Nucleic Acids & Other Drug Targets Flashcards
What are nucleic acids commonly targeted by drugs?
DNA and RNA, especially in antibacterial and anticancer therapies.
What are the main drug classes targeting nucleic acids?
Intercalating agents, topoisomerase poisons, alkylating agents, chain cutters, and chain terminators.
What are intercalating agents?
Planar or heteroaromatic compounds that insert between DNA base pairs, preventing replication and transcription.
How do intercalating drugs bind DNA?
They approach via the major or minor groove and insert between base pairs, stabilized by van der Waals forces.
What is an example of an intercalating drug?
Proflavine (antibacterial) and Doxorubicin (anticancer, also a topoisomerase poison).
What are topoisomerase poisons?
Drugs that stabilize the transient cleavable complex formed between DNA and topoisomerases, preventing re-ligation.
Give an example of a topoisomerase poison.
Doxorubicin (topoisomerase II poison) and Camptothecin (topoisomerase I poison).
What are alkylating agents?
Highly electrophilic drugs that form strong covalent bonds with nucleophilic sites on DNA bases.
What is the effect of alkylating agents on DNA?
They create cross-links within or between DNA strands, preventing replication and transcription.
What is a key limitation of alkylating agents?
Poor selectivity; they can also react with proteins, causing toxicity, mutagenicity, and carcinogenicity.
Give examples of alkylating agents.
Nitrogen mustards, nitrosoureas, and busulfan.
What is a metallating agent?
A compound that interacts with DNA through metal coordination, leading to DNA damage.
Give an example of a metallating agent.
Cisplatin, which forms intrastrand cross-links between guanines, disrupting DNA structure.
What are chain cutters?
Drugs that introduce breaks in DNA strands, preventing DNA ligase from repairing the damage.
How do chain cutters work?
They generate radicals on the DNA structure, which react with oxygen to form peroxy species, leading to fragmentation.
What are chain terminators?
Drugs that mimic normal DNA bases but prevent further chain elongation during replication.
Give an example of a chain terminator.
Aciclovir, which is phosphorylated into an active form and incorporated into viral DNA.
How do drugs interact with RNA?
They bind to ribosomes to inhibit bacterial protein synthesis or use antisense therapy to block mRNA.
What is antisense therapy?
A treatment using oligonucleotides to block the coded messages carried by mRNA.
What are transport protein targets?
Proteins that normally transport molecules, which can be blocked by drugs to alter neurotransmitter levels.
Give an example of a drug targeting transport proteins.
Cocaine and tricyclic antidepressants, which prevent neurotransmitter reuptake, increasing synaptic levels.
What are structural protein targets?
Proteins forming essential cellular structures, such as viral capsids and microtubules.
How do antiviral drugs target structural proteins?
By preventing uncoating of viral capsids, blocking viral replication.
How do anticancer drugs target structural proteins?
They inhibit microtubule polymerization and depolymerization, disrupting cell division (e.g., colchicine, vinca alkaloids, paclitaxel).
What are biosynthetic building block inhibitors?
Drugs that block essential biosynthetic pathways in bacteria, preventing cell wall formation.
Give an example of a biosynthetic inhibitor.
Vancomycin, which caps peptidoglycan building blocks, preventing bacterial cell wall synthesis.
What are protein-protein interaction inhibitors (PPBIs)?
Drugs that prevent protein-protein associations, often used in cancer and neurodegenerative diseases.
How are antibodies used as drug targets?
They selectively bind extracellular proteins, such as in immunosuppressive therapy (e.g., daclizumab).
What are aptamers?
Short oligonucleotides that bind to specific protein targets with high selectivity.
How do drugs target lipids?
By disrupting lipid membrane structure, altering cell function.
How do general anesthetics target lipids?
They interact with cell membrane lipids, altering membrane properties and conduction.
What are tunneling molecules?
Antifungal agents that create channels in fungal cell membranes, causing ion leakage and cell death.
Give an example of a tunneling molecule.
Amphotericin B, which forms pores in fungal membranes.
What are ion carriers?
Molecules that transport ions across membranes, disrupting ionic equilibrium.
Give an example of an ion carrier.
Valinomycin, which transports potassium ions, disrupting cell function.
