The course introduces the concepts and experimental approaches to the chemistry of bioactive substances by consolidating the principles gained under the organic chemistry course, focusing on biogenesis, synthesis, chemical structure and pharmacological properties of bioactive substances . In the first part of the course, the concept of the "pharmacophore theory" will be introduced as a minimal structural unit characterized by a specific biological and clinical activity. Bioactive substances, both of synthetic and natural origin, will be classified according to their main pharmacophores. The student will learn to recognize the pharmacophore even in the context of complex molecular structures. In the second part of the course, critical tools will be provided to associate certain pharmacophorees to specific pharmaceutical and pharmacological applications, with particular attention to the molecular action mechanism by with which the bioactive substances act in the body. The student will be able to understand the natural origin of bioactive organic substances and their possible industrial applications by receiving specific training on the design, development and evaluation of new drugs. In addition, due to the knowledge of molecular action mechanisms, the student may associate the use of bioactive substances with specific nutraceutical, cosmeceutic and cosmetic products, including restrictions on the use of potentially toxic substances and the possibility of their use after functional and structural improvement. This knowledge will enable the student to deal with a professional career within the pharmaceutical, nutraceutical and cosmeceutical industry.
B) EXPECTED LEARNING RESULTS • Knowledge and understanding: Knowledge of the principles that define the minimum structural unit of an organic, natural or synthetic molecule, to have a certain biological activity (pharmacophore theory). Knowledge of the relationship between the type of pharmacophore present in an organic molecule and the pharmaceutical and pharmacological activity. Knowledge ot the molecular-level of the action mechanism of the major families of bioactive substances, with particular attention to substances with antioxidant, antiviral, anti-inflammatory and antitumour activity. Knowledge of the key steps for the design of a drug, and procedures for its clinical validation and use. Knowledge of the origin and distribution in nature of the main families of biologically active natural organic substances. • Applied knowledge and understanding: In addition to the knowledge gained through the bioactive substance chemistry study, students will be able to apply theoretical concepts acquired during the course in solving practical exercises based on the teacher's request to present possible schemes for the design of a drug, having the initial indication of the target of action at the molecular level and knowing the type of pathology against which the treatment therapy is to be developed. In this case, students will also have to apply their previous knowledge of chemistry and biology for complete resolution of the problem. • Making judgements: At the end of the course, the student will have acquired the necessary training for full autonomy of judgment on the possibility of using a certain organic substance of natural or synthetic origin for the therapy of a certain pathology . The student will then be able to link the acquired knowledge of biochemistry, molecular biology, enzymology, physiology and genetic to the design of a substance applicable in the pharmaceutical, nutraceutical and cosmeceutical fields. • Communication skills: students will be continuously and consistently invited to participate actively in the lesson in order to deepen the topic and to collect proposals for possible solutions in the case of complex phatological scenarios. In this activity, students will be called upon to meet in order to support their ideas. The educational pitch is aimed at increasing the communicative skills and the ability to know how to work and to confront a group, all aimed at consolidating the acquired concepts. • Learning Skills: Students' learning abilities will be evaluated during the course of the course by tests that will allow to individually monitor the maturation state of the knowledge, highlighting the student's ability to return the aquired cencepts.
Importance and function of secondary metabolism in animal and plant cells. General examples. The role of secondary metabolites in pharmaceutical, nutraceutical, cosmetic and cosmoceutical applications. Evaluation of structure-activity relationships of natural organic substances through applications of computational chemistry.
Terpenes and terpenoids Diffusion in nature and biological and pharmacological properties. 3 (R) -Mevalonic acid route. Rule of isoprene. Regular terpenes and irregular terpenes. Bioinformatics applications for the recognition of terpene structures. Classification of terpenes. Biosynthesis of 3 (R) -mevalonic acid, isopentenyl pyrophosphate and dimethylallylpyrophosphate. Hemiterpenes. Acyclic monoterpenes (geraniol, linalool, nerol) and cyclic monoterpenes (limonene, terpineol, camphor). Iridoids and sec-iridoids. Sesquiterpenes (artemisinin and antimalarials). Triterpenes and steroids (corticosteroids, androgens, estrogens and progestogens). Phytosteroids. Tetraterpenes (carotenoids, apocarotenoids and xanthophylls). Vitamin A and molecular mechanism of vision. Antioxidant activity of carotenoids, protection mechanism from lipid peroxidation.
Phenols and polyphenols Pharmacophore theory. The phenolic and polyphenolic pharmacophore. The scichimic acid route and the polyketide route (malonic acid route). Antioxidant capacity of phenols and polyphenols, structure / activity relationship. Computational evaluation of the efficacy of the phenolic and polyphenolic pharmacophore. Pro-oxidant capacity of phenols. Biosynthesis of scichimic acid. Gallic acid, gallotannins and elagiotannins, nutraceutical and pharmaceutical applications. Salicylic acid and salicin, antipyretic and anti-inflammatory properties. Biosynthesis of aromatic alpha-amino acids (phenyl alanine and tyrosine). Biosynthesis of phenylpropanoid acids. Coumarins. Anticoagulant activity of coumarins, mechanism of action of dicumarol and warfarin. Lignans and Neolignans. Antitumor activity of lignans, the case of podophyllotoxin and etoposide. Lignin, chemical structure, chemical-physical properties and bionanotechnological applications. Use of lignin nanoparticles in cosmetics and cosmeceutics. Applications in materials science and in the production of bioplastics. Production of bio-inks, biocatalysts and biosensors in the clinical and environmental fields. Melanin and catecholamines. Computational calculation methods for the determination of the redox properties of melanins. Role of catecholamines in the central nervous system and in the treatment of neurodegenerative diseases. Stilbenes and chalcons. Nutraceutical uses. Flavonoids. Classification and biosynthesis. Antioxidant, cardioprotective, antimicrobial and antitumor activity. Industrial uses.
Alkaloids Diffusion in nature and biological and pharmacological properties. Classification and description of the main biosynthetic pathways of piperidine, tropane, quinoline, isoquinoline, morphinane, and indole alkaloids. Presence in nature of alkaloids and main applications in the pharmaceutical field. Design of active analogues of alkaloids through the use of bioinformatics techniques.