Anti-cancer drugs targeting DNA Flashcards
Metallating and Alkylating agents:
Highly — species, looking for — sites to attack to form — bonds with the — in —
This prevents — and —
These have — side-effects.
They bind in the — groove of the DNA
Both types cross-link DNA by — bonding to the — on base pairs.
Binding of nucleic acid base pairs results in — and —
Distortion of DNA prevents — by — proteins, leading to – damage. As the — and — is slowed, the growth of the — is —
2 — sites on an anticancer drug can cause — and — cross-linking. Preference for linkage sites is dictated by drug —/–
electrophilic nucleophilic covalent bases DNA replication + transcription toxic major covalently nitrogen miscoding distortion excision HMG permanent transcription replication tumour slowed electrophilic interstrand intrastrand chemical structure
Metallating agents:
The prodrug is administered —, it is converted to the DNA metallating agent in lower — concentrations in cells.
There is extensive drug development in process to reduce —/— and to develop the ability to be able to deliver the drug —
intravenously
chloride
side-effects
orally
Alkylating agents: Chlormethine (a nitrogen mustard)
Chlormethine is highly — with — side-effects
This is a — compound for many, less toxic mustard —
The — group has a positive — effect, it promotes the loss of the — group.
reactive toxic lead, derivatives methyl inductive chloride
Less toxic chlormethine analogues:
the — withdrawing — lowers the — strength of nitrogen making the drug less — with less side-effects and less —
It mimics pHAla and is carried into cells by — proteins.
electron, ring, nucleophilic
reactive, toxicity
transport
Uracil Mustard:
Uracil ring is —/—, so is a less reactive — agent.
It mimics a —/— base and concentrates in —/— cells
electron withdrawing
alkylating
nucleic acid
fast growing
Estramustine:
The alkylating group is attached to —
It is — and capable of crossing —/—
The urethane group is —/— and reduces the — strength of —
oestradiol hydrophobic cell membranes electron withdrawing nucleophilic nitrogen
Cyclophosphamide:
Most commonly used —/—
—/— and orally — prodrug
The acrolein is associated with —
alkylating agent
non-toxic
active
toxicity
Nitrosureas decompose to — agent and — agent.
The — agent causes — links on – or – links
The isocyanate, which is a — agent reacts with — on proteins and may inactivate DNA — enzymes
alkylating carbamoylating alkylating interstrand GG or GC carbamoylating Lys repair
Busulfan causes — cross-linking
the — group withdraws electrons, so the adjacent — is subject to — attack by — bases
interstrand sulphonate carbon nucleophilic DNA
Dacarbazine- A diazine
It is a — which is activated by — in the —-
it decomposes to form the —
It alkylates — groups
Dacarbazine is the lead for the triazine prodrug —
This is the primary drug for malignant —
This type of tumour accounts for –% of all primary – tumours.
Treatment regime is for initital —, then — and —
prodrug oxidation liver methyldiazonium guanine Temozolomide Astrocytomas 60 surgery radiotherapy chemotherapy
Intercalating agents:
Antibiotics- Dactinomycin:
Intercalates via — groove of DNA —/—
prevents — of the helix
Blocks — and blocks the DNA-dependent —/—
Adriamycin:
Provides extra binding to —/— backbone by —
Intercalates via — groove of — helix
It is also a — poison, it blocks the action of this by stabilizing the —/— complex
Minor, double helix unzipping transcription, RNA polymerase sugar-phosphate NH3 Major DNA topoisomerase DNA/enzyme
Chain Cutters: Calicheamicin: antitumour agent
A — attack on the — chain starts a — process.
This interacts with DNA to generate a DNA —,
which reacts with —, resulting in —/—
The diradical abstracts — atoms from the — of the DNA, which leads to strand —. This happens when a reaction with hydrogen peroxide gives FeIII and hydroxyl radicals
nucleophillic trisulphide rearrangement Diradical oxygen chain cutting hydrogen deoxyribose scission
Bleomycins:
Highly active against —, —, and — cancer
Single and double strand cleavage of DNA with several reduced — ions
The Bithiazole DNA —/— locks BLM into the — groove
The carbohydrate domain uses — bonds to hold the BLM to the —/— of the DNA
The metal binding domain binds to —
5 atoms of BLM bind the metal
head, neck, testicular metal binding domain minor H sugar phosphate Fe
Lungs and skin have low levels of —/—, so have a higher — and — to BLM.
BLM hydrolase
sensitivity
toxicity
