AIMS AND CONTENT

LEARNING OUTCOMES

The course deals with specific classes of drugs: antimicrobials, antiprotozoals and antivirals. The principles of antitumor chemotherapy and chemotherapeutic drugs are also covered. Finally, drugs derived from hormones and vitamins are described. The structural and kinetic characteristics and modes of action of each class of compounds are detailed and examples of synthesis of the main drugs are reported, so that the student can have a complete overview of these families of therapeutic agents.

AIMS AND LEARNING OUTCOMES

The focus of the course is to discuss the modes of action, the structure-activity relationships, the pharmacodynamic and pharmacokinetic profiles and the synthetic methodologies of various classes of anti-infective and anti-tumour chemotherapeutic agents currently used in the clinical practice.

At the end of the course the student will master the theoretical knowledge to:

• understand, at the molecular level, the mechanisms of action of the analysed drugs;
• distinguish the structural determinants characterizing the different classes of analysed drugs;
• analyse the structure-activity relationships defined during the development of clinically used antitumor and anti-infective drugs;
• identify the structural determinants responsible for metabolic instability, resistance phenomena and side effects associated to the clinical use of discussed drugs;
• describe and comment on the synthetic methodologies used for the preparation of the described drugs.

TEACHING METHODS

In-person classes for a total of 40 hours.

Any Student with documented Specific Learning Disorders (SLD), or with any special needs, shall reach out to the Lecturer(s) and to the dedicated SLD Representative in the Department ( Prof. Luca Raiteri, Luca.Raiteri@unige.it ) before class begins, in order to liaise and arrange the specific learning methods and ensure proper achievement of the learning aims and outcomes. VERY IMPORTANT: any request for compensatory tools and adaptations in the exam MUST be done within 10 working days before the date of the exam according to the instructions that can be found at https://unige.it/disabilita-dsa/comunicazioni

The slides are available in aulweb website.

SYLLABUS/CONTENT

The pharmacodynamics/pharmacokinetics properties of the different classes of drugs will be discussed highlighting the structure-activity relationships and the synthetic procedures for their preparation. In detail:

1. Antiseptics and disinfectants

2. Sulfonamides

3. Antibiotics

• a. Antibiotics that act on the bacterial membrane: b-lactams (penicillins, cephalosporins, carbapenems, monobactams); vancomycin and teicoplanin; bacitracin; polymyxin B, cycloserine; fosfomycin; daptomycin
• b. Antibiotics that act on protein synthesis: tetracyclines; aminoglycosides; macrolides; streptogramins; lincosamides; amphenicols; cyclopeptides; fusidic acid
• c. Antibiotics that act on transcription: ansamycins, mupirocin and novobiocin

4. Quinolones

5. Nitrofuran compounds

6. Oxazolidinones

7. Antimycobacterial chemotherapeutics

• a) Anti-TB agents (e.g., isoniazid, ethionamide, prothionamide, pyrazinamide, rifamycins, aminoglucosides, quinolones, ethambutol, PAS, cycloserine, thioacetazone, clofazimine, bedaquine).
• b) Anti-leprosy agents (e.g., dapsone and analogues, thalidomide).

8. Antifungal chemotherapeutics: polyenes (amphotericin B), imidazole and triazole azoles. Allyl- and benzylamines. Thiocarbamates. Morpholines. Echinocandins.

9. Antiprotozoal chemotherapeutics

• a) Antimalarials (e.g., quinine, mefloquine, 4-aminoquinolines, 8-aminoquinolines, artemisinins, pyrimethamine/sulfadoxine, proguanil, atovaquone).
• b) Antitrypanosome agents (e.g., nifurtimox, benznidazole, suramin, pentamidine, melarsoprol, eflornithine).
• c) Antileishmanial agents (e.g., antimony salts, miltefosine, paromomycin).
• d) Anti-amoebiasis, giardiasis and trichomoniasis agents (e.g., Metronidazole, tindazole, nitazoxanide)
• e) Anti-toxoplasmosis agents (e.g., spiramycin, pyrimethamine, sulfadiazine, clindamycin)

