DDT 10 - Chemotherapy drugs (mode of action) II Flashcards
alternative to chlormethine
chloroambucil
melphalan
estramustine
uracil mustard
describe chloroambucil and name their properties
Aromatic ring is electron withdrawing
Lowers nucleophilic strength of nitrogen
Less reactive alkylating agent
Less side reactions and less toxic
describe properties of mephalan
Aromatic ring is present
Less reactive alkylating agent
Mimics amino acid phenylalanine
Transported into cells by transport proteins
urethran
more hydrophic can pass through membrane through passive diffusion
steroid is hydrophobic
urethrane group is draws electrons
uracil ring
Uracil ring is electron withdrawing
Less reactive alkylating agent
Mimics a nucleic acid base
Concentrated in fast growing cells
effect of DNA Alkylation
Alkylated guanine prefers enol tautomer
Alkylated guanine is hydrogen bond
donor / acceptor / donor
pro drug alkylating anti-cancer
pro drug - have to be activated
e.g Cyclophosphamide oxidised by cytochrome P450 enzyme
nitrosoureas - desompose in the body to form activating agent
how does busulfan a DNA alkylating agent - cause interstrand crosslinking
SN2 reaction
describe the mechanism of the interstrand cross linking of busulfan
electron from nitrogen in guanine base pair moves to C in busulfan
with the help of Mesylate (MeSO3 - a good leaving group) electron from Nitrogen in the Cytosine in the other end of the DNA strand to C then electron from C busulfan moves to O in busulfan
mesylate helps form the cross link
mitomycin C
Prodrug activated in the body to form an alkylating agent
One of the most toxic anticancer drugs in clinical use
Mode of action is via DNA alkylation
where does CC1065 bind to and is it more or less active than cisplatin
Naturally occurring agent
Binds to minor groove of DNA
Alkylates adenine bases
1000 times more active than cisplatin in vitro
oestrogen antagonist
Agents that antagonise the action of oestrogens are of interest
for the treatment of oestrogen dependent breast cancer
example of oestrogen antagonist
tamoxifen -used to treat estrogen hormone dependant breast cancer
17-Beta Estradiol
17β-Estradiol is a steroid hormone
that promotes the growth of certain tissues
how does tamoxifen treat hormone dependent breast cancer
binds to the estrogen receptor binding site without fully activating the receptor and prevents 17β-estradiol from binding
antimetabolites
are compounds that prevent the biosynthesis of normal cell metabolites
example of antimetabolites
5-Fluorouracil (5-FU)
principle of anti metabolites
Structurally designed compound based on the experimental observation that some tumour cells preferentially use uracil for the synthesis of the DNA base thymidine using a biosynthetic pathway not used by normal cells
monoclonal antibodies
produced for several tumour
associated antigens and can act to activate the body’s immune
response to direct killer cells against the tumour.
why are able to use monoclonal antibodies
Cancer cells have altered plasma membranes that contain
distinctive antigens which are over expressed
when compared to normal cells.
what type of cancer does monoclonal antibodies treat/
breast cancers
colorectal cancers
lymphomas
example of monoclonal antibody
herceptin
rituximab
what does herceptin target and why
which targets the HER-2 growth factor receptor which is over expresses on 25% of breast cancers.
what type of cancer does herceptin treat?
treatment of HER-2 positive metastatic breast cancer in combination with the mitotic inhibitor paclitaxel (targets tubulin)
rituximab is against what protein?
CD20 found on the surface of immune system B cells
rituximab is used to treat what kind of cancers
used to treat diseases which are characterized by excessive numbers of B cells or dysfunctional B cells
This includes many lymphomas and leukaemias
Combination therapy - R-CHOP
one of the more widely used combination chemotherapy regimens.
R-CHOP used for what type of cancer?
approved R-CHOP as a first line treatment
for non-Hodgkin’s lymphoma (NHL), B-cell NHL subtypes, including follicular lymphoma,
mantle cell lymphoma, Burkitt’s lymphoma
what does a course of R-CHOP look like?
R-CHOP involves 6 to 8 treatments separated by 21 days with
examples of alkylating anti-cancer drugs of chlormethine analogues
chlorambucil
melphalan
urethane
uracil mustard
list pro-drug alkylating anti-cancer
cyclophosphamide nitrosoureas: lomustine and carmustine busulfan mitomycin C CC1065 Tamoxifen
name 2 Monoclonal antibodies
Herceptin used w/ Paclitaxel
Rituximab
