00126 - Medicinal and Toxicological Chemistry I;

Learning outcomes

By the end of the course, the student should have a good understanding of the mechanistic aspects of the drugs and in particular about the different kind of bonds and the steric factors involved in the drug-target interactions. During the course the principal drugs families which interact both with targets located in the host cell and with neurotransmitters receptors will be addressed. About these drugs, structure-activity relationships (SAR), therapeutic utilization, and their related chemical-toxicological aspects will be described.

Course contents

GENERAL PART
Molecular mechanisms of Drug action. Principles of drug pharmacokinetics: drug absorption, drug distribution, drug metabolism (Phase I and Phase II reactions), drug excretion. Drug target interactions: description of different chemical bonds involved in. Influence of steric factors on drugs activity: optical (chirality), geometric and conformational isomery. Bioisosterism. Enzymatic inhibition: competitive and non-competitive inhibitors. Transition-state analogues.
Receptors: basic principles of receptor theory. Intracellular and membrane receptors.

SPECIFIC TOPICS
CHEMIOTERAPEUTICS: definition, general aspects

Antibiotics which interfere with the biosynthesis of the cellular wall : beta-lactams antibiotics (chemical structure and nomenclature; mode of action). Penicillins, Cephalosporins,Thyenamycins, Imipenem, Nocardicins, Monobactams, clavulanic acid, Sulbactam, Fosfomycin, Glicopeptides.
Antibiotics which interfere with the protein transcription : Ansamycins .
Antibiotics which interfere with the protein transduction : Macrolides, Chloramphenicol, Oxazolidinones, Aminoglycosides, Tetracyclines
DNA gyrase inhibitors : Quinolones
Ihnibitors of the dihydropteroate synthase: Sulphamidics
Inhibitors of the dihydrofolate reductase: Structure and biological role of the folic acid, classical and non-classical inhibitors, selective toxicity. SAR.

ANTIMALARIC DRUGS.

ANTIMYCOTICS DRUGS: natural antimycotics : Griseofulvin, Macrolides Polyenes (Structure and mode of action). Chemical antymicotics: Azoles, Allylammines, thiocarbammates, 5-Fluorocitosine.

ANTIVIRAL DRUGS: DNA polymerase inhibitors. mRNA synthesis inhibitors. Inhibitors of viral penetration. Reverse transcriptase inhibitors. Protease inhibitors.

ANTICANCER DRUGS: Alkylating drugs. Antimetabolites. Intercalators. Topoisomerase I and II inhibitors. Mitotic inhibitors. Kinase inhibitors.

ARACHIDONIC ACID CASCADE: prostaglandins, thromboxanes and leukotrienes.
NON STEROIDAL ANTINFLAMMATORY DRUGS: mode of action, SAR, pharmacological profile, (COX 1 and COX 2 selectivity).

DRUGS ACTING ON CNS.

SEDATIVE-HYPNOTICS: Benzodiazepines

ANTIEPILECTIC DRUGS: Drugs acting on ion channels, Drugs acting on GABAergic system.

ANTIPARKINSON DRUGS: Biological role of dopamine. Dopaminergic agonists, Dopa-decarboxylase inhibitors, MAO-B inhibitors, COMT inhibitors.

NEUROLEPTICS: Typical antipsychotic: Phenothiazines (Structure, mode of action, SAR, analogues, synthesis). Butyrophenones. Benzamides. Reserpine and analogues. Atypical antipsychotics.

ANTIDEPRESSANT DRUGS : MAO inhibitors. Tricyclic antidepressants endowed with 6,7,6 cycle (structure, mode of action, synthesis). Selective biological amines reuptake inhibitors.

OPIOID ANALGESICS: morphine, morphinanes, benzomorphans, 4-phenylpiperidines and phenylpropylamines; partial agonists and antagonists.

EXERCISE ACTIVITIES
Drug design and innovative synthetic strategies.
Presentation of case histories

Readings/Bibliography

Class attendance (mandatory) with the related power point presentations are part of the teaching material.

Readings

A. GASCO, F. GUALTIERI, C. MELCHIORRE, Chimica Farmaceutica, CEA, Milano, 2020 (second edition)

D.A. WILLIAMS, T.L. LEMKE, Foye's Principi di Chimica Farmaceutica, VI Edizione italiana, Piccin, Padova, 2014.

T.L. LEMKE, S.W. ZITO, V.F. ROCHE, D.A. WILLIAMS, Foye's Principi di Chimica Farmaceutica: L’ ESSENZIALE, I Edizione italiana, Piccin, Padova, 2017.

G.L. PATRICK, Introduzione alla Chimica Farmaceutica, II Edizione italiana, EdiSES, Napoli, 2013.

Teaching methods

Lectures in the classroom with power point presentations. Group exercises concerning the exam topics.

Assessment methods

Students attending the lessons can take an optional midterm test during the first semester (January) lasting 120 minutes. The object of the test is chemotherapy drugs (excluding anticancer drugs).The ongoing test includes 3 open questions related to course topic. The minimum grade to pass the test is 18/30. Students who pass the test in progress can take the final oral exam by December 30 of the year of attendance, without answering the questions present in the midterm test.

Students who do not take the mid-term exam will take a final oral exam.

Teaching tools

Video projector - PC system - connection to specific websites.
The slides presented in class are made available to the student in electronic format, on the online support platform virtuale.unibo.it. Username and password are reserved for students enrolled at the University of Bologna.

Office hours

See the website of Marinella Roberti