DDT 9 Chemotherapy drugs Flashcards
fundamental techniques to treat cancer
surgery
radiation therapy
chemical based approach
purpose of chemotherapy
Cure a specific cancer
Reduce the size prior to surgery
Sensitize tumour to radiation therapy
Destroy small metastases after surgery
what is chemotherapy useful for?
useful for eliminating cancers that are relatively small in size.
why are chemotherapy not used for large cancers
large cancers are not perfused by blood and thus the inner part may not be accessible to chemotherapeutic agents.
limitation of chemotherapy
the lack of selectivity of the agents for normal versus malignant cells.
assumption in chemotherapy
tumour cells - high metabolism - divide much quicker than normal cells
will uptake more chemotherapy drugs
why are the side effects of chemotherapy, hair loss,depression of
immune system and nausea.
cells that are strongly affected by chemotherapy include
hair cells
bone marrow cells
cells lining the gastro-intestinal tract
mechanism of chemotherapy
topoisomerase inhibitors Alkylating agents Antimetabolites Monoclonal antibodies intercalating agents
topoisomerase function
helps DNA uncoiling for the process of DNA replication and protein synthesis
intercalating agents
can insert into double helix of DNA and distort structure
can inhibit the enzymes involved in replication and transcription processes
Anthracyclines
naturally occurring antibiotics isolated from bacteria
have anti-cancer properties - bind to DNA structure
doxorubicin is isolated from what
streptomyces peucetius in 1967
what type of cancer does doxorubicin target
broad range of solid tumours
how does doxorubicin act against cancer
binds into DNA and acts as a topoisomerase II poison
stabilises the complex formed between DNA and topoisomerase II
Excessive no. of stabilised DNA-enzyme complexes
triggers apoptosis.
how does doxorubicin bind to DNA?
bind to CG or GC base pair to form a buckle
distort DNA structure and prevent Van der Waals forces
stabilized by - H bonding and aromatic pi bonding
Dactinomycin is isolated from what
S. parvullus
what does dactinomycin contain
3 fused aromatic rings
Two identical pentapeptide side chains
what tumour does the dactinomycin target?
pediatric solid tumours
where does dactinomycin bind to DNA and what holds the drug in place?
between GC base pairs
favours intercalation between 2 G bases on diff. strands
Held by aromatic pi stacking interactions between tricyclic ring and
tubulin
strucutral protein - crucial to cell division
acts as building block for microtubules - polymerised and depolymerised in cell division
how do drugs block the process of microtubules
Drugs can block this process by either binding to tubulin to prevent
polymerization or binding to the microtubules to prevent
depolymerisation
why do anti cancer cells acting on tubulin effective in inhibiting cancerous cell division
cancer cells divide rapidly through mitosis and need microtubules for division
where does vincristine bind to
bind to tubulin inhibiting assembly of microtubule
stops mitosis in metaphase and prevent cell replication
what types of cancers does vincristine work for?
work w/ other drugs for non-Hodgkins lymphoma and childhood leukemia
paclitaxel function
stabilise microtubules - interfere w/ normal breakdown of microtubules
blocks progression of mitosis - triggers apoptosis
features of alkylating anti cancer agents
Drug contains highly electrophilic groups.
They form covalent bonds to nucleophilic groups in DNA (e.g. N-7 of guanine).
This prevent replication and transcription.
Useful anti-tumour agents.
function fo alkylating anti cancer agents
Used as anticancer agents
Can cause interstrand and intrastrand crosslinking if two electrophilic groups are present
toxic side effect of alkylating anti cancer agent
Toxic side effects due to non-selective alkylation
e.g. alkylation of proteins or alkylation of DNA in rapidly dividing non-cancerous cell
what can alkylation of nucleic acid lead to?
Alkylation of nucleic acid bases can result in miscoding
DNA alkylating agent
cause cross linking of intrastrand (within the same strand)
interstrand (between two strands in DNA)
function of chlormethine - an alkylating agent
Causes intrastrand and interstrand crosslinking
Prevents cell replication
Monalkylation of guanine also possible
when was chlormethine first used
Used medicinally first in 1942
chlormethine is an example of what
nitrogen mustard
reaction mechanism of hydroxide/ammonia w/ chloromethane
OH-/NH3 attack the nearest H in the chloromethane - forms methanol/ chloromethine and Cl-
describe in detail the mechanism of the azridine ion from chlormethine to the DNA
chloromethine (Electron in N of chloromethine is drawn to partially positive charge in Cl and moves to C - electron from C moves to Cl) -> aziridine ion
nitrogen bind to corner of molecule
1st chemical mod.: N from DNA strand attaches to C end of Azridine ion
electron from N moves to C near other Cl and electron from C moves to Cl
N from other side of strand attacks the complex
what is the purpose of anti-cancer drugs interfering with microtubule function
to prevent mitosis
how do alkylating agents prevent anti-cancer cells from replicating
interfere with DNA base pairing, leading to strand breaks and stopping DNA replication
Antimetabolites function as an anti-cancer drug
block the formation and use of nucleic acids essential for DNA replication
Monoclonal antibodies function as an anti-cancer drug
recognition of over expressed antigens on cancer cell membrane
what helps stabilise the dactinomycin bound to DNA
DNA bases
Stabilised by peptide hydrogen-bonding to nucleic acid bases of DNA
how does dactinomycin act as an anti-cancer drug
→ interferes with Topoisomerase II,
→ inhibition of replication and transcription
Name chemotherapy drugs that act on tubulin
vincristine
paclitaxel
types of cancer paxlitaxel is used for
ovarian breast lung bladder prostate melanoma oesophageal cancer
