General Objectives.
The general objective of the MEDICINAL AND TOXICOLOGICAL CHEMISTRY I course is to provide students with the rational foundations of modern medicinal chemistry, providing the specific chemical knowledge underlying the therapeutic action of drugs. The course is divided into two parts, including general medicinal chemistry and systematic medicinal chemistry. The general medicinal chemistry section analyzes the concepts and strategies for rational drug discovery and design, as well as the rules used in drug nomenclature. Knowledge of the pharmaceutical and pharmacokinetic phases allows for an understanding of the drug's pathway within the human body, from absorption to distribution to elimination through the excretory system. The study of the pharmacodynamic phase covers the various types of drug molecular targets, the interactions involved, and the consequences of these interactions. The systematic medicinal chemistry section covers the main classes of natural and synthetic antibacterial drugs (sulfonamides, quinolones, nitrochemotherapeutics, peptidoglycan synthesis-inhibiting antibiotics, penicillins, cephalosporins, carbapenems, ribosome-inhibiting antibiotics, aminoglycosides, macrolides, tetracyclines, chloramphenicol, and ansamycins), antimycobacterial, antifungal, antiviral, anticancer, disinfectant, and topical anti-infective agents. Within each class, particular emphasis is placed on drug discovery and development, molecular mechanisms of action, the relationship between chemical structure and biological activity, the study of pharmacokinetic properties, the main therapeutic uses, toxicity profiles, potential interactions with other xenobiotics, and the synthesis of representative drugs. Upon completion of the course, students will possess the chemical knowledge underlying the therapeutic action of drugs. Students will be able to follow the drug design and development phases, understand drug absorption and distribution in the body, target interaction, metabolism, and excretion. The course will provide students with the chemical basis of the mechanism of action of each drug class covered and an understanding of the molecular modifications that influence the duration of action, routes of administration, and spectrum of action, and can improve clinical efficacy and safety. Students will also gain knowledge of the synthetic pathways leading to the production of some of the drugs covered in the course, especially with regard to production costs.
Specific Objectives
1. Student Knowledge and Understanding (Dublin Descriptor 1) The student will know and be able to understand all the main issues and strategies of drug discovery and rational design, the pharmaceutical, pharmacokinetic, and pharmacodynamic phases of drug action, the synthetic issues in drug preparation, and the main classes of antibacterial, antimycobacterial, antifungal, antiviral, antitumor, disinfectant, and topical anti-infective drugs.
2. Ability to Apply Knowledge and Understanding (Dublin Descriptor 2) At the end of the course, the student, applying the knowledge acquired, will be able to recognize a drug and classify it into one of the above categories, evaluate the structural variations within a drug class that improve or worsen its activity, and modulate absorption and duration of action. The student will be able to plan the synthesis of a specific drug or biologically active molecule. He or she will be able to apply this knowledge to hypothesize the interaction modes of a specific drug with its molecular target.
(Dublin descriptors 3, 4, 5 – soft skills)
3. Critical thinking and judgment skills (lab tests, written reports, etc.) By the end of the course, students will be able to evaluate the choice of a drug based on its chemical structure. This critical thinking and judgment will be developed through the ongoing interactivity offered during the course. The instructor will continuously ask students questions to stimulate them and develop their critical thinking. These questions will also serve to evaluate and encourage students to make connections with everything previously studied, avoiding considering the study of the material an exercise, but integrating the material in light of the knowledge already acquired.
4. Ability to communicate what has been learned. The student's evaluation will be assessed solely through an oral exam, which will cover all the topics of the program, testing the student's ability to communicate what they have learned.
5. Ability to continue studying independently. Students will find in-depth coverage of what they learned in class in the recommended textbooks and in scientific literature and will be able to use them to continue their studies independently. This will help them recall the topics covered even in the future, even when their memory of the concepts taught in class has faded. The textbooks will remain a point of reference for the student, who will know where to go to revisit in detail the concepts acquired in the past, some of which have inevitably been forgotten.
