Ateneo - UPO

The integrated course addresses, through a multidisciplinary approach, the production, characterization and design of bioactive molecules of pharmaceutical interest. The Medicinal Chemistry and Molecular Modeling Laboratory module considers drugs as chemical objects, examining how molecular structure determines their properties, target recognition and metabolic fate, and which structural modifications can be introduced to improve their profile; these concepts are also applied through molecular modeling activities. The Phytochemistry and Pharmaceutical Biotechnology Applied to Medicinal Plants module addresses traditional and innovative strategies for the production of secondary metabolites of pharmaceutical interest, with particular emphasis on in vitro plant cultures, cell and tissue cultures, micropropagation, genetic transformation and the biotechnological production of active compounds. Overall, the course connects the origin and production of bioactive molecules with the understanding of their properties and the strategies used for their development in the pharmaceutical field.

Medicinal Chemistry and Molecular Modeling Laboratory module

Recommended textbooks, one to be chosen as the main reference:
A. Gasco, F. Gualtieri, C. Melchiorre, Chimica farmaceutica, second edition, 2020. ISBN 978-8808420268.
W. O. Foye, T. L. Lemke, S. W. Zito, V. F. Roche et al., Principi di chimica farmaceutica, seventh edition, 2021. ISBN 978-8829931538.
G. Patrick, An Introduction to Medicinal Chemistry, seventh edition, 2023. ISBN 978-0198866664.
G. Costantino, G. Sbardella, Chimica Farmaceutica, first edition, 2024. ISBN 978-8836231522.

Phytochemistry and Pharmaceutical Biotechnology Applied to Medicinal Plants module
W. Schwab, B. Markus, M. Lange, M. Wüst (eds.), Biotechnology of Natural Products.
D. J. A. Crommelin, R. D. Sindelar, B. Meibohm, Pharmaceutical Biotechnology.

Open-access scientific publications indicated in the teaching material of the module.

Both modules also use teaching materials prepared by the lecturers and made available through the D.I.R. platform, including lecture slides, exercises, operating guides, working files and articles from the primary scientific literature.

For examination preparation, students should refer to the materials specifically indicated in the syllabi of the individual modules.

The integrated course contributes to the educational objectives of the Degree in Biotechnology, chemical-pharmaceutical curriculum, by providing a multidisciplinary view of the pathway leading from the production and identification of a bioactive substance to the understanding of its molecular properties and its potential development as a product of pharmaceutical interest.

The integration of medicinal chemistry, molecular modeling, phytochemistry and plant biotechnology allows bioactive molecules to be approached both from the standpoint of their origin and production and from that of the relationships between structure, properties, biological activity and metabolic fate.

At the end of the integrated course students are able to:

describe and relate the main medicinal chemistry and biotechnological strategies used to obtain, characterize and develop bioactive substances of pharmaceutical interest;

relate the behaviour of a pharmaceutically relevant molecule to its structural features, considering physicochemical properties, target recognition, structure-activity relationships and metabolic transformations;

describe and compare the main traditional and innovative strategies used in plant biotechnology for the production of secondary metabolites, identifying their advantages, limitations and fields of application;

apply rational criteria to the assessment and optimization of bioactive molecules, using experimental data, information retrieved from databases and basic computational tools;

critically assess data, methods and strategies used in the different areas covered by the course, recognizing their limitations, potential and implications in the pharmaceutical, food and industrial fields;

use appropriate scientific terminology and clearly and logically communicate the results of an analysis or the characteristics of a chemical or biotechnological process.

In order to follow the integrated course profitably, students should have basic knowledge acquired during the first two years of the Degree programme, particularly in:

general chemistry: acid-base equilibria, pH and pKa, intermolecular interactions and basic thermodynamics;

organic chemistry: main functional groups and their reactivity, acidity and basicity of organic compounds, stereochemistry and the main reaction mechanisms;

biochemistry and molecular biology: structure and function of the main biomolecules, principles of enzyme catalysis and cell organization;

biology: basic organization and functioning of cells and plant organisms.

