DNA Intercalating Agents Flashcards
Name the 5 anthracycline antibiotics. What major mechanistic class do they belong to?
Daunorubicin, doxorubicin, epirubicin, idarubicin, and mitoxantrone. DNA intercalating agents.
Name the 2 DNA intercalating agents that are not anthracyclines.
Dactinomycin/Actinomycin D and Bleomycin
Name the DNA intercalating agent that interferes with DNA-dependent RNA polymerase by intercalating G-C pairs.
Dactinomycin/Actinomycin D
Name the DNA intercalating agent that is derived from copper-chelating peptides and can induce both single- and double-stranded DNA breaks.
Bleomycin
From what microbe were the DNA intercalating agents derived?
Streptomyces
What is the common MO for all the “anti-tumor antibiotics”, and are they cell cycle specific?
DNA intercalating, CCNS
Describe 3 ways DNA intercalating agents fight cancer, without using the word “intercalate”
block DNA/RNA synthesis, cause DNA strand breaks, and interfere with cell replication
What DNA intercalating agent is used to treat pediatric tumors like Wilms’ tumor, rhabdomyosarcoma, and Ewing’s sarcoma, as well as choriocarcinoma (placenta)?
Dactinomycin/Actinomycin D
What is a major side effect of treating pediatric tumors with dactinomycin?
Hematopoietic suppression with pancytopenia
Daunorubicin, doxorubicin/adriamycin, epirubicin, and idarubicin all have what major side effect, and what drug can protect against this effect?
Cardiotoxicity; dexrazoxane is cardio-protective
What 2 anthracyclines are used only to treat AML?
Daunorubicin and idarubicin
Which anthracycline has the broadest spectrum of clinical use, including for sarcomas, breast and lung carcinomas, and malignant lymphomas?
Doxorubicin
What 2 cancers is epirubicin used to treat?
Metastatic breast cancer and gastric cancer
Name the DNA intercalating anthracycline that has the least cardiotoxicity.
Mitoxantrone
Epirubicin is used in the combo regimen FEC to treat what kind of cancer?
Breast cancer (metastatic)
What 2 diseeases is mitoxantrone used to treat?
AML and late-stage multiple sclerosis
Besides intercalation, what is another mechanism by which the anthracyclines cause DNA damage?
They donate electrons to oxygen, forming ROS (reactive oxygen species) like superoxide, hydrogen peroxide, and hydroxyl radicals
What are 3 characterically toxic side effects of bleomycin?
Pulmonary toxicity (fibrosis), cutaneous toxicity (hyperpigmentation, hyperkeratosis, erythema), and hyperthermia
In which DNA intercalating agent is myelo- and immunosuppression the least pronounced, making it a good drug to use in combination regimes like PEB and ABVD?
Bleomycin
Name 3 types of cancer that bleomycin is often used to treat, and the combination regimens associated with 2 of those cancers.
Testicular tumor (PEB), Hodgkins lymphoma (ABVD), and squamous cell carcinoma