The general objective of the MEDICINAL AND TOXICOLOGICAL CHEMISTRY I course is to provide students with the rational foundations of modern medicinal chemistry, providing the specific chemical knowledge underlying the therapeutic action of drugs. The course is divided into two parts, including general medicinal chemistry and systematic medicinal chemistry. The general medicinal chemistry section analyzes the concepts and strategies for rational drug discovery and design, as well as the rules used in drug nomenclature. Knowledge of the pharmaceutical and pharmacokinetic phases allows for an understanding of the drug's pathway within the human body, from absorption to distribution to elimination through the excretory system. The study of the pharmacodynamic phase covers the various types of drug molecular targets, the interactions involved, and the consequences of these interactions. The systematic medicinal chemistry section covers the main classes of natural and synthetic antibacterial drugs (sulfonamides, quinolones, nitrochemotherapeutics, peptidoglycan synthesis-inhibiting antibiotics, penicillins, cephalosporins, carbapenems, ribosome-inhibiting antibiotics, aminoglycosides, macrolides, tetracyclines, chloramphenicol, and ansamycins), antimycobacterial, antifungal, antiviral, anticancer, disinfectant, and topical anti-infective agents. Within each class, particular emphasis is placed on drug discovery and development, molecular mechanisms of action, the relationship between chemical structure and biological activity, the study of pharmacokinetic properties, the main therapeutic uses, toxicity profiles, potential interactions with other xenobiotics, and the synthesis of representative drugs. Upon completion of the course, students will possess the chemical knowledge underlying the therapeutic action of drugs. Students will be able to follow the drug design and development phases, understand drug absorption and distribution in the body, target interaction, metabolism, and excretion. The course will provide students with the chemical basis of the mechanism of action of each drug class covered and an understanding of the molecular modifications that influence the duration of action, routes of administration, and spectrum of action, and can improve clinical efficacy and safety. Students will also gain knowledge of the synthetic pathways leading to the production of some of the drugs covered in the course, especially with regard to production costs.
Specific Objectives
1. Student Knowledge and Understanding (Dublin Descriptor 1) The student will know and be able to understand all the main issues and strategies of drug discovery and rational design, the pharmaceutical, pharmacokinetic, and pharmacodynamic phases of drug action, the synthetic issues in drug preparation, and the main classes of antibacterial, antimycobacterial, antifungal, antiviral, antitumor, disinfectant, and topical anti-infective drugs.
2. Ability to Apply Knowledge and Understanding (Dublin Descriptor 2) At the end of the course, the student, applying the knowledge acquired, will be able to recognize a drug and classify it into one of the above categories, evaluate the structural variations within a drug class that improve or worsen its activity, and modulate absorption and duration of action. The student will be able to plan the synthesis of a specific drug or biologically active molecule. He or she will be able to apply this knowledge to hypothesize the interaction modes of a specific drug with its molecular target.
(Dublin descriptors 3, 4, 5 – soft skills)
3. Critical thinking and judgment skills (lab tests, written reports, etc.) By the end of the course, students will be able to evaluate the choice of a drug based on its chemical structure. This critical thinking and judgment will be developed through the ongoing interactivity offered during the course. The instructor will continuously ask students questions to stimulate them and develop their critical thinking. These questions will also serve to evaluate and encourage students to make connections with everything previously studied, avoiding considering the study of the material an exercise, but integrating the material in light of the knowledge already acquired.
4. Ability to communicate what has been learned. The student's evaluation will be assessed solely through an oral exam, which will cover all the topics of the program, testing the student's ability to communicate what they have learned.
5. Ability to continue studying independently. Students will find in-depth coverage of what they learned in class in the recommended textbooks and in scientific literature and will be able to use them to continue their studies independently. This will help them recall the topics covered even in the future, even when their memory of the concepts taught in class has faded. The textbooks will remain a point of reference for the student, who will know where to go to revisit in detail the concepts acquired in the past, some of which have inevitably been forgotten.
teacher profile teaching materials
5.000 / 5.000
1. Introduction to Medicinal Chemistry
Definitions: Drug and medicinal product. History. Fields of medicinal chemistry and the role of the medicinal chemist in the modern drug discovery and development process. Origin of drugs: natural drugs, semi-synthetic drugs, synthetic drugs, biotechnological drugs (outline), cell therapies (outline).
