MEDICINAL AND TOXICOLOGICAL CHEMISTRY 2

Università degli Studi
"G. d'Annunzio"

Chieti - Pescara

Single discipline educational activity

Course Sheet

Course code:

00204

Academic Year of enrolment:

2019

Year of supply:

2022/2023

Type of Course:

Characterising

Degree:

Course of Single Cycle Degree 5 years in MEDICINAL CHEMISTRY AND PHARMACEUTICAL TECHNOLOGY

Disciplinary Sector:

Pharmaceutical Chemistry

Language:

Italian

Location:

CHIETI

Credits:

Programme Year:

Professor and Collaborators:

CACCIATORE Ivana

Cycle:

Second semester

Obligatory attendance:

Yes

Minimum hours of attendance:

Hours of classroom activity:

Individual study hours:

153

Prerequisites:

Medicinal and Toxicological Chemistry I

Organic Chemistry II

Objectives

Prerequisites: students attending the Pharmaceutical and Toxicological Chemistry II course must have a good familiarity with organic compounds and the basic mechanisms of organic chemistry, as well as basic notions of physiology, biology and pharmacology.
Teaching provided: the course provides students with the tools for an analytical and critical approach to the discipline. A particular space is dedicated to the understanding of the phases of drug design and of the molecular optimization approaches of the progenitors. In the second part of the course selected topics of pharmaceutical chemistry are proposed (antimicrobials, pesticides, antitumors, hormones, cardiovascular drugs), whose treatment insists on mechanistic, design and synthetic aspects. Students are provided with information on the chemical and physico-chemical properties of drugs, on their biological effects, on the mechanism of action on a molecular basis, on the relationships between structure and biological activity, on pharmacokinetic properties, on metabolic and toxicological pathways. The subject is characterized in its increasingly interdisciplinary connotations, with the aim of sensitizing the student to the fascinating world of drugs.
Expected results: the student is expected to learn the fundamentals of the action of drugs and their complex interaction with the different biological systems on a stereo-electronic basis. The methodological approach to which he was addressed will allow him to independently develop concepts and strategies, illustrated in class with specific examples, in any area of the discipline. The student will acquire the ability to fine-tune the rational design and synthetic strategy of drugs for new macromolecules identified as targets. The preparation gained enables the students to face a period of internship in a Pharmaceutical Chemistry laboratory.

Contents

INTRODUCTION TO DRUG DESIGN-DISINFECTANTS AND ANTISEPTICS-ANTIMICROBIALS-ANTIPARASITAL AGENTS-ANTICANCER DRUGS-STEROID HORMONES-AUTACOIDS AND NON STEROIDAL ANTIINFALMMATORY DRUGS-PEPTIDE HORMONES-CARDIOVASCULAR AGENTS-DESIGN AND SYNTHESIS OF SIGNIFICANT DRUGS.

Extended Syllabus

1) INTRODUCTION
Principles of drug discovery, design, and development. Pro-drug and bio-precursor design. Pro-Tide drugs. Therapeutic targets: enzymes, receptors, cellular structures.

2) DISINFECTANTS AND ANTISEPTICS
Alcohols and related compounds; phenols and derivatives; oxidizing agents; halogen- containing compounds; cationic surfactants; dyes; mercurials.

3) ANTIMICROBIALS
Antibacterials: sulfonamides and dihydrofolate reductase inhibitors; beta-lactam antibiotics; macrolide antibiotics; lincomycins; tetracyclines; chloramphenicol and analogs; aminoglycoside antibiotics; glycopeptide antibiotics, polypeptide antibiotics; antimicrobial cationic peptides and analogs, fosfomycin; other antibacterial agents: nitrofurans, metronidazole, methenamine, quinolones, oxazolidiones. Antimycobacterials: first- and second-line antitubercolar drugs, novel agents targeting the cell wall biosynthesis, bedaquiline; antileprotic drugs.

