Physicochemical properties and drug design. Pharmacodynamics (drug-receptor and drug-enzyme interaction). The drug discovery process. Carbonic anhydrases as example of druggable target. Antiviral drugs. Antibacterials and fighting resistance to antibiotics. NSAIDs. Protease inhibitors. Anti-Alzheimer drugs/strategies. Proton pump inhibitors. Tyrosine kinase inhibitors. Hypoxia/tumor acidification in the design of novel antitumor agents and diagnostic tools. Computational tool in drug discovery.
Chimica farmaceutica. A. Gasco, F. Gualtieri, C. Melchiorre eds, Casa Editrice Ambrosiana 2020
Chimica Farmaceutica II - Farmaci Sistemici, E. Novellino Ed., Università Federico Secondo Napoli.
Foye's Principle of Medicinal Chemistry, VII italian edition, PICCIN 2021
Learning Objectives
The student is expected to become familiar with the chemical aspects of drug action and drug discovery
Prerequisites
-
Teaching Methods
Lectures; lab practice with molecular modeling softwares
Further information
The teaching material will be available from the Moodle e-learning platform
Type of Assessment
Oral examination. 2/3 questions to verify the knowledge of the student
Course program
Part 1 (Basic Medicinal Chemistry): Introduction to medicinal chemistry. Structural properties and drug action: optical, geometrical and conformational isomerism. Atropisomerism. Bioactive conformation. Chiral switch. Physicochemical properties (ionization, acidity, solubility, Partition Coefficient, Distribution Coefficient). Reversible and irreversible interactions between drugs and biological macromolecules. and The fate of drugs in the body: absorption, distribution (binding to plasma protein, biological barriers), metabolism (phase I and II reactions, toxic metabolites; factor affecting metabolism), excretion. Pharmacodynamics (drug-receptor and drug-enzyme interaction). The organization and function of receptor systems; orthosteric and allsosteric ligands; potency, affinity and efficacy. The drug discovery process: lead generation and optimization.
Part 2 (Systematic Medicinal Chemistry): Carbonic anhydrases as example of druggable target in many pharmacological fields. Antivirals (HSV, HIV, influenza virus, SARS-CoV-2, etc.). Antibacterials and fighting resistance to antibiotics (dihydropteroate synthase (sulfa drugs) and dihydrofolate reductase inhiibtors). NSAIDs. Proteases as drug targets and their inhibition (ACE, serine proteases involved in blood coagulation, MMPs, etc.). Anti-Alzheimer drugs/strategies. Proton pump inhibitors. Anticancer drugs belonging to the tyrosine kinase inhibitors. Hypoxia/tumor acidification in the design of novel antitumor agents and diagnostic tools
Laboratory practice: Computational tool in drug discovery: structure-based and ligand-based methods. Case studies applied to modern drug development.