No previous molecular modeling skills are required beyond ordinary use of a personal computer; the computational tools are introduced within the relevant module.

The integrated course uses complementary teaching methods reflecting the different nature of the two modules.

In the Medicinal Chemistry and Molecular Modeling Laboratory module, lectures are integrated with guided exercises, discussion of real molecules and case studies, and practical activities in a computer room. Laboratory activities use chemical and structural databases and basic computational tools to apply medicinal chemistry concepts to real series of compounds.

In the Phytochemistry and Pharmaceutical Biotechnology Applied to Medicinal Plants module, lectures are supported by slides, botanical materials and applied examples concerning the production of secondary metabolites and the main technologies used in plant biotechnology.

The use of case studies and real examples in both modules is intended to develop the ability to apply knowledge, compare alternative strategies and critically assess their advantages and limitations.

Teaching materials are made available through the D.I.R. platform according to the arrangements specified in the syllabi of the individual modules.

MS1851 - Drug Design is an integrated course consisting of the following modules:

MS1852 - Medicinal Chemistry and Molecular Modeling Laboratory;

MS1854 - Phytochemistry and Pharmaceutical Biotechnology Applied to Medicinal Plants.

Assessment of the integrated course is single and collegial. Assessment elements collected within the individual modules are jointly considered by the examination board and the final mark is not obtained by simply averaging separate module marks.

Further information and teaching materials are available on the D.I.R. pages of the individual modules.

Students with physical disabilities, Learning Disabilities or Special Education Needs may request specific services and tools through the relevant University Student Services. After contacting the University service, students may contact the lecturers regarding teaching aspects and the appropriate implementation of examination arrangements.

Assessment of the integrated course MS1851 is single and the final mark is awarded collegially by the examination board, jointly considering the assessment elements collected within the two modules. The final mark is not obtained by averaging separately awarded module marks.

Module MS1852 - Medicinal Chemistry and Molecular Modeling Laboratory

Assessment consists of:

a 45-minute computer-based test consisting of 30 multiple-choice questions, assessing knowledge and the ability to apply medicinal chemistry concepts to molecular structures, including molecules not discussed during the lectures;

an individual 3-5 page laboratory report on the assigned case, followed by a short oral discussion, assessing the use of computational tools, the ability to evaluate the quality and limitations of data and methods, making judgements and communication skills.

Module MS1854 - Phytochemistry and Pharmaceutical Biotechnology Applied to Medicinal Plants

Assessment consists of an oral examination based on open questions covering the contents of the module. The examination assesses knowledge of the main biotechnological processes applied to plants and cell cultures, the ability to identify appropriate approaches for the production of secondary metabolites, the ability to discuss their advantages and disadvantages, and the use of appropriate scientific terminology.

The overall assessment considers the correctness and completeness of knowledge, the ability to apply it to problems and case studies, independent judgement, the ability to connect contents from the two modules and clarity of communication.

The minimum pass level requires correct knowledge of the fundamental concepts of both modules and the ability to apply them to straightforward cases using appropriate scientific terminology. Higher achievement levels require the ability to independently integrate different contents, critically discuss the advantages and limitations of methods and strategies, and formulate justified interpretations or proposals.

The integrated course consists of two complementary modules.

MODULE MS1852 - MEDICINAL CHEMISTRY AND MOLECULAR MODELING LABORATORY

The drug as a chemical object. Role of medicinal chemistry in the drug research and development process. Functional groups, acidic and basic centres, stereochemistry and structural features of pharmaceutically relevant molecules.

Physicochemical properties and drug-likeness. pKa and ionization state, lipophilicity, solubility, polar surface area, hydrogen-bond donors and acceptors, molecular flexibility. Main empirical drug-likeness rules and their limitations.

Molecular recognition and biological targets. Intermolecular interactions, hydrophobic effect, role of water, enthalpic and entropic contributions and stereochemistry of molecular recognition. Chemical features of binding sites and molecular basis of selectivity.

Structure-activity relationships and drug design. Building and interpreting structure-activity series, pharmacophores, isosterism and bioisosterism, main structural modification strategies and multiparameter optimization.

