Medicinal Chemistry Chapter 9 PDF - Drugs Acting on DNA

Chapter 9 I Identify and categorize drugs acting on DNA into groups according to the mode of action. Intercalating agents, Topoisomerase poisons, Alkylating agents, metallating agents, Chain cutters, Chain terminators intercalating agents : compounds that...

Chapter 9 I Identify and categorize drugs acting on DNA into groups according to the mode of action. Intercalating agents, Topoisomerase poisons, Alkylating agents, metallating agents, Chain cutters, Chain terminators intercalating agents : compounds that contain planar or heteroaromatic features that allow it to slip between the base pairs of the DNA double helix Some drugs will go through the minor or major groove of the helix inserted the rings of held Once the drug are. , there VDW interactions with the through base pairs above and below. Some can interact withthe charged phosphate groups of the DNA backbone. Once inserted and /or the drug can prevent replication transcription leading to cell death ex : proflavine planar tricyclic system. antibacterial used dangerous for systemic use. as a topical because it destroys the DNA preventing replication n. dactinomycin (anti-cancer) two cyclic pentapeptides. : flat tricyclic heteroatom structure. extra binding to sugar phosphate backbone by cyclic peptides. intercalates between double groove of DNA minor helix interactions between prefers guanine-cytosine. prevents unwinding of DNA · blocks transcription by blocking DNA-dependent RNA polymerase.  topoisomerase poisons-non-intercolating : Stabilize the complex between DNA and topoisomerase enzymes. prevents DNA Strand I the rejoining of the does Not intercalate (go in between) DNA helix used anti-cancer as agents chain causes cutting ex : camptothecin extracted from a chinese bush in 1966 Stabilizes complex between DNA and topoisomerase I breaks accumulate in single-strand the chain irreversible double-strand breaks occur during transcription alkylating agents : contain highly electrophilic groups form S covalent bonds to nucleophilic groups DNA in prevent replication and transcription useful anticancer agents can cause interstrand and infrastrand crosslinking if two electrophilic groups present alkylation of nucleic acid bases can result in miscoding N  metallating agents : discovered that bacterial cell division was inhibited by a product of the electrolysis from platinum electrodes neutral inactive molecule acting as a prodrug platinum covalently linked to chloro substituents once in cell water displaces the chloro substituents creates a positively charged species that can act as a metalating agent Chain Cutters : cut the strands of DNA and the prevent enzyme DNA ligase from repairing the damage m ay act by creating radicals in the DNA structure radicals then react with oxygen to form peroxy and the species , DNA chain fragments calicheamiciny : Ex antitumor bacteria agent from - DNA binds groove of - to major diradical; DNA diradical -generates DNA reacts with chain oxygen , results in cutting chain terminators: drugs that act "false substrates" and are incorporated as into a growing DNA Strand during replication these drugs "mistaken" for nucleotide are triphosphates Must 3 conditions satisfy they must be recognized by the DNA template must triphosphate to allow them to contain a group undergo addition to the the same enzyme catalyzed chain as the blocks normal building their structure must make the addition of more nucleotides impossible