30 Questions
What is the biological function of DNA topoisomerases?
Methylating deoxyuridine monophosphate to give dTMP
What is the essential role of folinic acids in the synthesis of thymine and purine bases?
Catalyzing DNA synthesis
How do classical antifolates differ from nonclassical antifolates?
Presence of glutamic acid side chains vs. presence of lipophilic substituents
Why does Aminopterine have a stronger affinity to enzymes compared to natural substrate folic acid?
Additional hydrogen bonds due to replacing (- NH2 ) group with (=O)
What is the main consequence of DHFR inhibition?
Blockage of DNA synthesis
Which statement about 5-Fluorouracil (5FU) is correct?
It is a thymidylate synthase inhibitor
What is the lead structure of Topoisomerase I inhibitors?
Camptothecin
How does Topoisomerase I work to release supercoiled tension in DNA?
By breaking one DNA strand and rotating it around the enzyme
Which chemical modification was done to improve the water solubility of camptothecin, resulting in topotecan?
Addition of hydroxyl and dimethylaminomethyl substituents
What is the mechanism of action of camptothecin derivatives like irinotecan in inhibiting Topoisomerase I?
Stabilizing the cleavable DNA-enzyme complex
What is the active metabolite of irinotecan, a derivative of camptothecin?
SN-38
Which type of cancer is topotecan, a derivative of camptothecin, used to treat?
Ovarian cancer
What is the primary reason for the absence of dTMP in the fluorinated ternary complex?
The complex cannot breakdown due to the stable C5-F bond
Which type of DNA topoisomerase enzyme breaks both strands and requires ATP for full activity?
Topoisomerase II
What is the significance of the 'cleavable complex' in the action of DNA topoisomerase enzymes?
It is the form of the enzyme during DNA cleavage
What is the main function of DNA topoisomerases in DNA transcription and replication?
Winding and unwinding of supercoiled DNA
What is the primary mechanism by which 5-fluorouracil acts as an anticancer drug?
It inhibits the synthesis of dTMP
What is the significance of the 'topo-isomers' in the context of DNA topology?
They refer to DNA loops with different numbers of twists
What is the role of tyrosine residues in the action of DNA topoisomerase enzymes?
They are involved in the cleavage of DNA
What is the primary mechanism by which DNA topoisomerase enzymes regulate the 3D geometry of DNA?
They regulate DNA supercoiling
What is the primary role of oral prodrugs in the context of 5-fluorouracil treatment?
They bypass the need for intravenous administration
What is the primary role of DNA topoisomerase enzymes in DNA transcription?
They facilitate DNA relaxation
What is the mechanism of action of 5-FU in inhibiting DNA synthesis?
Acts as a suicide substrate for thymidylate synthase
Why does 5-FU show selectivity for cancer cells over normal skin cells?
Presence of fluorine atom accelerates formation of ternary complex in cancer cells
Which step in the dTMP synthesis pathway involves the breaking of the imidazolidine ring and release of N10 from the co-factor?
Step 3
Why does the fluorinated ternary complex formed by 5-FU prevent the breakdown into dTMP?
Fluorine atom stabilizes the C5 alkene bond
What is the primary target of methotrexate's mechanism of action?
Thymidylate synthase enzyme
In what way does methotrexate differ from aminopterine in its pharmacokinetic properties?
Affinity to enzyme
What role does co-factor N5, N10-methylene FH4 play in the dTMP synthesis pathway?
Abstraction of a proton from C5 position
What attribute of C6 position on FdUMP makes it more electrophilic than the normal substrate?
+I effect of fluorine atom
Explore the rationale behind using antimetabolites like 5FU and methotrexate in cancer treatment, as well as the modulation of drug treatment methods. Learn about DNA topoisomerases, their biological function, and their significance as targets for developing cancer drugs. Delve into the mechanism of action of topoisomerase inhibitors in anticancer therapies.
Make Your Own Quizzes and Flashcards
Convert your notes into interactive study material.
Get started for free
