurs when electrons are shared among atoms with adjacent double bonds and lone pairs, affecting stability and reactivity.

What are electron donating groups?

Functional groups that donate electrons, such as phenol and aniline.

What are electron withdrawing groups?

Functional groups that attract electrons, such as aldehydes and carboxylic acids.

Define hydrophilic and hydrophobic molecules.

Hydrophilic molecules are attracted to water (polar), while hydrophobic molecules are attracted to oil (nonpolar).

What is the partition coefficient (P)?

A ratio of the concentrations of a molecule between two solvents, specifically for water and 1-octanol.

What is the effect of adding a functional group to a molecule?

It can affect the electronic, inductive, and solubility properties of the molecule.

What is the role of pharmacodynamics in drug action?

It describes what the drug does to the body, including its effects on drug targets.

What is the significance of the pKa of guanidines?

Guanidines have a pKa of 12, making them stronger bases than amines.

What is the relationship between pKa and the form of a conjugate acid?

A conjugate acid with a smaller pKa exists more in the base form, while one with a larger pKa exists more in the conjugate acid form.

What does log P indicate about a molecule?

Log P indicates the hydrophilicity or hydrophobicity of a molecule; lower log P values indicate more hydrophilic properties, while higher values indicate more hydrophobic properties.

How does log P affect drug behavior in the human body?

The log P of a drug affects its absorption, distribution, metabolism, and excretion (ADME) within the human body.

What is the significance of the human body's water content in relation to drug log P?

The human body contains about 60% water, which influences how hydrophilic or hydrophobic a drug will behave in the body.

What is the role of steric effects in drug binding?

Steric effects involve how the size and stereochemistry of a functional group can influence its binding at the target, potentially increasing or decreasing binding efficacy.

What are privileged scaffolds in drug design?

Privileged scaffolds refer to molecular frameworks that can produce biological activities across multiple biological systems and are often found in natural products and synthetic drugs.

How do enzymes function as drug targets?

Enzymes act as catalysts that speed up chemical reactions, providing a reaction surface and suitable environment for reactants to form a low-energy transition state.

What is the active site of an enzyme?

The active site is a specific region on the enzyme where substrates bind, characterized by a unique shape that allows only specific substrates to fit.

What is the Lock and Key hypothesis?

The Lock and Key hypothesis suggests that both the enzyme and substrate are rigid, fitting together like a key in a lock.

What is the Induced Fit hypothesis?

The Induced Fit hypothesis posits that the substrate can induce a change in the enzyme's shape to achieve a better fit.

What are competitive inhibitors?

Competitive inhibitors compete with substrates for the active site of an enzyme, often resembling the substrate's structure.

What are non-competitive inhibitors?

Non-competitive inhibitors bind to an allosteric site on the enzyme, not affecting substrate binding but inhibiting the enzyme's activity.

What is the medicinal use of penicillins?

Penicillins inhibit bacterial enzymes by acylating the active site of bacterial D-Alanine carboxypeptidase.

What role do kinases play in drug design?

Kinases catalyze the phosphorylation of proteins, playing a crucial role in regulating cell processes and serving as targets for anticancer drugs.

What are G protein-coupled receptors (GPCRs)?

GPCRs are a class of cell surface receptors that detect external molecules and activate internal signal transduction pathways.

What is the function of agonists in relation to GPCRs?

Agonists bind to GPCRs and activate them to produce a biological response, with full agonists eliciting maximum responses.

What is the role of antagonists in drug action?

Antagonists bind to receptors to block their function, inhibiting the action of agonists without changing the receptor's conformation.

What are nuclear receptors?

Nuclear receptors are ligand-induced transcription factors located inside cells that regulate gene expression by binding directly to DNA.

What percentage of FDA-approved drugs target nuclear receptors?

Approximately 13% of FDA-approved drugs target nuclear receptors.

What is the typical action of agonists on nuclear receptors?

Agonists usually upregulate gene expression when bound to their cognate nuclear receptors.

What are endogenous ligands?

Endogenous ligands are naturally occurring substances, such as hormones like estradiol and testosterone, that bind to receptors.

What is the role of an antagonist in pharmacology?

An antagonist blocks the effect of an agonist through competitive binding.

Which drugs target nuclear receptors?

Drugs such as corticosteroids, estrogens, androgens, and vitamin D target nuclear receptors.

What medical conditions can glucocorticoids treat?

Glucocorticoids can treat allergies (asthma), inflammation, and autoimmune disorders like rheumatoid arthritis.

What is the function of the estrogen receptor antagonist tamoxifen?

Tamoxifen is used in the treatment of breast cancer and infertility.

What are ion channels?

Ion channels are pore-forming membrane proteins that allow ions (Na+, K+, Ca2+, Cl-) to pass through.

What is the function of the GABAA receptor?

The GABAA receptor is a ligand-gated Cl-channel that opens to allow Cl- to flow through when activated by GABA.

What is a Positive Allosteric Modulator (PAM)?

A PAM enhances the receptor's activity without activating it, such as benzodiazepine binding to the GABAA receptor.

What is the use of flumazenil?

Flumazenil is a Negative Allosteric Modulator (NAM) used to treat benzodiazepine overdose.

What is the primary structure of nucleic acids?

Nucleic acids (DNA and RNA) are formed by linking nucleotides through phosphodiester bonds.

What components make up a nucleotide?

A nucleotide consists of a base (Adenine, Guanine, Cytosine, Thymine, Uracil), a 5-carbon sugar (ribose or deoxyribose), and one or more phosphate groups.

What is the function of mRNA?

mRNA copies genetic information from DNA and carries it to ribosomes for protein synthesis.

How do intercalating agents affect DNA?

Intercalating agents insert between DNA base pairs, disrupting hydrogen bonds and altering the double helix shape.

What is the role of DNA topoisomerases?

DNA topoisomerases are enzymes that manage DNA overwinding and underwinding during replication.

What are antisense oligonucleotides (ASO)?

ASOs are single strands of DNA or RNA that bind to mRNA to prevent protein translation.

What is the significance of chirality in molecules?

Chirality refers to molecules that cannot be superimposed on their mirror images, which can affect their biological activity.

What are stereoisomers?

Stereoisomers are compounds with the same molecular formula but different stereochemical arrangements.

How are S and R designations assigned to chiral centers?

Priorities are assigned to substituents based on atomic number; the arrangement determines if the configuration is S (counterclockwise) or R (clockwise).