2. Essential notions of organic chemistry and biochemistry preparatory to medicinal chemistry
Organic chemistry and biochemistry for medicinal chemistry: recognition of functional groups, amino acids, nitrogenous bases, sugars, mixed structures from 2D and 3D structures, representation of organic molecules in 1D, 2D, and 3D. Proteomics and Genomics in Drug Discovery. Structure of Protein and Nucleic Macromolecules (tertiary structure of DNA and structure and functions of RNA).
3. Pharmaceutical Phase and Pharmacokinetics
Definitions. Pharmacokinetics: Routes of Drug Administration (Enteral, Rectal, Parenteral, Topical), Drug Absorption (Chemical Factors, Biological Factors). Absorption by Passive Diffusion and Oral Route (Lipinski's Rule). Drug Distribution. Bioavailability. Plasma Protein Binding. Drug Metabolism: First-Pass Metabolism, Phase I Metabolism (Structure and Reactions of Cytochrome P450, Oxidative Cycle, Oxidative Reactions Catalyzed by Other Enzymes, Reduction Reactions, Hydrolysis Reactions, Metabolic Activation), Phase II Metabolism (Conjugation Reactions, Conjugation Cofactors, Glucuronidation, Sulfoconjugation, Glutathione Conjugation, Methylation and Acetylation, Dopamine Metabolism, Hippurate Conjugation). Example of Phase I and II Metabolism: Aspirin, Metabolic Stability, Hard and Soft Drugs, Metabolism of the Antiviral Agent Indinavir. Drug Elimination.
4. Pharmacodynamic Phase
Drug/Macromolecule Interactions, Types of Interactions, Covalent Bonds, Ionic Bonds, Ion-Dipole and Dipole-Dipole Interactions, Hydrogen Bonds, Charge-Transfer Complexes, Hydrophobic Interactions, Cation-Pi Interactions, Halogen Bonding, Van der Waals or London Forces, Nonbonding Interactions, Numerical Determination of Interactions. Enzymes as Drug Targets (Types of Inhibitors, Enzyme Kinetics). Receptors (classification, orphan receptors, design of agonist ligands, antagonists, partial agonists, and inverse agonists, desensitization and sensitization, tolerance and dependence, receptor types and subtypes, affinity, efficacy, and potency). Nucleic acids as drug targets. Other drug targets.
3. Drug Discovery and Development
Identification of prototype (hit), hit-to-lead, and lead compounds. Optimization of target interactions. Structure-activity relationships (SAR). Identification of a pharmacophore. Strategies adopted in drug design (substituent variation, structure extension, linear and cyclic homology, variation of the nature of cycles, cycle fusion, isosteres and bioisosteres, structural simplifications, structure rigidification, drug design based on the structure of the interaction site and molecular modeling, multitarget drugs).