10. Anthelmintics

• a) Anti-schistosomiasis (e.g., oxamniquine, praziquantel, metrifonate)
• b) Anti-taeniasis (e.g., niclosamide, albendazole)
• c) Anti-ascariasis (e.g., mebendazole, pyramtel, ivermectin)
• d) Anti-lymphatic filariasis (e.g., diethylcarbamazine)
• e) Anti-scabies and pediculosis (e.g., lindane, crotamiton, pyrethrins and pyrethroids)

11. Antivirals

• a) inhibitors of virus recognition and penetration (e.g., amantadine, rimantadine, interferons)
• b) inhibitors of viral genome replication (e.g., aciclovir, cidofovir, famcicovir and pencicovir, gancicovir, foscarnet, idoxuridine, ribavirin, vidarabine)
• c) inhibitors of protein synthesis (e.g., metisazone, fomivirsen, boceprevir, telaprevie)
• d) inhibitors of viral release (e.g., zanamivir, oseltamivir)
• e) anti-HIV agents (reverse transcriptase inhibitors, proteases, integrases, fusion inhibitors)
• f) anti-HCV agents
• g) anti-SARS-CoV2 agents

12. Antitumor agents

• a) Alkylating agents (e.g., nitrogen mustards, non-classical alkylating agents, N-nitrosoureas, busulfan, alretamine, platinum complexes)
• b) Antimetabolites (e.g., pyrimidines: 5-FU, cytarabine; purines: 6-MP, 6-thioguanine; methotrexate)
• c) Antitumor antibiotics (e.g., anthracyclines, bleomycins, actinomycin D, mitomycin)
• d) Antimitotics (e.g., vinca alkaloids, taxanes)
• e) Poisons and topoisomerase inhibitors (e.g., podophyllotoxins, camptothecins)
• f) Protein kinase inhibitors (type I and II inhibitors, monoclonal antibodies)
• g) Proteasome inhibitors (e.g., bortezomib)
• h) HDAC inhibitors (e.g., vorinostat, romidepsin)

13. Peptide hormones

• a) Calcium homeostasis (parathyroid hormone, calcitonin, vitamin D, bisphosphonates, hormone therapy)
• b) Thyroid drugs (T3 and T4, thyrostatics)
• c) Diabetes (insulins, oral hypoglycemics)

14. Steroid hormones

• a) Estrogens (natural oestrogens and their derivatives, semi-synthetic oestrogens, non-steroidal oestrogens, antioestrogens, SERMs, aromatase inhibitors)
• b) Progestins (agonists and d antagonists, oestrogen-progestin combinations)
• c) Androgens (anabolic, SARMs, antiandrogens, 5a-reductase inhibitors)
• d) Corticosteroids (minerals and glucocorticoids)

15. Diagnostic and therapeutic radiopharmaceuticals

RECOMMENDED READING/BIBLIOGRAPHY

Foye's. Principi di chimica farmaceutica. Piccin

Wilson & Gisvold. Chimica Farmaceutica. Casa Editrice Ambrosiana

Gasco, Gualtieri, Melchiorre. Chimica farmaceutica. Casa Editrice Ambrosiana

Costantino, Sbardella. Chimica farmaceutica. Edises

TEACHERS AND EXAM BOARD

LESSONS

LESSONS START

According to academic calendar available at https://corsi.unige.it/corsi/11673/studenti-orario

Class schedule

The timetable for this course is available here: Portale EasyAcademy

EXAMS

EXAM DESCRIPTION

The exam includes an oral interview (in presence, about 45 minutes long) concerning the topics covered during the lessons.

The exam will be considered passed if the student obtains a grade equal to or greater than 18/30.

ASSESSMENT METHODS

The oral exam aims to evaluate the student's preparation in terms of:

• mastery of the topics covered during the lessons;
• clarity of the presentation and use of proper scientific terminology;
• ability to correlate among different compounds of the same therapeutic class.

FURTHER INFORMATION

For further information, please contact the professor.