4) ANTIPARASITAL DRUGS
Antiprotozoal agents: antimalarials; chemotherapy of toxoplasmosis, amebiasis, giardiasis, trichomoniasis, trypanosomiasis, leishmaniasis, pneumocystosis. Anthelmintics. Antiviral drugs: treatment of HIV, HCV, and HSV infections; anti-influenza agents; tretment of CoViD19. Antifungals: allylamines; griseofulvin; azole compounds; miscellaneous antifungal agents; polyene macrolides; echinochandins.

5) ANTICANCER DRUGS
Alkylating agents; metalating compounds; antimetabolites; Vinca alkaloids, hemiasterlins and analogs (mentions), taxoids and other natural products; actinomycins; anthracyclines; bleomycins; mitomycins; asparaginase. Enzymatic inhibitors of tyrosin kinases and (mentions) histone deacetylases, matrix metalloproteinases, carbonic anhydrases.

6) STEROID HORMONES
Structure, nomenclature, and biosynthesis of steroid hormones; adrenal cortex hormones: glucocorticoids and mineralocorticoids; mineralocorticoid antagonists. Sex hormones: estrogens; antiestrogens; progestins; oral contraceptives; antiprogestins; androgens; antiandrogens; anabolic agents.

7) AUTACOIDS AND NON STEROIDAL ANTI-INFLAMMATORY DRUGS
Eicosanoids: biosynthesis, structure, and biological properties of prostaglandins, prostacyclin, tromboxanes and leukotrienes. Non steroidal anti-inflammatory drugs: salicylates and mefenates; aryl- and heteroaryl-acetic acid derivatives, aryl-propionic acid derivatives; oxicams; pyrazolidine derivatives; acetanilids; COX2 selective inhibitors. Treatment of asthma.

8) PEPTIDE HORMONES
Hormones of the hypothalamus-hypophysis axis and synthetic analogues; hormones of the thyroid gland; uterotonic and tocolytic agents. Pancreatic hormones and drugs acting on glucidic metabolism.

9) CARDIOVASCULAR DRUGS
Antithrombotic agents: anticoagulant, antiplatelet, and fibrinolityc drugs. The renin-angiotensin system: renin inhibitors, ACE inibitors, AT1-antagonists.

10) SYNTHESIS OF SIGNIFICANT DRUGS

11) SELECTED EXAMPLES OF DRUG DESIGN
Pro-Tide pro-drugs; activation of bio-precursors by reductive or oxidative pathways; omapatrilat; pro-drugs of penicillins and cephalosporins; phenylglycil-boronic acids as beta-lactamase inhibitors; cephalosporin-quinolone conjugates; siderophore- cephalosporin conjugates; oxamniquine; ritonavir; cyclophosphamide; glutathione- nitrogen mustard conjugates; estramustine phosphate; sulindac.

Recommended Bibliography

1. Autori vari: Chimica Farmaceutica (II Edizione), a cura di Gasco, A., Gualtieri, F., Melchiorre, C., Casa Editrice Ambrosiana, Rozzano (MI) (2020)
2. Autori vari: Principi di Chimica Farmaceutica (VI Edizione italiana, a cura di Dall’Acqua, F., basata sulla VII edizione americana del Foye’s Principles of Medicinal Chemistry, a cura di Lemke T. L. e Williams D. A.), Piccin Nuova Libraria, Padova (2014)
3. Autori vari: Chimica Farmaceutica (I Edizione italiana, traduzione della XII edizione americana del Wilson & Gisvold’s Textbook of Organic, Medicinal and Pharmaceutical Chemistry, a cura di Beale, J. M., jr. e Block, J. H.) Casa Editrice Ambrosiana, Rozzano (MI) (2014)

Methods of Provision

Conventional

Teaching Methods

Traditional teacher-led lessons

Evaluation methods

Verification of learning:

In itinere tests are foreseen. Verification of learning involves a written test and an oral exam on appeal.
Written test lasting 2 hours with 10 questions.
Minimum mark for admission to the oral exam: 18/30.
Oral exam focuses on an in-depth interview on various topics covered in class.

Contacts/More Information

The frequence to the course is mandatory.

Università degli Studi
"G. d'Annunzio"

Chieti - Pescara

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