Medicinal Chemistry

Medicinal Chemistry Question & Answers by Dr. S. C. Khadse

Drug targets Q: What type of molecule is the following structure? • a) A protein • b) A nucleic acid • c) A phospholipid • d) A carbohydrate

Q: Which of the following is an accurate description of the phospholipidbilayer in cell membranes? • a) It is made up of two layers of phospholipid polymers. • b) It is made up of two layers of phospholipid molecules with the tails pointing away from each other. • c) It is made up of two layers of phospholipid molecules with the tails lying parallel to each other. • d) It is made up of two layers of phospholipid molecules with the tails interacting with each other.

Q: Which of the following statements is true regarding the phospholipidbilayer in cell membranes? • a) Water and ions are unable to cross the bilayer due to the charges present in the head groups. • b) Water and ions are unable to cross the bilayer due the hydrophobic tails of the phospholipid molecules. • c) Water and ions are encouraged to cross the bilayer by interacting with the charges present in the head groups. • d) The molecules in the bilayer are fluid, and so the cell membrane is porous allowing the passage of ions and water across the cell membrane.

Q: Which of the following statements is true? a) Drugs and drug targets generally have similar molecular weights. b) Drugs are generally smaller than drug targets. c) Drugs are generally larger than drug targets. d) There is no general rule regarding the relative size of drugs and their targets.

Q: What is meant by a binding site? a) The area of a macromolecular target that is occupied by a drug when it binds. b) The portion of the drug to which a drug target binds. c) The functional groups used by a drug in binding to a drug target. d) The bonds involved in binding a drug to its target.

Q: Consider the molecule in blue bound to a binding site. Identify the binding interactions taking place at i and iv, ii, & iii shown in red. • a) hydrogen bonds • b) ionic bonds • c) van der Waals interactions

Q: Which of the following binding interactions is likely to be the most important initialinteraction when a drug enters a binding site? • a) van der Waals interactions • b) hydrogen bond • c) ionic • d) induced dipole-dipole interactions

Q: Which of the following underlined atoms is likely to be the strongest hydrogen bond acceptor? a) amide nitrogen (RNHCOR') b) aniline nitrogen (ArNH2) c) amine nitrogen (RNH2) d) carboxylate oxygen (RCO 2-)

Q : Which of the following underlined protons is likely to be the strongest hydrogen bond donor? a) alcohol (ROH) b) amine (RNH2) c) phenol (ArOH) d) ammonium ion (RNH3+)

Q : Which of the following functional groups is most likely to participate in a dipole-dipole interaction? a) Aromatic ring b) Ketone c) Alcohol d) Alkene

Q : Which of the following statements is untrue? a) Desolvation is an energy expensive process that involves the removal of water from polar functional groups prior to a drug binding to its binding site. b) Water molecules surrounding a hydrophobic region of a drug form an ordered layer of molecules with low entropy. c) Interaction between the non-polar regions of a drug and the non-polar regions of a target require the removal of an ordered water coat and represents a gain in binding energy due to increased entropy. d) An increase in entropy results in a greater positive value of ΔG and a greater chance of binding.

Receptors Q : Which of the following statements is not true about receptors? a) Most receptors are proteins situated in the cell membrane. b) Receptors contain a hollow or cleft on their surface which is known as a binding site. c) Receptors bind chemical messengers such as neurotransmitters or hormones. d) Receptors catalyse reactions on chemical messengers.

Q: Which of the following statements is not true about neurotransmitters? a) Neurotransmitters are released by nerves. b) Neurotransmitters are required to carry a 'message' from a nerve to a target cell. c) Neurotransmitters have significant distances to cover to reach their target cells. d) Neurotransmitters bind to receptors on target cells.

Q: Which of the following is not a neurotransmitter? a) acetylcholine b) cyclic AMP c) noradrenaline d) dopamine Q : Which of the following statements is not true regarding the binding site of a receptor? a) The binding site is normally a hollow or cleft in the surface of a receptor. b) The binding site is normally hydrophobic in nature. c) Chemical messengers fit into binding sites and bind to functional groups within the binding site. d) The binding site contains amino acids which are important to the binding process and a catalytic mechanism.

Q : Which of the following statements is not true about a ligand-gated ion channel receptor? a) Ligand-gated ion channel receptors are present in the cell membrane. b) Neurotransmitters can act as the chemical messengers for ligand-gated ion channels. c) Ligand-gated ion channels consist of five glycoproteins. d) Differences in membrane potential affect whether ligand-gated ion channel receptors open or close.

