OVERVIEW

The course is developed with theoretical and practical lessons. The main topics of the course are focused on molecular modeling and bioinformatic tools to guide the design of compounds as multi-target agents and to evaluate repositioning strategies towards different therapeutic applications of drugs.

AIMS AND CONTENT

LEARNING OUTCOMES

The course aims to provide a basic understanding about the medicinal chemistry, molecular modeling and bioinformatic strategies, guiding the design of multi-target bioactive compounds. Theoretical and experimental lessons will be developed, via in silico simulations. Exploring case studies and drug repositioning approaches will allow to improve knowledge-based abilities in multi-drug repurposing and optimization.

AIMS AND LEARNING OUTCOMES

The course aims to provide the basic concepts of pharmaceutical chemistry to explore the structure-activity relationships of bioactive compounds towards various pharmacological targets, in order to obtain multi-target compounds, via molecular modeling methods. Furthermore, this aims to provide information to optimize drug-receptor interactions and drug candidates pharmacokinetics properties, using bioinformatics approaches. It will also address Study of drugs and proteins will be explored to guide approaches for drug repositioning.

At the end of the course, the student will be able to create databases for the analysis of ligands and bioactive compounds, manipulate and study in 3D the characteristics of proteins as drug targets, and perform structural similarity analysis with other homologous proteins.

The student will be able to propose repositioning analyses of bioactive compounds, and to improve their pharmacokinetic profile. The student will be able to analyze variously promising compounds with multi-target action, performing molecular docking simulations and quantitative structure-activity correlations, being able to propose structural variations useful for their optimization. The student will be able to describe and explain case studies of drug repositioning strategies and of multi-target compounds design, with applications in various therapeutic areas.

PREREQUISITES

Not required

TEACHING METHODS

The course is developed with theoretical and practical lessons. Free online platforms and informatic tools will be exploited to analyze in silico proteins and drug-like compounds. Practical simulations will be performed along the course and individually out of the lessons. The results will be discussed at the end of the course and during examination.

SYLLABUS/CONTENT

Theoretical topics

• Rational design of hit compounds, in medicinal chemistry
• Computational methods to analyze macromolecules and ligands in silico
• Three-dimensional analysis and comparison of proteins: probing the putative drug binding pockets
• Homology modeling and molecular docking techniques.
• Molecular modeling and bioinformatic methods to optimize ligand-protein interactions.
• Free software and platforms to design new compounds analogues
• Design of multi-target compounds: case studies
• Molecular modeling methods to evaluate the bioavailability, metabolism and safety profile of drugs.
• Drugs repositioning: case studies

Practical exercises via computer simulations

• Free platforms and software to display proteins and ligands
• Free platforms to analyse proteins and ligands, to guide the design of novel analogues.

RECOMMENDED READING/BIBLIOGRAPHY

Manuale di Chimica Farmaceutica- Progettazione, meccanismo d’azione e metabolismo dei farmaci, Richard B. Silverman, Mark W. Holladay - EDRA

Principi di Chimica Farmaceutica, Thomas L. Lemke, S. William Zito, Victoria F. Roche, David A. Williams - PICCIN

TEACHERS AND EXAM BOARD

LESSONS

LESSONS START

First semester. The teaching schedule will be published as soon as it is available.

Class schedule

The timetable for this course is available here: Portale EasyAcademy

EXAMS

EXAM DESCRIPTION

The exam consists of an oral test where the approaches used in the practical exercises and the main contents of the teaching will be discussed.

ASSESSMENT METHODS

The examination includes an oral test and an evaluation of the student acquired ownership in terms of classical pharmaceutical chemistry approaches, molecular modeling, and bioinformatics in designing multi-target drugs or applying repositioning strategies. Presenting the activities carried out in the form of practical simulations will allow for the assessment of the level of understanding of the proposed case studies and the ability in proposing the aforementioned multi-target/repositioning methods, for specific examples of proteins and/or compounds series.