Distamycin analogues with enhanced lipophilicity: synthesis and antimicrobial activity.
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.
Khalaf
Abedawn I
AI
Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland, U.K.
Waigh
Roger D
RD
Drummond
Allan J
AJ
Pringle
Breffni
B
McGroarty
Ian
I
Skellern
Graham G
GG
Suckling
Colin J
CJ
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
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D004214:Distamycins; C050796:distamin; D004247:DNA