Chemistry and Disease

The module covers some key aspects of medicinal chemistry and biomedicine to build an advanced, applied chemical/bio-chemical background for modern chemists and biochemists.

It focuses on

(i) molecular aspects of disease
(ii) impact of chemistry in the understanding of disease at the molecular level
(iii) effective development and provision of chemotherapeutic agents for the prevention, control and eradication of disease.

All aspects of chemistry, including organic, inorganic, physical, biological and structural will be included.

Aims include the:

importance of chemical approaches to target disease
molecular bases of key types of diseases
biological action of therapeutics
importance of inorganic chemistry in biomedical applications
modern approaches in design and development of new chemotherapeutics
role of chemistry in health maintenance and disease prevention

Learning objectives

importance of historical achievements of chemistry to modern biomedicine
wide context of interaction of pharmaceuticals with human body
particular and common molecular events behind the main types of diseases and the need of their elucidation for effective chemical interventions
issues in a successful chemical approach to complex diseases: the inter-dependence of key molecular signalling and regulatory pathways in cancer, diabetes, neurodegeneration
role of metals for life processes, therapy and analytical/imaging progress of biomedicine
need for understanding of required properties of drug molecule
the advances in modern drug design process and drug delivery
confidence in tackling biomedical-pharmaceutical problems
building a broad background in medicinal chemistry and biomedicine: preparation for biomedical-research projects, pharma-based industrial placements, and biomedicine-oriented PhDs
understanding of wide and intertwined molecular and chemical contexts in biomedicine
confidence in using biomedical literature and databases
awareness of challenges of contemporary medicine: epidemic and complex character of most common diseases
awareness of progress and cutting edge application of chemistry in drug design, delivery and in analytical and imaging biomedicine
developing the custom for systematic reading of research literature, due to following rapid developments in biomedical sciences: prerequisite for successful chemist
confidence in using graphics programmes, manipulation and analysis of macromolecular structures

Topics

An Introduction to Chemotherapy, Drug Metabolism and Delivery

Initially this set of lectures will give an overview of the historical development of medicinal chemistry and chemotherapy. Focus will then be on the way in which a pharmaceutical interacts with the human body - the problems this can cause, and the opportunities it can provide for more efficient therapy via targeted drug delivery.T.

Introduction to the Molecular Basis of Diseases

This set of lectures will focus on an explanation of some key molecular aspects of human physiology. It will introduce general classification of diseases (bacterial/viral infections, genetic/complex diseases). This course is a concise survey of the main types of genetic diseases, fundamentals of immune responses, and infections, building the basic biomedical background.

Cancer Chemotherapy

An exploration of current (and potential) cancer therapeutics. This will include well-established drugs that act on DNA (DNA alkylating agents, cross linkers, intercalating agents), drugs that act on structural proteins (taxol, epothiolones). It will be followed by survey of modern approaches in development of new cancer drug targets in the context of expanding hallmarks of cancer. Molecular challenges in a successful cancer eradication will be discussed.

Molecular Aspects of Complex Diseases

The first part will cover: the interlink of the classical hormone:membrane receptor (insulin and Insulin-like Growth Factor (IGF)) signalling, the impact of common switches in signalling pathways for treatment of diabetes, carcinogenesis of insulin, insulin alternatives to anti-diabetic drug targets (nuclear receptors (anti-obesity), metmorfin (oral anti-diabetics)), importance of insulin/IGF in cancer development. Secondly, the in-health/disease role of an alternative regulation of cell-cell communication (hormone=transcription factor), and its clinical modification will be discussed on examples of nuclear receptors (NR). Impact of protein aggregation in disease (Alzheimer, Huntington’s) will be presented. Some aspects of health maintenance (arteriosclerosis, blood pressure) will be covered.

Modern Approaches to Drug Discovery

This module will provide an understanding of the contribution chemical methods and thinking make to the drug discovery process, including target identification, hit identification and lead optimisation. The target-oriented approach to therapeutic intervention will be illustrated with examples from the molecular and cell biology (influenza, HIV, diabetes, obesity, Alzheimer’s and cancer). The examples will also show how a broad range of chemical, biological, structural and computational techniques are being applied in drug discovery. A recurring theme is the need for an understanding of the required properties for a drug molecule. This includes an appreciation of the biological processes that determine ADME and toxicity properties and the types of assays that are used to monitor these.

Metals in Medicine

This part of the module provides an introduction to Medicinal Inorganic Chemistry, an emerging new area of chemistry. The field has been stimulated by the success of cisplatin, still one of the best-selling anti-cancer drugs. Topics include recent developments relating to platinum anticancer agents and other established metallodrugs, such as gold-containing anti-arthritic drugs. In addition, clinically useful ion chelators for the treatment of heavy metal poisoning, iron overload and neuro-degenerative disorders, such as Alzheimer’s or Parkinson’s disease, will be discussed. The focus of the final part of the course will be radiodiagnostic and radiotherapeutic isotopes and the development of MRI contrast agents.

Prerequisites

Chemistry Core Modules 1- 4

Department of Chemistry