Q : Which of the following statements is true about a G-protein coupled receptor? a) It contains five transmembrane hydrophobic sections. b) There are more extracellular loops than intracellular loops. c) The binding region for the G-protein involves two extracellular loops. d) The N-terminal chain is extracellular and the C-terminal chain is intracellular. Q : Which of the following is not a G-protein coupled receptor? a) the muscarinic receptor b) the glycine receptor c) the adrenergic receptor d) the glutamate receptor

Q: Which of the following statements is not true about G-protein coupled receptors? a) They generally mediate the action of fast acting neurotransmitters. b) They mediate the action of some hormones. c) They activate signal proteins called G-proteins. d) Histamine can act as a ligand for some G-protein coupled receptors. Q: Which of the following pairs of receptors are likely to show the greatest structural similarity? a) the dopamine receptor subtypes D3 and D5 b) the M2 muscarinic receptor and the β2-adrenergic receptor c) the H2 histamine receptor and the α1-adrenoceptor d) the H1 histamine receptor and the β2 adrenoceptor

Receptors as drug targets Q: Which of the following terms is used to describe a drug that has the same effect on a receptor as the endogenous chemical messenger? a) agonist b) antagonist c) partial agonist d) inverse agonist Q Which of the following terms is used to describe a drug that binds to a receptor, fails to activate it and prevents the endogenous chemical messenger from binding? a) agonist b) antagonist c) partial agonist d) inverse agonist

Q. Which of the following is not a crucial requirement for a drug to act as an agonist? a) Functional groups b) Metabolic stability c) Pharmacophore d) Size Q. Which of the following terms applies to the maximum biological effect resulting from a drug binding to its target? a) affinity b) efficacy c) potency d) stability

Q. Which of the following terms applies to the amount of drug required to produce a defined biological effect? a) affinity b) efficacy c) potency d) stability Q. When an agonist binds to a receptor for a long period of time, it can result in a phosphorylation reaction occurring, Which of the following terms is the most relevant description of the immediate effect? a) Tolerance b) Dependence c) Sensitization d) Desensitization

Drug discovery: finding a lead Q. What is meant by a lead compound in medicinal chemistry? a) A drug containing the element lead. b) A leading drug in a particular area of medicine. c) A compound that acts as the starting point for drug design and development. d) A drug which is normally the first to be prescribed for a particular ailment. Q. Which of the following needs to be established before the search for a lead compound takes place? a) the pharmacophore b) Structure-activity relationships c) a bioassay d) patents

Q. There are several sources and methods of discovering new compounds. Which of the following is most likely to lead to the discovery of a complex structure quite unlike any other previously discovered? a) combinatorial chemistry b) database mining c) screening plant extracts d) me too drugs Q. Which source has been particularly fruitful in finding novel antitumour agents such as bryostatins and dolostatins? a) marine sources b) venoms and toxins c) combinatorial chemistry d) animals

Q. Which of the following drugs was not isolated from a natural source? a) quinine b) morphine c) isoniazid d) artemisinin Q. Natural products are often used as lead compounds in the design and synthesis of novel drugs. Which of the following general characteristics of a natural product is most likely to be a disadvantage in synthesising analogues? a) novelty of structure b) complexity of structure c) level of activity d) availability

Adrenergic drugs Q. Which of the following is a natural chemical messenger for the adrenergic receptor? a) Acetylcholine b) Dopamine c) Serotonin d) Noradrenaline Q. What is the predominant adrenoceptor in heart muscle? a) α1-adrenoceptor b) α2-adrenoceptor c) β1-adrenoceptor d) β2-adrenoceptor

Q. What is the predominant β-adrenoceptor in bronchial smooth muscle? a) β1-adrenoceptor b) β2-adrenoceptor c) β3-adrenoceptor d) β4-adrenoceptor Q. What is the main clinical use for agonists of the β2-adrenoceptor? a) Treatment of angina b) Treatment of hypertension c) Treatment of asthma d) Treatment of pain

Q. Salbutamol is an important clinical agent. The coloured groups are modifications that distinguish the molecule from adrenaline or noradrenaline. What role does the t-butyl group play? a) It acts as steric shield to reduce metabolism b) It increases hydrophobicity such that the molecule can cross cell membranes c) It introduces selectivity for β-adrenoceptors d) It introduces selectivity for α-adrenoceptors

Q. Salbutamol is an important clinical agent. The coloured groups are modifications that distinguish the molecule from adrenaline or noradrenaline. Why was the hydroxymethylene group introduced? a) It was a chain extension to place the OH group closer to its binding region in the binding site b) It was introduced to increase the area of conformational space available to the OH group c) It was introduced to reposition the phenol OH such that it was not recognised by metabolic enzymes d) It was introduced to reduce the electronic influence of the OH group on the aromatic ring

Q. The following diagram illustrates some of the compounds that were involved in the development of the important clinical agent - propranolol. What effect does the naphthalene ring have? a) It makes the agent an agonist b) It makes the agent an antagonist c) It makes the agent a partial agonist d) It makes the agent inactive

Q. The diagram below indicates some of the groups present in propranolol. How does the alcohol group interact with the binding site? a) By ionic interactions b) By hydrogen bonding c) By van der Waals interactions d) It remains solvated and has no interactions

Q. The diagram below indicates some of the groups present in propranolol. How does the ether group interact with the binding site? a) It has no interactions and remains solvated b) By hydrogen bonding as a hydrogen bond donor c) By van der Waals interactions d) By hydrogen bonding as a hydrogen bond acceptor

Medicinal Chemistry