title: Novel DNA groove binding alkylators: design, synthesis, and biological evaluation.
abstract: A group of oligopeptides has been synthesized that are structurally related to the natural antiviral antitumor agents netropsin and distamycin but which bear alkylating functions. Cytostatic activity against both human and murine tumor cell lines as well as their in vitro activity against a range of viruses is reported. The biological activity of these agents is discussed both in terms of their alkylating reactivity and of their structural differences. The incorporation of alkylating moieties into these minor groove DNA binders results in up to 45-fold increase in cytostatic activity compared with netropsin and up to 18 times the activity of distamycin.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Krowicki
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: R A
authors.initials: RA
authors.lastname: Newman
authors.forename: J W
authors.initials: JW
authors.lastname: Lown
mesh_terms: D000477:Alkylating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004214:Distamycins / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009429:Netropsin / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000477:Alkylating Agents; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004214:Distamycins; D009842:Oligopeptides; D009429:Netropsin; D004247:DNA