PHARMACEUTICAL AND TOXICOLOGICAL CHEMISTRY I
Learning outcomes of the course unit
The course provides general principles of medicinal chemistry, evidencing the relationships between drug structure and their therapeutically relevant properties. Analyse the classification, the chemical, physicochemical and biological properties, the mechanism of action, structure-activity relationships and synthesis of main atiinfective and antitumor drugs.
Specific objectives, following Dublin Descriptors, are:
1. Knowledge and understanding: for drug classes object of the course, it is required to know: names, formulas (for simpler compounds), source, use; to recognize complex formulas and understand SAR, chamical, physicochemical, toxicological and metabolic properties, synthesis.
2. Applying knowledge and understanding: for drugs explicitely treated and for similar ones, it is required to be able to: assign a name given a formula and vice versa; to predict chemical and physicochemical properties of drugs and discuss their possible impact on biological properties, including metabolism and toxicity; to propose and discuss possible routes for drug synthesis or production.
3. Making judgements: it is required to procuce proper comments about SARs, metabolism and related toxicity, drug production, chemical and metabolic drug-drug intearaction.
4. Communication skills: it is required to illustrate, also with an original approach, an issue presented during the lessons and to properly answer to questions, rebut criticisms and apply suggestions.
5. Learning skills: the student is expected to learn how to infer general rules (structure-activity and structure-property relationships) from actual cases (drugs), which can be classified following different criteria.; how to manage dynamically his own wealth of knowledge about drug chemistry and classification; how to search and critically assess information on drug structure and properties.
The exams of Organic Chemistry II and General Physiology must be passed before the examination.
Course contents summary
In the first part, general themes will be addressed, including drug nomenclature, principles of pharmacokinetics, metabolism and mechanism of action, as well as basics on structure-activity relationships. The second part will be focused on the primcipal classes of antibacterials, antiprotozoan, antifungal, antihelmintic, antiviral and antitumor drugs.
1 - General subjects
1.1 - Priniciples of medicinal chemistry. Phases of drug action: pharmaceutics, pharmacokinetics, pharmacodynamics. Drud distrinution. Drug metabolism. Prodrugs. Drug mechanism of activity: receptors; enzymes and their inhibitors; other targets. Physicochemical and chemical properties of drugs. 1.2 - Structure and biological activity. Specific and non-specific MoAs. Optical7geometrical isomerism and biological activity; conformations and biological activity. Isosterism and bioisosterism; privileged structures and pharmacophores. QSAR.
2 - Specific subjects. Antibiotics: beta-lactams; macrolides; aminoglycosides; tetracyclines; ansamycines; polipeptides; other antibiotics. Synthetic antibacterials: sulfa drugs, nitroheterocycles, quinolonices, oxazolidinones. Antimycobatterial drugs. Antifungals: polyene antibiotics, griseofulvin, tiocarbamates, allilamines, flucitosin, azoles, caspofungines. Antiprotozoal drugs. Antielmintics. Antivirals. Antitumor drugs: alkylating agents; DNA-complexing agents and topoisomerase inhibitors; antimetabolites; antimitotics; TK inhibitors; other antitumor drugs.
Williams-Lemke: "Foye's Principi di Chimica Farmaceutica", PICCIN, Padova.
G.L. PATRICK: Introduzione alla chimica farmaceutica; Edises Napoli.
Oral lesson with slide projection. General and specific
themes will be discussed, delivering the essential information and showing, also stimulating interactions with students how to build knowledge that can be transferred over different drug classes, e.g. on prediction of physico-chemical properties from drug formulas, on the identification of pharmacophore elements and of chemical functions that may undergo metabolic toxification.
Assessment methods and criteria
The student achievements will be evaluated by oral examination. Questions from the eaxminator and discussion will aim at establishing if the objectives of knowledge and comprehension have been achieved and if the studen is able to explain clearly and correctly the subjects. Through specific questions, the ability to apply student's knowledge to problems regarding medicinal, farmaceutical or toxicological chemistry for drug classes will be assessed.