title: Distamycin analogues with enhanced lipophilicity: synthesis and antimicrobial activity.
abstract: Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or aliphatic heterocylic aminopropyl substituents. The ability of these compounds to bind principally to AT tracts of DNA has been evaluated using capillary zone electrophoresis. Significant antimicrobial activity against key organisms such as MRSA and Candida albicans is shown by several compounds, especially those containing a thiazole. Moreover, these compounds have low toxicity with respect to several mammalian cell lines.
authors.affiliation: Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland, U.K.
authors.forename: Abedawn I
authors.initials: AI
authors.lastname: Khalaf
authors.forename: Roger D
authors.initials: RD
authors.lastname: Waigh
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Drummond
authors.forename: Breffni
authors.initials: B
authors.lastname: Pringle
authors.forename: Ian
authors.initials: I
authors.lastname: McGroarty
authors.forename: Graham G
authors.initials: GG
authors.lastname: Skellern
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Suckling
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000737:chemistry; D004214:Distamycins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019075:Electrophoresis, Capillary; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D004214:Distamycins; C050796:distamin; D004247:DNA