Antibiotics Cancer Flashcards
Anthracyclines and Anthracenediones?
Doxorubicin, Idarubicin, Daunorubicin, Epirubicin, Valrubicin, and Mitoxantrone
(Do, I, Dance, E,V,M)
Antibitotics
Dactinomycin, Bleomycin, Mitomycin
Antineoplastic Antibiotics Vs. Antibitoics?
Antineoplastic ABX act on tumerous or cancer cells while the other on bacterial cells.
-Microbial origin
What gives Dactinomycin their biological activity and cytotoxicity?
Binding to double-helical DNA
Formation of a Dactinomycin-DNA complex….
stability sufficient to block the transcription of DNA by RNA polymerase
Phenoxazone ring intercalates between _____
adjacent guanine-cytosine base pairs of DNA
Dactinomycin is much more effective in ______
blocking transcription of RNA due to the DNA-dependent RNA polymerases being much more sensitive.
Dactinomycin causes single strand breaks in DNA due to ?
Free-radical intermediate (topoisomerase II)
Treatment for Rhabdomyosarcoma and Wilms Tumor in children?
Dactinomycin + Vincristine and Cyclophosphamide with surgery and radiotherapy
(Do, Children, Vibe)
Choriocarcinoma treatment?
Dactinomycin and MTX
(Chronic——>D, M)
Dactinomycin is extremely _____?
corrosive to soft tissues
What are your naturally producing anthracyclines?
Idarubicin, Epiruubicin, Doxorubicin, Daunorubicin
(Do, I, Dance, Easy)
Which anthracycline is a semisynthetic analogue of Doxorubicin?
Valrubicin
Mitoxatrone is a synthetic anthracenedione derivative of ________?
Topoisomerase II Inhibitor
Anthracyclines and Anthreacenediones MOA?
Intercalate with DNA, directly affecting transciption (RNA) and replication (DNA)
main important activity of anthracyclines is to?
form a heterotrimeric complex with topoisomerase II and DNA
What is topoisomerase II for?
essential for DNA replication and repair
-produces double strand breaks at the 3’ phosphate backbone, allowing uncoiling of supercoiled DNA)
Topoisomerase II + Anthracyclines
make a ternary complex which inhibits reliagtion of broken DNA, leading to apoptosis
Quinone moieties of anthracyclines can?
form radical intermediates that react with O2 to produce superoxide anion radicals, this attacks DNA (oxidizes) and leads to damage and apoptosis
Resistance to anthracylcines?
-decreased/mutation of topoisomerase II
-Increased glutathione
-Enhanced ability to repair DNA strand breaks
Anthracyclines cross the BBB?
No they do NOT
Anthracyclines cause?
Cardiomyopathy (long term) and congestive heart failure (chronic, dose related)
Doxorubicin is effective in which cancer?
malignant lymphoma when used in combo with other agents
Bleomycin MOA?
generates free radicals, oxidative damage to the deoxyribose of thymidylate and other nucleotides leading to single and double stranded breaks in DNA