4. Antibacterials/Antibiotics
The bacterial cell. Classification by mechanism of action. Metabolite synthesis inhibitors. Folate synthesis inhibitors. Sulfonamides: Origin, mechanism of action, structure-activity relationships, pharmacokinetics, applications. Prontosil, metabolism of prontosil. Trimethoprim: structure, mechanism of action, and association with sulfonamides. Inhibitors of bacterial cell wall biosynthesis. Penicillins: origin, mechanism of action, resistance, methods of preparation of penicillins: 6-APA. [S], structure-activity relationships, structural analogues of penicillin. Benzylpenicillin (G). Phenoxymethylpenicillin (V). Acid sensitivity. Acid-fast penicillins. Beta-Lactamase-Resistant Penicillins (Methicillin, Nafcillin, Temocillin, Oxacillin, Cloxacillin, Flucloxacillin, Dicloxacillin). Broad-Spectrum Penicillins (Penicillin N, Penicillin T, Ampicillin, Amoxicillin, Pivampicillin, Talampipicillin, Bacampicillin). Penicillin Prodrugs. Carboxypenicillins (Carbenicillin, Carfecillin, Indanylcarbenicillin, Ticarcillin). Ureidopenicillins (Azlocillin, Mezlocillin, Piperacillin). Clinical Aspects. Cephalosporins: History and Overview. Properties of Cephalosporin C and SAR. Methods for the Preparation of 7-ACA [S] for the Synthesis of Cephalosporins. First Generation Cephalosporins (Cephalothin, Cephaloridine, Cefalexin [Synthesis of 3-Methylated Cephalosporins], Cefazolin), Second Generation Cephamycin C, Cefoxitime and Oximinocephalosporins [Cefuroxime], Ceftazidime), Third Generation Cephalosporins (Cefotaxime, Ceftizoxime, Ceftriazone), Fourth Generation Cephalosporins (Cefepime, Cefpirome), Fifth Generation Cephalosporins (Cefamicin C, Cefoxitime and Oximinocephalosporins [Cefuroxime], Ceftazidime),
Medicinal Chemistry (G.L. Patrick)
Foye's Principles of Medicinal Chemistry
Medicinal Chemistry (A. Gasco, F. Gualtieri, C. Melchiorre)
Programme
5.000 / 5.000
1. Introduction to Medicinal Chemistry
Definitions: Drug and medicinal product. History. Fields of medicinal chemistry and the role of the medicinal chemist in the modern drug discovery and development process. Origin of drugs: natural drugs, semi-synthetic drugs, synthetic drugs, biotechnological drugs (outline), cell therapies (outline).
2. Essential notions of organic chemistry and biochemistry preparatory to medicinal chemistry
Organic chemistry and biochemistry for medicinal chemistry: recognition of functional groups, amino acids, nitrogenous bases, sugars, mixed structures from 2D and 3D structures, representation of organic molecules in 1D, 2D, and 3D. Proteomics and Genomics in Drug Discovery. Structure of Protein and Nucleic Macromolecules (tertiary structure of DNA and structure and functions of RNA).
3. Pharmaceutical Phase and Pharmacokinetics
Definitions. Pharmacokinetics: Routes of Drug Administration (Enteral, Rectal, Parenteral, Topical), Drug Absorption (Chemical Factors, Biological Factors). Absorption by Passive Diffusion and Oral Route (Lipinski's Rule). Drug Distribution. Bioavailability. Plasma Protein Binding. Drug Metabolism: First-Pass Metabolism, Phase I Metabolism (Structure and Reactions of Cytochrome P450, Oxidative Cycle, Oxidative Reactions Catalyzed by Other Enzymes, Reduction Reactions, Hydrolysis Reactions, Metabolic Activation), Phase II Metabolism (Conjugation Reactions, Conjugation Cofactors, Glucuronidation, Sulfoconjugation, Glutathione Conjugation, Methylation and Acetylation, Dopamine Metabolism, Hippurate Conjugation). Example of Phase I and II Metabolism: Aspirin, Metabolic Stability, Hard and Soft Drugs, Metabolism of the Antiviral Agent Indinavir. Drug Elimination.
4. Pharmacodynamic Phase
Drug/Macromolecule Interactions, Types of Interactions, Covalent Bonds, Ionic Bonds, Ion-Dipole and Dipole-Dipole Interactions, Hydrogen Bonds, Charge-Transfer Complexes, Hydrophobic Interactions, Cation-Pi Interactions, Halogen Bonding, Van der Waals or London Forces, Nonbonding Interactions, Numerical Determination of Interactions. Enzymes as Drug Targets (Types of Inhibitors, Enzyme Kinetics). Receptors (classification, orphan receptors, design of agonist ligands, antagonists, partial agonists, and inverse agonists, desensitization and sensitization, tolerance and dependence, receptor types and subtypes, affinity, efficacy, and potency). Nucleic acids as drug targets. Other drug targets.