Drug metabolism. Main phase I and phase II transformations, identification of metabolic soft spots, structural strategies for modulating metabolic stability, reactive metabolites and prodrugs.

Identification and optimization of active compounds. Screening, fragment-based approaches, drug repurposing, natural products as starting scaffolds and the hit-to-candidate pathway.

New therapeutic modalities. Introduction to peptides and peptidomimetics, antibody-drug conjugates, degraders, molecular glues and therapeutic oligonucleotides.

Molecular modeling laboratory. Digital representation of chemical structures; SMILES, SMARTS and InChI; searching chemical and structural databases; building and curating structure-activity series; calculation of molecular descriptors and ADMET predictions; conformational analysis; three-dimensional pharmacophores; analysis of protein structures and ligand-protein complexes; guided docking and critical assessment of results.

MODULE MS1854 - PHYTOCHEMISTRY AND PHARMACEUTICAL BIOTECHNOLOGY APPLIED TO MEDICINAL PLANTS

Introduction to plant biotechnology. Definition, history and development. Issues associated with the availability and production of secondary metabolites of pharmaceutical interest.

Traditional approaches. Selection, hybridization, breeding, domestication and propagation for the improvement of medicinal plant crops.

In vitro plant cultures. Plant cell, tissue and organ cultures, micropropagation and the main related techniques.

Genetic transformation and specialized cultures. Genetic engineering, recombinant DNA technology, transgenic plants and organisms, hairy roots and germplasm cryopreservation.

Cell cultures. Stationary liquid cultures, temporary and permanent immersion systems; batch, continuous, semi-continuous and immobilized-cell cultures.

In vitro production of secondary metabolites. Production strategies, selection of highly productive cell lines, advantages and disadvantages compared with conventional sources. Examples of production of active compounds and substances of pharmaceutical and pharmaceutical-technological interest.

Genetically modified organisms. General principles of European and national legislation concerning environmental release, food and feed, traceability, labelling and transboundary movements. Precautionary principle and applied examples.

Case studies are used throughout the two modules to highlight the relationships between the characteristics of bioactive molecules, the way in which they are obtained, and the strategies through which they may be characterized and developed for pharmaceutical applications.

Knowledge and understanding.
Students know the fundamental principles of medicinal chemistry and plant biotechnology applied to bioactive substances. They understand the relationships between molecular structure, physicochemical properties, target recognition and metabolism; the main strategies for structural modification and optimization; the principles and applications of in vitro cell, tissue and plant cultures; and the main strategies for genetic transformation and the biotechnological production of secondary metabolites.

Applying knowledge and understanding.
Students are able to analyse a pharmaceutically relevant molecule by identifying its relevant structural features, predict selected properties and propose justified modifications; use information retrieved from databases and basic computational tools; and identify and describe the most appropriate biotechnological approach for different objectives involving the production or improvement of secondary metabolites.

Making judgements.
Students are able to critically compare alternative methods and strategies, assess the quality and comparability of experimental or database-derived data, recognize the main limitations of computational predictions, and discuss the advantages and disadvantages of different technologies used for the production of bioactive substances.

Communication skills.
Students are able to describe molecules, processes and strategies using appropriate scientific terminology; present results, interpretations and limitations of an analysis in written and oral form; and justify the choice of a chemical, computational or biotechnological strategy.

Learning skills.
Students are able to use textbooks, scientific literature, databases and technical documentation to independently investigate a medicinal chemistry or biotechnology problem and transfer acquired knowledge to cases not directly covered during the lectures.

Minimum pass level.
Correctly recognizing and describing the fundamental concepts of both modules; identifying the main relationships between molecular structure, properties and activity; describing the main plant biotechnology techniques and their applications; and using appropriate scientific terminology.

Advanced level.
Independently integrating knowledge from the two modules, critically approaching a case not covered during the lectures, comparing alternative strategies, formulating a justified proposal for a structural modification or biotechnological approach, and discussing its potential and limitations with well-supported arguments.