Medicinal Chemistry Flashcards
Why is cancer a killer?
Tumours grow in confined space and destroy normal tissue by crowding.
It causes immune deficiency increasing rate of infections.
Tumours produce hormone like chemicals which disrupt normal metabolic functions.
Invasion causes haemorrhage and infection.
Tumours metastasise to distant organs (e.g. bone, liver, brain, lungs) and destroy tissues.
Factors that influence cancer survival?
The type of cancer - some are more treatable than others.
Genetics of individual tumour - some are resistance to treatment, some are responsive.
Diagnosis and treatment time.
Best medical practice - new drugs, techniques and experimental therapies improve patients’ outcomes.
What are alkylating agents role in medicinal chemistry, and what effects may occour when they bind?
Alkylating agents cause cell death - they do this by interacting with DNA during cell synthesis.
A biological nucleophile binds to the alkylating agent.
They bind to DNA - leads to miscoding during replication (e.g. G-C to G-T shift). Causes DNA damage and cell death.
How do Vinca Alkaloids work?
Vinca alkaloids act during the M-phase of the cell cycle (cell division).
They depolymerise microtubules and destroy mitotic spindles by removing a ‘cap’ - a circle of alpha and beta ball shaped tubluin heterodimers
This leaves the dividing cancer cells blocked in mitosis with condensed chromosomes.
The leaving tubulin dimers bind to Vinca Alkaloids and form a ‘wall’ of aggregates - this leads to depolymerisation.
How does Vinblastine relate to Vinca Alkaloids?
Vinblastine binds to the high-affinity sites at the + end of the microtubule to suppress microtubule dynamics.
The binding of vinblastine to soluble tubulin is rapid and reversible.
What do Taxols do?
Hyperstabilises the structure of tubilin.
It binds to the β subunit of tubulin and causes the protein to lose its flexibility, taxol prevents a cell from dividing.
Cells have two DDR (DNA Damage Response Pathways) A and B. What are the pathways?
A cell has two pathways A and B - if no pathways are lost - the daughter cell is and A B daughter cell that survives.
If one pathway (B) is eliminated, the daughter cell then just has pathway A. With one pathway genome instability occurs, which could lead to the evolution of a cancer cell.
Addition of an inhibitor targeting the second pathway (A) leads to cell death.
What examples are there of water soluble derivatives?
Any version of a Nitrogen in a 6 membered ring as a side chain, can have Oxygen in it as well.
What is PARP?
PARP (Poly ADP-Ribose Polymerase) is used to repair DNA.
It has a major role in DNA base-excision repair pathway (BER) and it utilises NAD+ as a substrate, by binding to DNA, rather than as a coenzyme to repair DNA.
What is the Phosphodiester Bond?
The Phosphodiester Bond (PO4, one Oxygen double bond) is the bond that holds the sugar-phosphate components of the DNA molecule together.
The 3′- carbon is linked with the 5′- carbon in the DNA via the phosphodiester bonds.
What are topoisomereases?
Topoisomerases sorts out winded DNA and the tension it causes. It wraps around DNA and makes a cut, allowing DNA to spin, then reconnects it.
What is oncology?
Oncology, or hormonal therapy, is the manipulation of the endocrine system through administration of specific hormones.
eg Steroid hormones, or drugs which inhibit the production or activity of such hormones.
How does Tamoxifen work?
Acts as an estrogen, antiestrogen or mixed agonist/antagonist, depending on target organ.
It binds competitively to the steroid binding site, on the estrogen receptor (ER) - with ER then losing a stabilising protein.
ER binds then to DNA at the estrogen response element (ERE) - the complex is weakly active.
What are Protein Kinase Enzymes?
Kinase enzymes transfer the terminal phosphate (PO4-) of ATP onto an amino acid with a -OH group (tyrosine, serine or threonine).
They govern many processes within cells including the cell cycle and signalling from the cell surface to the nucleus.
What is the Human Epidermal Growth Factor Receptor (HER) and its Receptor (EGFR)?
Human Epidermal Growth Factor Receptor (HER) are signalling pathways with dysregulation of them leading to growth of cancer cells.
The HER family consists of 4 structurally related receptors: HER1 (EGFR), HER2, HER3, and HER4.
EGFR plays a key role controlling two major cellular signalling pathways (cell proliferation/growth and survival).
EGFR is over-expressed or mutated in several cancers.
What is VEGF (Vascular Endothelial
Growth Factor)?
VEGF is when tumours secrete a
signalling protein – VEGF.
The VEGF then binds to receptors (VEGFR) on on nearby blood vessels.
Bonding to receptors triggers the formation of new blood vessels, which help the tumour grow and spread.
What is a Primary pathogen?
Cause disease as a result of their presence or activity within healthy host, and their intrinsic virulence.
What is an Opportunistic pathogen?
Cause an infectious disease in a host with depressed resistance or unusual access to the inside of the body (e.g. trauma)
What is a mixed infection?
Caused by more than one bacteria.
What does Iatrogenic, Nosocomical and Zoonotic mean?
Iatrogenic - Tramsitted from health care worker to patient
Nosocomical - Hospital acquired infection
Zoonotic - Pathogen has jumped from animal to human
What is the structure of a bacteria?
Has a capsule with a cell wall. Space in the middle is plasma membrane.
Inside has cytoplasm, ribosomes, plasmid DNA, nucleoid.
No nucleus.