3. Drug Discovery and Development
Identification of prototype (hit), hit-to-lead, and lead compounds. Optimization of target interactions. Structure-activity relationships (SAR). Identification of a pharmacophore. Strategies adopted in drug design (substituent variation, structure extension, linear and cyclic homology, variation of the nature of cycles, cycle fusion, isosteres and bioisosteres, structural simplifications, structure rigidification, drug design based on the structure of the interaction site and molecular modeling, multitarget drugs).
4. Antibacterials/Antibiotics
The bacterial cell. Classification by mechanism of action. Metabolite synthesis inhibitors. Folate synthesis inhibitors. Sulfonamides: Origin, mechanism of action, structure-activity relationships, pharmacokinetics, applications. Prontosil, metabolism of prontosil. Trimethoprim: structure, mechanism of action, and association with sulfonamides. Inhibitors of bacterial cell wall biosynthesis. Penicillins: origin, mechanism of action, resistance, methods of preparation of penicillins: 6-APA. [S], structure-activity relationships, structural analogues of penicillin. Benzylpenicillin (G). Phenoxymethylpenicillin (V). Acid sensitivity. Acid-fast penicillins. Beta-Lactamase-Resistant Penicillins (Methicillin, Nafcillin, Temocillin, Oxacillin, Cloxacillin, Flucloxacillin, Dicloxacillin). Broad-Spectrum Penicillins (Penicillin N, Penicillin T, Ampicillin, Amoxicillin, Pivampicillin, Talampipicillin, Bacampicillin). Penicillin Prodrugs. Carboxypenicillins (Carbenicillin, Carfecillin, Indanylcarbenicillin, Ticarcillin). Ureidopenicillins (Azlocillin, Mezlocillin, Piperacillin). Clinical Aspects. Cephalosporins: History and Overview. Properties of Cephalosporin C and SAR. Methods for the Preparation of 7-ACA [S] for the Synthesis of Cephalosporins. First Generation Cephalosporins (Cephalothin, Cephaloridine, Cefalexin [Synthesis of 3-Methylated Cephalosporins], Cefazolin), Second Generation Cephamycin C, Cefoxitime and Oximinocephalosporins [Cefuroxime], Ceftazidime), Third Generation Cephalosporins (Cefotaxime, Ceftizoxime, Ceftriazone), Fourth Generation Cephalosporins (Cefepime, Cefpirome), Fifth Generation Cephalosporins (Cefamicin C, Cefoxitime and Oximinocephalosporins [Cefuroxime], Ceftazidime),
Core Documentation
Medicinal Chemistry (G. Costantino, G. Sbardella)Medicinal Chemistry (G.L. Patrick)
Foye's Principles of Medicinal Chemistry
Medicinal Chemistry (A. Gasco, F. Gualtieri, C. Melchiorre)
Attendance
Attendance at the course lectures is mandatory.Type of evaluation
The assessment method of the course is characterized by five possible oral exam appeals. The teacher offers full willingness to organize any postponement for each appeal in order to meet the requests of the students. This is to give the students the widest possibilities to optimize the outcome of the exam. During the oral examination the teacher verifies the knowledge and learning that the student has acquired on all parts of the exam program. The topics presented should be treated with a language appropriate to a professional operating in the world of pharmacy. The elements taken into consideration for the evaluation are: the knowledge of the subject in all the parts described in the program, the use of an appropriate scientific language, the active participation during the lectures and the laboratory exercises, the ability of reasoning demonstrated in the examination interview, the ability to study autonomously on the suggested texts. Sufficient knowledge of the topics covered, in the various parts of the program, is required for passing the exam with minimum grades. To achieve a score of 30/30 cum laude instead, the student must demonstrate that he has acquired excellent knowledge of all the topics covered during the course, being able to connect them in a logical and consistent way. He/she has also to demonstrate that it has mastered the subject, moving through it with security, appropriateness and naturalness.